Hypertension

= Htn, Essential Hypertension

1. See Also 1. Hypertension in Children

2. Hypertension in Infants

3. Hypertension in Pregnancy

4. Hypertension in Athletes

5. Hypertension in the Elderly

2. Epidemiology 1. Demographics

1. White Adults in US: 20% are hypertensive

2. Black Adults in US: 30% are hypertensive

3. Of all hypertensives, >50% are over age

65 years

2. Outcomes 1. BEST PREDICTOR TO OUTCOME

VARIES BY AGE 1. Diastolic Blood Pressure best

predictor <50 years

2. SBP and DBP predict outcomes

equally ages 50-59

3. Pulse Pressure best predictor age

>60 years

2. Coronary Artery Disease 1. Hypertension Causes 35-45%

morbidity and mortality

3. Cerebrovascular Accident 1. Relative Risk increases 1.84 for each

10 mmHg DBP

2. Midlife hypertension raises

longterm CVA risk

3. Seshadri (2001) Arch Intern Med

161:2343

4. Alzheimer's Disease 1. Increased SBP in middle age is

predisposing factor

5. Reference 1.

(1995) Lancet 346(8991):1647

2.

Kivipelto (2001) BMJ 322:1447

3. Hypertension Definition 1. See Hypertension Criteria

4. Types 1. Essential Hypertension (Primary

Hypertension)

1. Stage 1-2 (DBP 90-104) in 80%

of cases

2. ACCELERATED MALIGNANT

HYPERTENSION

1. Recent substantial Blood Pressure

increase

2. Associated with retinal vessel damage

1. Retinal Hemorrhages

2. Retinal exudates

3. Papilledema

3. Diastolic Blood Pressure over 140

3. ISOLATED SYSTOLIC HYPERTENSION

1. Systolic Blood Pressure: >160 mmHg

2. Diastolic Blood Pressure: <90 mmHg

3. Risks

1. Coronary Artery Disease

2. Cerebrovascular Accident

4. Onset: 5th decade

5. Affects 11% of those over age 75 years

6. Results from progressive fall in vessel

compliance

5. Causes of secondary

Hypertension 1. See Hypertension Causes

6. Diagnosis 1. See Hypertension Criteria

7. Hypertension Evaluation 1. Hypertension Evaluation History

2. Hypertension Evaluation Exam

3. Hypertension Evaluation Labs

8. Management 1. See Hypertension Management

Hypertension Resources

1. Dash Diet and other lifestyle change handouts 1. http://www.nhlbi.nih.gov/health/public/h

eart/hbp/dash 2. NIH Patient Handout Order Forms (free

for single copy)

1. CvHtnNihPubOrders.pdf

Isolated Systolic Hypertension = ISH

1. See Also

1. Hypertension

2. Epidemiology 1.

Most common type of Hypertension in adults

3. Criteria 1. Systolic Blood Pressure: >140 mmHg (previously >160)

2. Diastolic Blood Pressure: <90 mmHg

4. Complications: Cardiovascular Risk 1. GENERAL

1. Systolic pressure predicts risk better than

diastolic

2. Wide Pulse Pressure best predicts cardiovascular

risk

2. ADVERSE EFFECTS

1. Doubles all cause mortality

2. Triples cardiovascular mortality

3. Increases cardiovascular morbidity 2.5 fold

5. Management 1. USE LOWER ANTIHYPERTENSIVE

DOSAGES

2. FIRST CHOICE MEDICATION: Diuretic 1. Even better benefit in Diabetes Mellitus with ISH

2. Study of 4736 type II diabetics

1. Lower Incidence of cardiac events

1. Lower Incidence of

Cerebrovascular

Accidents

2. Lower Incidence of

Myocardial Infarction

2. Reference

1. Curb (1996) JAMA 276:1886

3. OTHER MEDICATIONS

1. Dihydropyridine Calcium Channel Blocker

2. Long Acting Nitroglycerin

3. ACE Inhibitor

4. Labetalol

Pulse pressure, widened: Excerpt

from Alarming Signs and

Symptoms: Lippincott Manual of

Nursing Practice Series

Pulse pressure is the difference between systolic and diastolic blood pressures. Normally, systolic pressure is about 40 mm Hg higher than diastolic pressure. Widened pulse pressure — a difference of more than 50 mm Hg — commonly occurs as a physiologic response to fever, hot weather, exercise, anxiety, anemia, or pregnancy. However, it can also result from certain neurologic disorders — especially life-threatening increased intracranial pressure (ICP) — or from cardiovascular disorders that cause blood backflow into the heart with each contraction such as aortic insufficiency. Widened pulse pressure can easily be identified by monitoring arterial blood pressure and is commonly detected during routine sphygmomanometric recordings.

Act Now: Ifthe patient’s level of consciousness (LOC) is decreased and you suspect that his widened pulse pressure results from increased ICP, check his vital signs. Maintain a patent airway, and prepare to hyperventilate the patient with a handheld resuscitation bag to help reduce partial pressure of carbon dioxide levels and, thus, ICP. Perform a thorough neurologic examination to serve as a baseline for assessing subsequent changes. Use the Glasgow Coma Scale to evaluate the patient’s LOC. (See Glasgow Coma Scale, page 196.) Also, check cranial nerve (CN) function — especially in CNs III, IV, and VI — and assess pupillary reactions, reflexes, and muscle tone. (See Exit points for the cranial nerves.) The patient may require an ICP monitor. If you don’t suspect increased ICP, ask about associated symptoms, such as chest pain, shortness of breath, weakness, fatigue, or syncope. Check for edema and auscultate for murmurs.

LABETALOL

Pharmacology

Metabolism: liver extensively; CYP450: unknown

Excretion: urine 50% (<5% unchanged), feces 50%; Half-life:

5-8h

Subclass: Beta Blockers

Mechanism of Action selectively antagonizes alpha1-adrenergic receptors; antagonizes beta1- and beta2-adrenergic receptors (selective alpha and non-selective beta blocker)

Hypertension Causes

= Secondary Hypertension Causes, Hypertension Causes in

Children, Hypertension Causes in Adolescents

1. Causes: Secondary Hypertension in Adults

1. MEDICATIONS

1. See Medication Causes of Hypertension

2. PRIMARY ALDOSTERONISM 1. Most common treatable secondary cause

of Hypertension

2. Evaluate as cause in Refractory

Hypertension where Hypokalemia or

borderline low potassium

3. RENOVASCULAR OR RENAL PARENCHYMAL DISEASE

4. PHEOCHROMOCYTOMA

5. CUSHING'S DISEASE

6. HYPERPARATHYROIDISM

7. AORTIC COARCTATION

8. SLEEP APNEA

9. THYROID DISEASE

1. Hyperthyroidism causes systolic Hypertension

2. Hypothyroidism causes diastolic Hypertension

1. Dernellis (2002) Am Heart J 143:718

2. Causes: Secondary Hypertension in age <18 years old

1. SEE HYPERTENSION IN INFANTS

2. Renal parenchymal disease

1. Most common cause in children (up to 70%)

3. Renal vascular disease

4. Aortic Coarctation

5. Endocrine conditions 1. Metabolic Syndrome

2. Pheochromocytoma

3. Hyperthyroidism

6. Essential Hypertension

1. Rare in age <10 years

2. Most common cause in adolescents and

adults

7. Medications 1. See Medication Causes of Hypertension

Hypertension Evaluation

1. Goals 1. Confirm Hypertension (see Hypertension Criteria)

2. Identify associated RISK FACTORS

3. Identify target organ disease

4. Evaluate for secondary Hypertension

2. Evaluation 1. Hypertension Evaluation History

2. Hypertension Evaluation Exam

3. Hypertension Evaluation Labs

3. Monitoring Protocol 1. MILD BLOOD PRESSURE INCREASE

1. Recheck in 1-2 months

2. MODERATE BLOOD PRESSURE INCREASE

1. Recheck in 1-2 weeks

3. SEVERE OR ACCELERATED MALIGNANT HYPERTENSION

1. Immediate Treatment

4. END ORGAN DAMAGE 1. Immediate Treatment

Hypertension Evaluation History

1. History: Past Medical History

1. Onset and severity of Hypertension

2. Average Blood Pressure

2. History: Family History 1. Hypertension

2. Kidney disease

3. History: Medications

1. See Medication Causes of Hypertension

4. History: Habits: 1. Salt intake

2. Fat intake

3. High caloric intake contributing to Obesity

4. Alcohol use

5. Tobacco Use

6. Recreational drugs of abuse

1. Cocaine

2. Methamphetamine

5. History: Lead Exposure Risk

1. Lead paints

2. Printer inks

3. Inhalation risks

4. Postmenopausal women

1. Lead increases due to skeletal lead

mobilization

2. Nash (2003) JAMA 289:1523

6. History: Symptoms of Urinary tract Disease

1. Urinary Tract Infection

2. Nephrolithiasis (or Hypercalcemia)

3. Benign Prostatic Hypertrophy

7. Findings: Evidence of Endocrine Disease

1. Diabetes Mellitus

2. Hyperthyroidism

3. Hypothyroidism

4. HYPERPARATHYROIDISM (HYPERCALCEMIA)

1. Confusion

2. Major Depression

3. Abdominal Pain

4. Nephrolithiasis

5. Constipation

5. CUSHING'S DISEASE 1. Acne Vulgaris

2. Osteoporosis

3. Bone Fractures

4. Glucose Intolerance

6. ALDOSTERONISM 1. Hypokalemia

2. Muscle Weakness

3. Paresthesias

4. Tetany

7. 11-HYDROXYLASE DEFICIENCY 1. Premature virilization in males

2. Masculinization in females

8. 17-HYDROXYLASE DEFICIENCY 1. Failed sex maturation

9. PHEOCHROMOCYTOMA 1. Sweating

2. Tremor

3. Panic

4. Facial pallor

5. Headache

6. Weight loss

8. Findings: Evidence of Neurologic Disease

1. Previous Neurologic disease or symptoms

2. Headaches

3. Confusion

4. Seizures

9. Findings: Evidence of Cardiovascular disease

1. Coronary Artery Disease

2. Congestive Heart Failure

3. Amaurosis Fugax

4. Claudication

5. Renal Artery Stenosis

10. Findings: Evidence of Sleep Disorder

1. Sleep Apnea

2. Exaggerated snoring

3. Inappropriate sleep episodes

_____________

Amaurosis

http://www.bing.com/reference/semhtml/Amaurosis?si

ds=2&q=Amaurosis+fugax&qpvt=Amaurosis+fugax

http://www.bing.com/reference/semhtml/Amaurosis_fu

gax?sids=2&q=Amaurosis+fugax&qpvt=Amaurosis+fu

gax

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 . 2003;289(12):1523-1532 (doi:10.1001/jama.289.12.1523) JAMA

 Denis Nash; Laurence Magder; Mark Lustberg; et al.  

Perimenopausal and Postmenopausal WomenBlood Lead, Blood Pressure, and Hypertension in

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Blood Lead Levels and Hypertension

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ORIGINAL CONTRIBUTION

Blood Lead, Blood Pressure, andHypertension in Perimenopausaland Postmenopausal WomenDenis Nash, PhD, MPHLaurence Magder, PhD, MPHMark Lustberg, PhDRoger W. Sherwin, MDRobert J. Rubin, PhDRachel B. Kaufmann, PhDEllen K. Silbergeld, PhD

SINCE THE 1970S, CONSIDERABLE

attention has been paid to thepossibility that low levels of leadexposure among adults in the

general population can elevate bloodpressure and increase the risk for hy-pertension, a leading risk factor for car-diovascular disease morbidity and mor-tality.1-3 Evidence for this associationfrom the epidemiological literature iscompelling,4 but the exact causal na-ture of the relationship remains con-troversial.

The notion that lead exposure may in-fluence blood pressure in humans is bio-logically plausible. Lead induces hyper-tension in rats,5,6 and other animal datasuggest that lead acts at multiple siteswithin the cardiovascular system, in-cluding direct effects on the excitabilityand contractility of the heart, alterationof the compliance of the vascular smoothmuscle tissue, and direct action on partsof the central nervous system respon-sible for blood pressure regulation.2 Evi-dence in animals also suggests that leadmay affect blood pressure through the re-nin-angiotensin system.6 Lead is neph-rotoxic to humans, and alteration of

Author Affiliations: Department of Epidemiology andPreventive Medicine, University of Maryland Schoolof Medicine, Baltimore (Drs Nash, Magder, Lust-berg, Sherwin, and Silbergeld); New York City De-partment of Health and Mental Hygiene, HIV/AIDSSurveillance and Epidemiology Program, New York (DrNash); Department of Epidemiology, Tulane Univer-sity School of Public Health and Tropical Medicine, NewOrleans, La (Dr Sherwin); Department of Environ-mental Health Sciences, The Johns Hopkins Univer-sity Bloomberg School of Public Health, Baltimore, Md

(Dr Rubin); and National Center for EnvironmentalHealth, Centers for Disease Control and Prevention,Atlanta, Ga (Dr Kaufmann). Dr Silbergeld is now withthe Department of Environmental Health Sciences, TheJohns Hopkins University Bloomberg School of Pub-lic Health, Baltimore, Md.Corresponding Author and Reprints: Denis Nash, PhD,MPH, New York City Department of Health and Men-tal Hygiene, HIV/AIDS Surveillance and Epidemiol-ogy Program, 346 Broadway, Room 706, New York,NY 10013 (e-mail: dnash@health.nyc.gov).

Context Lead exposures have been shown to be associated with increased bloodpressure and risk of hypertension in older men. In perimenopausal women, skeletallead stores are an important source of endogenous lead exposure due to increasedbone demineralization.

Objective To examine the relationship of blood lead level with blood pressure andhypertension prevalence in a population-based sample of perimenopausal and post-menopausal women in the United States.

Design, Setting, and Participants Cross-sectional sample of 2165 women aged 40to 59 years, who participated in a household interview and physical examination, fromthe Third National Health and Nutrition Examination Survey conducted from 1988 to 1994.

Main Outcome Measures Associations of blood lead with blood pressure and hy-pertension, with age, race and ethnicity, cigarette smoking status, body mass index,alcohol use, and kidney function as covariates.

Results A change in blood lead levels from the lowest (quartile 1: range, 0.5-1.6µg/dL) to the highest (quartile 4: range, 4.0-31.1 µg/dL) was associated with smallstatistically significant adjusted changes in systolic and diastolic blood pressures. Womenin quartile 4 had increased risks of diastolic (�90 mm Hg) hypertension (adjusted oddsratio [OR], 3.4; 95% confidence interval [CI], 1.3-8.7), as well as moderately in-creased risks for general hypertension (adjusted OR, 1.4; 95% CI, 0.92-2.0) and sys-tolic (�140 mm Hg) hypertension (adjusted OR, 1.5; 95% CI, 0.72-3.2). This asso-ciation was strongest in postmenopausal women, in whom adjusted ORs for diastolichypertension increased with increasing quartile of blood lead level compared with quar-tile 1 (adjusted OR, 4.6; 95% CI, 1.1-19.2 for quartile 2; adjusted OR, 5.9; 95% CI,1.5-23.1 for quartile 3; adjusted OR, 8.1; 95% CI, 2.6-24.7 for quartile 4).

Conclusions At levels well below the current US occupational exposure limit guide-lines (40 µg/dL), blood lead level is positively associated with both systolic and dias-tolic blood pressure and risks of both systolic and diastolic hypertension among womenaged 40 to 59 years. The relationship between blood lead level and systolic and dias-tolic hypertension is most pronounced in postmenopausal women. These results pro-vide support for continued efforts to reduce lead levels in the general population, es-pecially women.JAMA. 2003;289:1523-1532 www.jama.com

©2003 American Medical Association. All rights reserved. (Reprinted) JAMA, March 26, 2003—Vol 289, No. 12 1523

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kidney function may precede the devel-opment of hypertension.7,8 However,whether lead affects blood pressurethrough altering kidney function in hu-mans is not known.

A case-control investigation of menfrom the Normative Aging Study9 re-ported significantly higher levels of leadin skeletal and blood compartmentsamong men with hypertension com-pared with normotensives. The all-male study population had mean base-line blood lead levels of 6.3 µg/dL,similar to men in the general popula-tion.10 An increase from the midpointof the lowest quintile to the highestquintile of bone lead was associatedwith an adjusted odds ratio (OR) of1.5 (95% confidence interval [CI],1.1-1.8) for hypertension, suggestingthat cumulative lead exposure, repre-sented by bone lead stores, may be anindependent risk factor for hyperten-sion in the general population.9

Evidence suggests that bone leadstores contribute to circulating levelsof lead in blood.11-13 In particular, bloodlead levels in women appear to increaseduring the menopausal transition,because of the mobilization of skeletallead stores associated with bone demin-eralization.14-18 The impactof these smallbut significant increases in blood leadin postmenopausal compared with pre-menopausal women is difficult to inter-pret, because relatively few studies haveexamined the health impacts of lead inwomen. A case-control study7 of 297women with hypertension who partici-pated in the Nurses’ Health Studyshowed that increases in bone patellalead levels from the 10th to the 90th per-centile were associated with increasedrisks of hypertension (OR, 1.86, 95%CI, 1.09-3.19). However, informationabout menopausal status was extremelylimited in this study.7

The objective of our investigation wasto examine the relationship of blood leadlevels with blood pressure and hyper-tension in a population-based sample ofperimenopausal and postmenopausalwomen in the United States. We se-lected blood pressure and hyperten-sion as outcomes because of the epide-

miological data associating relatively lowlevels of lead in the blood with cardio-vascular outcomes1,2,4,19-38 and becausehypertension is a significant health con-cern for women after menopause.39

METHODSThe study population included womenfrom the Third National Health and Nu-trition Examination Survey (NHANESIII), a cross-sectional sample obtainedthrough a complex survey design, rep-resenting the US civilian, noninstitu-tionalized population. During a 6-yearperiod (1988-1994), participants tookpart in a household interview and anin-depth physical examination withlaboratory tests. Full details of the sur-vey design have been published by theNational Center for Health Statistics ofthe Centers for Disease Control andPrevention.40

Our investigation focused on the sub-set of 2574 women aged 40 to 59 yearswho participated in the NHANES IIIsurvey interview. From this group, 409women were excluded for the follow-ing reasons: 211 did not undergo aphysical examination or blood test-ing; 77 did not have information aboutblood lead levels; and 121 women ofethnicity other than non-Hispanicblack, non-Hispanic white, and Mexi-can American were excluded becauseof small numbers in any single self-reported category. The remaining 2165women constituted the sample used.

DefinitionsBlood Pressure and Hypertension. Weused the mean of 3 systolic and dias-tolic blood pressure measurements, allof which were taken by a physician atthe end of the 4-hour physical exami-nation that occurred in the NHANESmobile examination center. Womenwere categorized as hypertensive if anyof the following criteria were met: cur-rent user of blood pressure medica-tion (self-report), a systolic blood pres-sure of 140 mm Hg or higher, or adiastolic blood pressure of 90 mm Hgor higher. We also examined separatedichotomous variables for systolic hy-pertension and diastolic hypertension

using these cutoff values, excluding per-sons who reported being treated for hy-pertension. More details on measure-ment of and outcomes related to bloodpressure and hypertension in NHANESIII have been published elsewhere.3

Blood Lead. Blood samples were ob-tained by venipuncture during thephysical examination. Blood lead con-centration was measured by graphitefurnace atomic absorption spectropho-tometry at the laboratories of the Na-tional Center for Environmental Healthat the Centers for Disease Control andPrevention in Atlanta, Georgia. The as-say detection limit was 1.0 µg/dL. Eachsample analysis was performed in du-plicate, and the mean of both measure-ments was used in these analyses. Allblood lead levels less than 1.0 µg/dLwere assigned a value of 0.5 µg/dL tobe consistent with previous analyses ofNHANES III lead data by other inves-tigators.10

Menopausal Status. Women were cat-egorized as premenopausal (ovarianfunction intact), surgically menopausal(both ovaries removed surgically be-fore cessation of menses), and naturallymenopausal (nonsurgical cessation ofovarian function). Women without his-tories of reproductive surgery were clas-sified as premenopausal if they re-ported a menstrual period during theprevious 12 months and postmeno-pausal if they did not. Women report-ing having undergone hysterectomy(without ovariectomy) within a monthof the last menstrual period were as-signed a menopausal classification basedon their age (�51 years, premeno-pausal; �51 years, naturally meno-pausal). Women who underwent bilat-eral ovariectomy within 1 month of thedate of the last menstrual period wereclassified as surgically menopausal.Women who underwent hysterectomyor ovariectomy more than 1 month af-ter the reported date of the last men-strual period were classified as natu-rally menopausal. A total of 101 womencould not be assigned a menopausal sta-tus due to missing information.

Kidney Function. Serum creatininewas measured because it is the most

BLOOD LEAD, BLOOD PRESSURE, AND HYPERTENSION IN WOMEN

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specific of the 3 measures of kidneyfunction available in NHANES III (se-rum creatinine, urinary creatinine clear-ance, and blood urea nitrogen) and wasconsistent with other recent studies ofthe effects of lead on the kidney.41

Covariates. Information about raceand ethnicity (non-Hispanic black,non-Hispanic white, and MexicanAmerican), age (years), cigarette smok-ing history (current, former, or never),family income, and education was ob-tained from the household interview.Information about body mass index(BMI, calculated as weight in kilo-grams divided by the square of heightin meters) and alcohol use (amountconsumed per week) was obtained fromthe physical examination and exami-nation-associated questionnaire, re-spectively. A 4-level categorical vari-able for weekly alcohol intake wascreated with the following levels: none,less than 1, 1 to 2, or 3 or more drinksper week. The poverty income ratio, aratio of family income to the povertylevel income for a given family size ad-justed to the poverty threshold for theyear of the interview, was used to cre-ate a 3-level family income variable. Aparticipant was assigned a family in-come higher than the poverty level ifthe poverty income ratio was more than1, at or lower than poverty if the pov-erty income ratio was less than or equalto 1, and missing if the survey partici-pant did not report a family incomelevel. A 4-level education variable wascreated on the basis of the number ofyears of education reported by the sur-vey participant (0-11 years=�highschool; 12 years = completed highschool; 12-15 years=some college; and�16 years=completion of college orhigher).

Statistical MethodsWe used multiple linear regression mod-els to examine the associations of bloodlead and menopausal status with sys-tolic and diastolic blood pressures.Analyses that examined systolic and di-astolic blood pressure as continuous out-come variables excluded the 368 womenwith hypertension who were treated. We

used multiple logistic regression to ex-amine the risks of hypertension (gen-eral, systolic, and diastolic) by catego-rizing blood lead in terms of quartilesand comparing those women in bloodlead quartiles 2, 3, and 4 with those inquartile 1; these analyses were strati-fied by menopausal status.

Models were constructed based onoutcomes known to be biologically as-sociated with blood pressure (age, raceand ethnicity, BMI, and serumcreatinine), including the study vari-able blood lead. Potential confound-ing variables (education, poverty in-come ratio, alcohol use, and cigarettesmoking status) were included if theywere found to be significantly associ-ated with blood pressure outcomes inany 1 of the models before the inclu-sion of blood lead. Final regression co-variates included age, race and ethnic-ity, alcohol use, cigarette smokingstatus, BMI, and kidney function.

Statistical analyses were conducted us-ing SAS version 6 (SAS Institute, Cary,NC), incorporating the examinationsampling weights of NHANES III.40 Thestatistical software package SUDAANversion 7.0 (Research Triange Insti-tute, Research Triangle Park, NC) wasused to calculate SEs for the estimates,accounting for both the weights and thecomplex survey design. Linear regres-sion coefficients reported are unstand-ardized. The significance of regressioncoefficients was evaluated using theWald �2 test. Statistical tests for trendsof categorical variables were carried outin regression models by coding levels asintegers (scores) and evaluating tests forsignificance on the slope of the regres-sion line. Statistical tests with P�.05were considered statistically signifi-cant. All estimates of proportions, re-gression coefficients, and ORs areweighted to the 1990 US Census popu-lation.

RESULTSOverall, the mean blood lead level forwomen aged 40 to 59 years was 2.9 µg/dL, and the means for the quartiles ofblood lead ranged from 1.0 µg/dL to 6.3µg/dL in the lowest and highest quar-

tile, respectively (TABLE 1). Women inthe higher quartiles of blood lead tendedto be older, current smokers, regulardrinkers, poorer, less educated, andmore likely to be non-Hispanic blackthan those in the lower quartiles. All ofthese variables were significantly asso-ciated with blood lead level.

Of the 2165 women in the sample,604 were classified as hypertensivebased on their systolic and diastolicblood pressures (n=231, untreated), aswell as whether they self-reported cur-rently taking antihypertensive medica-tions (n=373). Of those that were un-treated (n = 231), 123 had systolichypertension only, 30 had diastolic hy-pertension only, and 78 had both sys-tolic and diastolic hypertension. Ofthose who were treated for hyperten-sion (n=373), 202 had neither sys-tolic nor diastolic hypertension, 102 hadsystolic hypertension only, 14 had di-astolic hypertension only, 50 had bothsystolic and diastolic hypertension, and5 did not have a systolic or diastolicblood pressure measurement during theexamination.

In these crude analyses, blood leadquartile was significantly associatedwith systolic blood pressure (P=.03)but not diastolic blood pressure(P=.86) (TABLE 2). A significant dose-response existed between blood leadquartile andgeneralhypertensionpreva-lence,with19.4%ofwomenhavinggen-eral hypertension in the lowest quar-tile compared with 28.3% in the highestquartile. However, although dose-response trends appeared to exist, bloodlead quartile was not significantly asso-ciated specifically with systolic or dias-tolic hypertension prevalence (P=.09and P=.25, respectively).

Systolic and DiastolicBlood PressureIn multivariate analyses, blood lead wassignificantly associated with both sys-tolic and diastolic blood pressures(TABLE 3). In these regression mod-els, a difference in blood lead levels be-tween the lowest and highest quartileswas associated with a difference of 1.7mm Hg in systolic blood pressure and

BLOOD LEAD, BLOOD PRESSURE, AND HYPERTENSION IN WOMEN

©2003 American Medical Association. All rights reserved. (Reprinted) JAMA, March 26, 2003—Vol 289, No. 12 1525

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1.4 mm Hg in diastolic blood pres-sure, after adjustment for age, race andethnicity, cigarette smoking, BMI, al-cohol use, and kidney function. Omis-sion of the serum creatinine variable inthe multivariable models for blood leadand blood pressure (both systolic and

diastolic) did not alter the signifi-cance of the blood lead variable.

General HypertensionBefore incorporating blood lead level inthe multiple logistic regression model(TABLE 4), the most important factors

independently increasing the ORs ofgeneral hypertension in women in-cluded increasing age, being non-Hispanic black, having an alcohol in-take of less than 1 drink per week, andincreasing BMI. Adding blood lead levelto the model did not greatly alter any of

Table 1. Weighted Descriptive Characteristics of Adult Women Aged 40 to 59 Years Participating in the Third National Health and NutritionExamination Survey*

CharacteristicTotal

(N = 2165)

Blood Lead Quartile

PValue

Quartile 1(n = 568)

Quartile 2(n = 498)

Quartile 3(n = 556)

Quartile 4(n = 543)

Blood lead level, mean (range), µg/dL 2.9 (0.50-31.1) 1.0 (0.5-1.6) 2.1 (1.7-2.5) 3.2 (2.6-3.9) 6.4 (4.0-31.1)

Race and ethnicity, %Non-Hispanic white 83.9 87.4 86.5 83.4 76.3

Non-Hispanic black 11.7 8.1 9.3 12.6 18.5 �.001

Mexican American 4.4 4.5 4.2 4.1 5.2

Age, mean (SE), y 48.2 (0.2) 46 (0.32) 48 (0.44) 49 (0.34) 50.4 (0.39) �.001

Body mass index, mean (SE) 27.6 (0.25) 28.4 (0.58) 27.5 (0.31) 27.6 (0.34) 26.9 (0.29) .04

Cigarette smoking history, %Current 25.0 8.1 20.2 35.2 42.8

Former 25.5 30.4 25.2 19.2 26.5 �.001

Never 49.5 61.5 54.6 45.6 30.7

Alcohol use, %None 56.8 62.6 60.1 54.0 47.8

�1 per week 15.2 14.5 15.9 15.6 14.6�.001

1-2 per week 17.1 14.5 14.4 21.4 18.6

�3 per week 11.0 8.5 9.5 9.0 19.0

Household income, %At or below poverty 8.8 6.1 7.7 8.0 15.1

Above poverty 84.9 90.3 84.4 84.8 78.0 �.001

Missing 6.3 3.6 8.0 7.2 6.9

Education, %�High school 18.9 13.0 16.7 22.6 25.6

Completed high school 40.0 40.0 43.1 38.2 38.5�.001

Some college 19.9 18.4 21.9 21.0 18.5

College or higher 21.1 28.6 18.3 18.2 17.5

*Body mass index is calculated as weight in kilograms divided by the square of height in meters. P values obtained from �2 test (categorical variables) or analysis of variance(continuous variables) based on an overall test across quartiles.

Table 2. Weighted Distributions of Blood Pressure–Related Variables Among Adult Women Aged 40 to 59 Years Participating in the ThirdNational Health and Nutrition Examination Survey

CharacteristicTotal

(N = 2165)

Blood Lead Quartile

PValue*

P forTrend

Quartile 1(n = 568)

Quartile 2(n = 498)

Quartile 3(n = 556)

Quartile 4(n = 543)

Blood lead level, mean (range), µg/dL 2.9 (0.50-31.1) 1.0 (0.5-1.6) 2.1 (1.7-2.5) 3.2 (2.6-3.9) 6.4 (4.0-31.1)

Blood pressure, mean (SE), mm HgSystolic 118.7 (0.48) 117.2 (0.95) 117.7 (0.83) 119.3 (1.10) 121.2 (0.92) .03 �.001

Diastolic 74.1 (0.29) 73.7 (0.51) 74.2 (0.53) 74.2 (0.62) 74.3 (0.62) .86 .79

Hypertension, %General† 23.0 19.4 20.6 25.5 28.3 .05 �.001

Systolic �140 mm Hg‡ 8.4 6.2 6.6 10.4 11.4 .09 �.001

Diastolic �90 mm Hg‡ 4.7 3.1 4.1 5.1 7.1 .25 �.001

*P values obtained from �2 test (categorical variables) or analysis of variance (continuous variables) based on an overall test across quartiles.†General hypertension defined as systolic blood pressure of 140 mm Hg or higher, diastolic blood pressure of 90 mm Hg or higher, or self-report of prescription antihypertensive

treatment.‡Excludes women who reported being currently treated for hypertension.

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the existing associations between age,race and ethnicity, alcohol intake, andBMI. For women in the highest 2 quar-tiles of blood lead level relative to thelowest quartile, the adjusted ORs of hy-pertension were elevated but not sig-nificantly (OR, 1.3; 95% CI, 0.90-2.0 andOR, 1.4; 95% CI, 0.90-2.0, for quartiles3 and 4, respectively). Separate modelsof these associations for premeno-pausal women and postmenopausalwomen yielded similar results, with theexception that serum creatinine was

strongly associated with general hyper-tension in premenopausal women.

Systolic and Diastolic HypertensionAfter similar adjustment, a weak asso-ciation existed for untreated systolic hy-pertension. For women in the fourthquartile of blood lead, the ORs were thehighest (OR, 1.55; 95% CI, 0.72-3.20)(TABLE 5). The adjusted ORs of dias-tolic hypertension relative to women inthe lowest quartile of blood lead level in-creased with a clear dose-response (quar-

tile 2: OR, 1.5; 95% CI, 0.61-3.7; quar-tile 3: OR, 2.1; 95% CI, 0.76-5.9; andquartile 4: OR, 3.4; 95% CI, 1.3-8.7).

Stratification by menopausal status re-vealed a weak dose-response relation-ship between blood lead level and sys-tolic hypertension in premenopausalwomen, and a significantly elevated ORof systolic hypertension in postmeno-pausal women in the second and thirdquartiles of blood lead relative to womenin the lowest quartile (quartile 2: OR, 3.0;95% CI, 1.3-6.9 and quartile 3: OR, 2.7;

Table 3. Unstandardized Regression Coefficients for Blood Lead and Systolic Blood Pressure and Diastolic Blood Pressure in Women Aged 40to 59 Years Not Treated for Hypertension*

All Women(N = 1786) P Value

PremenopausalWomen

(n = 1084) P Value

PostmenopausalWomen(n = 633) P Value

Systolic Blood Pressure, Regression Coefficients (SE)

R 2 0.22 0.22 0.19

Intercept 61.1 (3.88) 57.4 (6.62) 56.1 (7.22)

Blood lead, µg/dL 0.32 (0.16) .03 0.14 (0.26) .59 0.42 (0.21) .29

Age, y 0.70 (0.08) �.001 0.77 (0.15) �.001 .86 (0.14) .26

Race and ethnicityNon-Hispanic black −4.01 (1.07) −4.82 (1.4) −3.89 (2.04)Mexican American −1.25 (0.97) �.001 −1.54 (1.31) .002 −1.01 (1.61) .32Non-Hispanic white 1.0 1.0 1.0

Alcohol use�3 per week −2.10 (1.55) −1.78 (2.12) −2.31 (3.26)1-2 per week −1.11 (1.39) .32 0.60 (1.37) .77 −5.33 (2.78) .30�1 per week 0.18 (1.12) 0.14 (1.29) 0.86 (2.33)None 1.0 1.0 1.0

Cigarette smoking statusCurrent 1.24 (1.09) 0.77 (1.27) 0.72 (1.81)Former 0.80 (1.43) .32 0.22 (1.89) .83 1.03 (1.43) .20Never 1.0 1.0 1.0

Body mass index 0.81 (0.08) �.001 0.82 (0.10) �.001 0.79 (0.17) �.001

Serum creatinine 1.10 (1.53) .002 2.64 (0.96) .006 −2.96 (2.50) .01

Diastolic Blood Pressure, Regression Coefficients (SE)

R 2 0.14 0.17 0.12

Intercept 56.8 (2.49) 52.2 (4.52) 61.5 (3.91)

Blood lead, µg/dL 0.25 (0.09) .009 0.38 (0.25) .12 0.14 (0.13) .04

Age, y 0.07 (0.05) .13 0.13 (0.11) .25 0.07 (0.06) �.001

Race and ethnicityNon-Hispanic black −1.51 (0.50) −1.93 (0.71) −1.18 (0.89)Mexican American 0.65 (0.58) .001 0.92 (0.79) .002 0.47 (1.10) .16Non-Hispanic white 1.0 1.0 1.0

Alcohol use�3 per week −2.04 (0.94) −2.31 (1.62) −1.39 (1.33)1-2 per week −0.73 (0.77)

.18−0 (0.82)

.54−2.57 (1.43)

.07�1 per week −0.14 (0.73) 0.09 (0.97) −0.30 (1.18)None 1.0 1.0 1.0

Cigarette smoking statusCurrent 2.83 (0.70) 3.25 (0.94) 2.18 (1.21)Former 1.16 (0.90) �.001 1.39 (1.21) .002 0.09 (0.78) .76Never 1.0 1.0 1.0

Body mass index 0.47 (0.05) �.001 0.51 (0.05) �.001 0.39 (0.10) �.001

Serum creatinine 1.11 (1.02) .28 2.26 (0.58) �.001 −2.15 (0.87) .24

*Body mass index is calculated as weight in kilograms divided by the square of height in meters. A total of 69 women could not be assigned a menopausal status due to missingdata.

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95% CI, 1.2-6.2). A dose-response re-lationship was apparent for blood leadquartile and diastolic hypertension,which was particularly striking for post-menopausal women.

COMMENTTo our knowledge, this is the first studyto examine the effects of blood lead andblood pressure in perimenopausalwomen. After accounting for age, raceand ethnicity, alcohol intake, ciga-rette smoking status, BMI, and kidneyfunction, we found a significant asso-ciation between blood lead and sys-tolic and diastolic hypertension preva-lence among women aged 40 to 59 yearsin the US population. We selected thispopulation to analyze the role of meno-pausal status, which we and others haveshown can influence blood lead levelsin women.14-17,42,43 Furthermore, this isthe age range at which the risks for hy-

pertension increase markedly in wom-en.39,44 The highest quartile of blood lead(mean, 6.3 µg/dL) was associated witha 3.4-fold increase in the risks of dias-tolic hypertension (95% CI, 1.3-8.7)relative to those in the lowest blood leadquartile (mean, 1.0 µg/dL). These riskswere considerably higher for postmeno-pausal women. In addition, blood leadwas a significant, positive predictor ofboth elevated systolic and diastolicblood pressure in these women. A dif-ference in blood lead levels between thelowest quartile and the highest quar-tile was associated with a difference of1.7 mm Hg in systolic blood pressureand 1.4 mm Hg in diastolic blood pres-sure. Blood lead is among the few pre-dictors of both systolic and diastolicblood pressures in perimenopausal USwomen. Per unit change, blood lead wasa stronger predictor of diastolic bloodpressure than age.

The results are consistent with thoseof Korrick et al,7 who found an asso-ciation between self-reported hyper-tension and bone lead in older women.In a study of 45-year-old women liv-ing in Copenhagen County, Den-mark, higher blood lead levels were as-sociated with elevated diastolic bloodpressure.29 Neither study accounted formenopausal status in either blood leadlevel or hypertension analyses.

In analyses of systolic and diastolicblood pressures, the relationship be-tween blood lead and blood pressure wasnot stronger for blacks than for whites,nor did blood lead levels explain racialdifferences in hypertension preva-lence. In fact, the blood lead and hyper-tension relationships reported ap-peared to be less pronounced amongblacks compared with the cohort as awhole. However, stratification of the co-hort by race and ethnicity resulted insmall sample sizes in each blood leadquartile, limiting precision.

The associations of blood lead withsystolic and diastolic hypertension weremuch more pronounced for postmeno-pausal women than for premenopausalwomen. The reasons for this associa-tion are unclear. Postmenopausalwomen may be more sensitive to the hy-pertensive effects of lead because of lossof estrogen at menopause.44 Estrogen hasbeen postulated to protect women fromage-related increases in blood pres-sure,44 although results from a largerandomized clinical trial have not sup-ported this hypothesis.45 This observa-tion also may reflect complex relation-ships between bone lead and blood lead,which are altered by the changes in bonemineral metabolism that accompany themenopausal transition.

Whether lead affects blood pressurethrough altering kidney function in hu-mans is not known. Lead is nephro-toxic to humans, and alteration ofkidney function may precede the devel-opment of hypertension.7,8 Kidney func-tion, as measured by serum creatinine,was found to be significantly positivelyassociated with both systolic and dias-tolic blood pressures in premeno-pausal women who are untreated for

Table 4. Adjusted Odds Ratio of General Hypertension, Stratified by Menopausal Status*

Odds Ratio (95% Confidence Interval)

All Women(N = 2165)

Adjusted†

All Women(N = 2165)

PremenopausalWomen

(n = 1214)

PostmenopausalWomen(n = 850)

Blood lead quartile1 1.0 1.0 1.0

2 1.0 (0.63-1.6) 0.78 (0.38-1.6) 0.73 (0.40-1.3)

3 1.3 (0.87-2.0) 1.4 (0.82-2.4) 1.3 (0.75-2.2)

4 1.4 (0.92-2.0) 1.5 (0.78-2.8) 1.3 (0.68-2.3)

Age, y 1.1 (1.1-1.1) 1.1 (1.1-1.1) 1.1 (1.0-1.1) 1.1 (1.0-1.2)

Race and ethnicityNon-Hispanic black 2.3 (1.7-3.1) 2.2 (1.7-2.9) 2.4 (1.5-3.7) 2.2 (1.5-3.2)

Mexican American 0.90 (0.60-1.4) 0.90 (0.60-1.3) 1.1 (0.60-1.7) 0.80 (0.40-1.5)

Non-Hispanic white 1.0 1.0 1.0 1.0

Alcohol use�3 per week 1.0 (0.60-1.7) 1.0 (0.60-1.8) 0.90 (0.40-1.9) 1.0 (0.40-2.7)

1-2 per week 0.90 (0.70-1.3) 1.0 (0.70-1.3) 1.2 (0.80-1.6) 0.70 (0.40-1.4)

�1 per week 1.9 (1.2-3.0) 1.9 (1.2-3.1) 1.9 (0.90-4.0) 1.8 (0.90-3.7)

None 1.0 1.0 1.0 1.0

Cigarette smoking statusFormer 0.80 (0.50-1.4) 0.90 (0.50-1.4) 0.80 (0.40-1.5) 0.90 (0.50-1.6)

Current 1.0 (0.70-1.4) 1.1 (0.80-1.6) 1.5 (0.80-2.9) 0.90 (0.50-1.4)

Never 1.0 1.0 1.0 1.0

Body mass index 1.1 (1.1-1.1) 1.1 (1.1-1.2) 1.1 (1.1-1.1) 1.1 (1.1-1.2)

Serum creatinine 2.5 (0.60-10.1) 2.3 (0.60-9.2) 7.4 (1.7-32.7) 1.1 (0.50-2.4)

*Body mass index is calculated as weight in kilograms divided by the square of height in meters. General hypertensiondefined as systolic blood pressure of 140 mm Hg or higher, diastolic blood pressure of 90 mm Hg or higher, orself-report of prescription antihypertensive treatment. A total of 101 women could not be assigned a menopausalstatus due to missing data. For every unit change in each of these variables (age, body mass index, serum creati-nine), the regression coefficient represents the increase in odds of hypertension for each covariate.

†Adjusted for age, race, alcohol intake, cigarette smoking status, body mass index, and serum creatinine clearance.

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hypertension. Perhaps this reflects thatthe kidney can be a common pathwayfor blood pressure regulation, and theeffect of lead on the kidney is only partof the relationship between kidney func-tion and blood pressure. However, con-trolling for kidney function did not re-duce the association of blood lead withblood pressure and hypertension, aswould be expected if kidney functionwere along the causal pathway. In thepresent investigation, serum creatininewas both a sensitive and significant pre-dictor of general hypertension in pre-menopausal women. For every unit in-crease in serum creatinine, the risks ofhypertension increased more than 7-fold(OR, 7.4; 95% CI, 1.7-32.7). However,

a significant association between leadand general hypertension was not found.

The mechanisms of lead-induced hy-pertension are not well-characterized,even in animal models. One hypoth-esis is that lead induces hypertensionthrough direct effects on the kidney. Arecent retrospective study of 509 healthyparticipants of the Normative AgingStudy found blood lead levels to be sig-nificantly positively correlated with se-rum creatinine levels.41 A study of lead-exposed workers, with high blood leadlevels (mean, 37 µg/dL), reported in-creases in diastolic blood pressure andin levels of urinary biomarkers for re-nal function.7 Batuman et al46 reportedthat patients with essential hyperten-

sion who had reduced renal function hadsignificantly more chelatable lead thanthose with essential hypertension withnormal renal function.

In the present study, kidney func-tion measured by serum creatinine didnot appear to mediate the associationsbetween blood lead and blood pres-sure. Thus, lead may act on blood pres-sure through effects on the vasculatureor central nervous system, or more sen-sitive measures of renal function maybe required to test mechanistic hypoth-eses. However, Staessen47 reported no as-sociation between renal markers of leadtoxicity and blood pressure in a largecohort study of women. The magni-tude of the effects of blood lead on blood

Table 5. Adjusted Odds Ratios for Hypertension, Systolic Hypertension, and Diastolic Hypertension by Blood Lead Quartile*

Blood Lead Quartile

Quartile 1 Quartile 2 Quartile 3 Quartile 4

All Premenopausal and Postmenopausal Women

No. in sample 568 498 556 543

Blood lead, mean (range), µg/dL 1.0 (0.5-1.6) 2.1 (1.7-2.5) 3.2 (2.6-3.9) 6.4 (4.0-31.1)

General hypertension, OR (95% CI)† 1.0 1.0 (0.63-1.6) 1.3 (0.87-2.0) 1.4 (0.92-2.0)

Premenopausal and Postmenopausal Women Untreated for Hypertension

No. in sample 433 476 438 445

Blood lead, mean (range), µg/dL 0.94 (0.5-1.5) 2.0 (1.6-2.5) 3.1 (2.6-3.8) 6.2 (3.9-31.1)

Systolic hypertension �140 mm Hg, OR (95% CI)‡ 1.0 0.89 (0.41-1.9) 1.4 (0.75-2.7) 1.55 (0.72-3.20)

Diastolic hypertension �90 mm Hg, OR (95% CI)‡ 1.0 1.5 (0.61-3.7) 2.1 (0.76-5.9) 3.4 (1.3-8.7)

All Premenopausal Women

No. in sample 304 302 300 308

Blood lead, mean (range), µg/dL 0.8 (0.5-1.4) 1.8 (1.5-2.1) 2.7 (2.2-3.3) 5.4 (3.4-28.7)

General hypertension, OR (95% CI)† 1.0 0.78 (0.38-1.6) 1.4 (0.82-2.4) 1.5 (0.78-2.8)

Premenopausal Women Untreated for Hypertension

No. in sample 279 277 262 266

Blood lead, mean (range), µg/dL 0.8 (0.5-1.4) 1.8 (1.5-2.1) 2.7 (2.2-3.3) 5.4 (3.4-28.7)

Systolic hypertension �140 mm Hg, OR (95% CI)‡ 1.0 0.88 (0.29-2.7) 1.4 (0.49-3.7) 1.6 (0.62-4.2)

Diastolic hypertension �90 mm Hg, OR (95% CI)‡ 1.0 1.1 (0.31-3.6) 1.8 (0.76-4.2) 3.5 (0.89-13.4)

All Postmenopausal Women

No. in sample 206 227 203 214

Blood lead, mean (range), µg/dL 1.3 (0.5-1.9) 2.5 (2.0-3.1) 3.9 (3.2-4.6) 7.4 (4.7-31.1)

General hypertension, OR (95% CI)† 1.0 0.73 (0.40-1.3) 1.3 (0.75-2.2) 1.3 (0.68-2.3)

Postmenopausal Women Untreated for Hypertension

No. in sample 163 148 166 156

Blood lead, mean (range), µg/dL 1.4 (0.5-2.0) 2.6 (2.1-3.0) 3.8 (3.1-4.6) 7.4 (4.7-31.1)

Systolic hypertension �140 mm Hg, OR (95% CI)‡ 1.0 3.0 (1.3-6.9) 2.7 (1.2-6.2) 2.6 (0.89-7.5)

Diastolic hypertension �90 mm Hg, OR (95% CI)‡ 1.0 4.6 (1.1-19.2) 5.9 (1.5-23.1) 8.1 (2.6-24.7)Abbreviations: OR, odds ratio; CI, confidence interval.*Adjusted for age, race, alcohol intake, cigarette smoking status, body mass index (calculated as weight in kilograms divided by the square of height in meters), and serum cre-

atinine.†General hypertension defined as systolic blood pressure of 140 mm Hg or higher, diastolic blood pressure of 90 mm Hg or higher, or self-report of prescription antihypertensive

treatment.‡Excludes women who reported currently receiving antihypertensive treatment.

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pressure observed in this study are simi-lar to previous investigations, includ-ing 1 study of women.29

Several cross-sectional21-24,29-31,33,48 andprospective29,31,35 population-based stud-ies on the association of lead with sys-tolic and diastolic blood pressures havebeen performed from the mid-1980s.The results of these studies have beenmixed, but there is considerable con-cordance with the directionality of theobserved associations, with most con-sistently finding a weak-positive asso-ciation between blood lead and both sys-tolic and diastolic blood pressure in men,women, blacks, and whites.4 A meta-analysis by Schwartz38 of 15 studies oflead and systolic blood pressure in menestimated that a change in blood leadfrom 5 to 10 µg/dL was associated withan increase of 1.5 mm Hg in systolicblood pressure (95% CI, 0.87-1.63mm Hg), which compares well with thecorresponding estimate from our study(1.6 mm Hg; 95% CI, 0.97-2.20). Theadjusted ORs from multiple logistic re-gression models performed separately forpremenopausal and postmenopausalwomen (Table 5) show a consistent, al-though not always significant, dose-response relationship between bloodlead quartile and risks of hypertension.These subgroup analyses resulted insmaller numbers of women in the mod-els, and this is reflected in the wide CIsin some of the estimates.

The conventional predictors of bloodlead in the current US population havebeen published in a previous NHANESIII analysis by Brody et al.10 Other non-bone density–related exposures that canresult in elevated blood lead levels inthe United States include residential ex-posure to lead paint, residential prox-imity to a lead smeltering facility, oc-cupational exposure (lead smelter,battery manufacturing, welding, orbridge painting), cigarette smoking, andalcohol intake.15 Those variables asso-ciated with lead and also known to beassociated with blood pressure and hy-pertension (ie, potential confound-ers) were adjusted for in the blood leadand blood pressure and hypertensionanalyses of our study.

The human skeleton is a dynamicphysiological compartment of min-eral metabolism. Women lose as muchas 50% of trabecular bone and 30% ofcortical bone during their lifetime, and30% to 50% of this bone loss occurs inthe early postmenopausal years.49-53 Es-trogen deficiency appears to play a sig-nificant role in bone loss.51,54

Observational evidence suggests thatlead may be mobilized from the skel-eton during periods of increased bonedemineralization, such as during preg-nancy and lactation,12,55-57 very old age,58

and menopause.14-16,59 Two cross-sectional studies14,15 of US women thatwere performed using data from the sec-ond NHANES (NHANES II, 1976-1980) and the Hispanic HANES (1982-1984) documented that postmenopausalwomen have significantly higher bloodlead levels than premenopausal women,controlling for age and other factors re-lated to exogenous lead exposure. An-other study59 also identified meno-pausal status as an independentpredictor of blood lead levels in a ran-dom sample of Scandinavian women.

Hu et al60 noted that bone lead maybe a more appropriate marker of leadexposure for chronic disease out-comes such as hypertension. The pres-ent study is a cross-sectional study inthat the exposures and the outcomeswere measured simultaneously. The rel-evant exposures affecting blood pres-sure and hypertension may occurmonths or years before the observedeffect. For example, the average BMIduring the 5 years preceding the bloodpressure measurement may have moreexplanatory power than BMI mea-sured on the same day as the blood pres-sure. Likewise, cumulative lead expo-sure during the preceding decade, bonelead burden, or serum creatinine maybe more predictive of blood pressurethan blood lead level measured on thesame day as blood pressure. Evidencesuggests that bone lead stores can con-tribute to circulating levels of lead inblood.11-13

The findings of our study are incon-sistent with the notion of a latency pe-riod of months to years between the on-

set of perimenopausal bone loss resultingin increased endogenous lead expo-sure, followed by a chronic effect of leadon blood pressure. A study by Cake etal61 suggests that bone lead released intothe blood may be more bioavailable thanlead resulting from environmental ex-posure. Therefore, if blood lead in peri-menopausal women is more driven bybone lead levels, it is possible that bloodlead levels may be a more sensitive pre-dictor of blood pressure outcomes in thispopulation, because it represents liber-ated skeletal lead stores.

Important methodological chal-lenges exist in observational studies oflead exposure and blood pressure andhypertension. First, if an association be-tween lead exposure and blood pres-sure exists, lead is most likely respon-sible for a relatively small effect onblood pressure, and thus, this associa-tion may be difficult to consistently as-certain in different populations. Sec-ond, when examining small effects, theissue of residual confounding, beyondthat which is controlled in the analy-sis, becomes extremely important. Insuch cases, what may be interpreted asa small effect of blood lead on bloodpressure may actually be due to inad-equate control of confounding fac-tors. However, the restricted age rangechosen for this investigation helps tominimize the effect of confounding byage, which is strongly related to bloodlead, blood pressure, and hyperten-sion. Third, because the mechanisms bywhich lead may act on blood pressurein humans are not well understood, in-vestigators may tend to include morecovariates than necessary in their mod-els or use mechanical, stepwise ap-proaches to modeling. The true size ofthe effect may be decreased by over-controlling. This is a particular prob-lem in studies of environmental lead ex-posure, because blood lead levels arehighly correlated with race and ethnic-ity, income, and education,10 which alsomay be risk factors for outcomes suchas hypertension.49

Whether bone or blood is the appro-priate biomarker for lead exposure instudies of chronic disease outcomes is

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uncertain.60 Blood lead is a marker ofrelatively recent exposures to lead.Hypertension in adults that may be asso-ciated with past exposures to lead is con-sistent with a follow-up study of lead-poisoned children in whom the risks forhypertension were significantly higherthan they were in controls matched byage, sex, race and ethnicity, and neigh-borhood.50 Bone lead is a more appro-priate marker for chronic exposure;however, its interpretation depends onan understanding of bone physiologyand events such as pregnancy andmenopause.11 Future studies of bloodpressure and hypertension should con-sider blood lead and bone lead as inde-pendent factors influencing the risk forhypertension.

The R2 values in Table 3 suggest thatthe models explain 22% and 14% of thevariation in systolic and diastolic bloodpressure, respectively. We interpret thisto mean that much of the variation inblood pressure is random or due to un-known or immeasurable factors. Be-cause blood pressure has been so wellstudied, it is unlikely that there are un-discovered factors responsible for theremaining unexplained variation.

Other factors that contribute to thevariation in blood lead levels observedin our study include measured and un-measured aspects of conventional andbone density–related predictors of bloodlead, as well as other variables that werenot measured by NHANES. However,we controlled for all of the known fac-tors associated with blood pressure andhypertention,3 including alcohol in-take. This approach presumably mini-mizes residual confounding of our es-timate of the associations of blood leadwith blood pressure and hypertension.

Vital status data are not yet avail-able on the NHANES III cohort. How-ever, a recent analysis of men andwomen from the NHANES II cohort byLustberg and Silbergeld62 found el-evated blood lead levels to be associ-ated with a dose-related increase indeaths due to hypertension-relatedcoronary heart disease and stroke forboth men and women. Although thetiming of NHANES II resulted in higher

blood lead levels than our data in ourpopulation, the effects observed in ourstudy also suggest that lead acts on thecardiovascular system and much lowerlevels in the blood.

From a public health perspective, themost important and troubling implica-tion of these findings is that lead ap-pears to increase blood pressure inwomen at very small increments above1.0 µg/dL, well below what is consid-ered deleterious in adults. The meanblood lead level in this sample ofwomen was 2.9 µg/dL. These resultsdemonstrate effects of lead at levels lessthan the US occupational blood lead ex-posure limits (40 µg/dL) and even lessthan the current Centers for DiseaseControl and Prevention level of con-cern for preventing lead poisoning inchildren (10 µg/dL). Finally, the find-ings from our study of associations ofblood lead with systolic and diastolichypertension and blood pressure amongwomen in the general population lendsupport for further studies on the healtheffects of bone lead mobilization dur-ing the menopausal transition. Theseresults provide support for continuedefforts to reduce lead levels in the gen-eral population, especially women.

Author Contributions: Study concept and design:Nash, Magder, Lustberg, Sherwin, Rubin, Kaufmann,Silbergeld.Acquisition of data: Nash.Analysis and interpretation of data: Nash, Magder,Lustberg, Rubin, Kaufmann, Silbergeld.Drafting of the manuscript: Nash, Sherwin, Rubin,Kaufmann, Silbergeld.Critical revision of the manuscript for important in-tellectual content: Nash, Magder, Lustberg, Sherwin,Rubin, Kaufmann, Silbergeld.Statistical expertise: Magder.Obtained funding: Nash, Silbergeld.Administrative, technical, or material support:Lustberg, Silbergeld.Study supervision: Nash, Sherwin, Rubin, Kaufmann,Silbergeld.Funding/Support: This study was supported with anaward from the Centers for Disease Control and Pre-vention/Association of Teacher’s of Preventive Medi-cine cooperative agreement TS 288-14/14 and by agrant from the Heinz Family Foundation.

REFERENCES

1. Pirkle JL, Schwartz J, Landis JR, Harlan WR. Therelationship between blood lead levels and blood pres-sure and its cardiovascular risk implications. Am J Epi-demiol. 1985;121:246-258.2. Kopp SJ, Barron JT, Tow JP. Cardiovascular ac-tions of lead and relationship to hypertension: a re-view. Environ Health Perspect. 1988;78:91-99.3. Burt VL, Whelton P, Roccella EJ, et al. Prevalence of

hypertension in the US adult population: results fromthe Third National Health and Nutrition Examination Sur-vey, 1988-1991. Hypertension. 1995;25:305-313.4. Hertz-Picciotto I, Croft J. Review of the relation be-tween blood lead and blood pressure. Epidemiol Rev.1993;15:352-373.5. Nowack R, Wiecek A, Exner B, Gretz N, Ritz E.Chronic lead exposure in rats: effects on blood pres-sure. Eur J Clin Invest. 1993;23:433-443.6. Vander AJ. Chronic effects of lead on the renin-angiotensin system. Environ Health Perspect. 1988;78:77-83.7. Korrick SA, Hunter DJ, Rotnitzky A, Hu H, SpeizerFE. Lead and hypertension in a sample of middle-aged women. Am J Public Health. 1999;89:330-335.8. Cowley AW Jr, Roman RJ. The role of the kidneyin hypertension. JAMA. 1996;275:1581-1589.9. Hu H, Aro A, Payton M, et al. The relationship ofbone and blood lead to hypertension: the NormativeAging Study. JAMA. 1996;275:1171-1176.10. Brody DJ, Pirkle JL, Kramer RA, et al. Blood leadlevels in the US population: phase 1 of the Third Na-tional Health and Nutrition Examination Survey(NHANES III, 1988 to 1991). JAMA. 1994;272:277-283.11. Gulson BL, Mahaffey KR, Mizon KJ, et al. Con-tribution of tissue lead to blood lead in adult femalesubjects based on stable lead isotope methods. J LabClin Med. 1995;125:703-712.12. Gulson BL, Jameson CW, Mahaffey KR, et al. Preg-nancy increases mobilization of lead from maternal skel-eton. J Lab Clin Med. 1997;130:51-62.13. Smith DR, Osterloh JD, Flegal AR. Use of endog-enous, stable lead isotopes to determine release of leadfrom the skeleton. Environ Health Perspect. 1996;104:60-66.14. Silbergeld EK, Schwartz J, Mahaffey K. Lead andosteoporosis: mobilization of lead from bone in post-menopausal women. Environ Res. 1988;47:79-94.15. Symanski E, Hertz PI. Blood lead levels in rela-tion to menopause, smoking, and pregnancy history.Am J Epidemiol. 1995;141:1047-1058.16. Muldoon SB, Cauley JA, Allen L. Effect of bonemineral density changes on blood lead levels in peri-menopausal women. Paper presented at: Society forEpidemiologic Research; June 1997; Calgary, Al-berta.17. Nash D, Silbergeld E, Magder L, Stolley P. Meno-pause, hormone replacement therapy (HRT), and bloodlead levels among adult women from NHANES III,1988-1994 [abstract]. Am J Epidemiol. 1998;147:S93.18. Silbergeld E, Nash D. Lead and human health: isthis mine exhausted. Progress in Environmental Sci-ence. 2000;1:53-68.19. Pirkle JL, Brody DJ, Gunter EW, et al. The declinein blood lead levels in the United States: the NationalHealth and Nutrition Examination Surveys (NHANES).JAMA. 1994;272:284-291.20. Harlan WR. The relationship of blood lead levelsto blood pressure in the US population. Environ HealthPerspect. 1988;78:9-13.21. Harlan WR, Landis JR, Schmouder RL, et al. Bloodlead and blood pressure: relationship in the adoles-cent and adult US population. JAMA. 1985;253:530-534.22. Pocock SJ, Shaper AG, Ashby D, et al. The rela-tionship between blood lead, blood pressure, stroke,and heart attacks in middle-aged British men. Envi-ron Health Perspect. 1988;78:23-30.23. Neri LC, Hewitt D, Orser B. Blood lead and bloodpressure: analysis of cross-sectional and longitudinaldata from Canada. Environ Health Perspect. 1988;78:123-126.24. Elwood PC, Davey-Smith G, Oldham PD, ToothillC. Two Welsh surveys of blood lead and blood pres-sure. Environ Health Perspect. 1988;78:119-121.

BLOOD LEAD, BLOOD PRESSURE, AND HYPERTENSION IN WOMEN

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25. Elwood PC, Yarnell JW, Oldham PD, et al. Bloodpressure and blood lead in surveys in Wales. Am J Epi-demiol. 1988;127:942-945.26. Sharp DS, Becker CE, Smith AH. Chronic low-level lead exposure: its role in the pathogenesis of hy-pertension. Med Toxicol. 1987;2:210-232.27. Sharp DS, Osterloh J, Becker CE, et al. Blood pres-sure and blood lead concentration in bus drivers.Environ Health Perspect. 1988;78:131-137.28. Sharp DS, Osterloh J, Becker CE, et al. Elevatedblood pressure in treated hypertensives with low-level lead accumulation. Arch Environ Health. 1989;44:18-22.29. Moller L, Kristensen TS. Blood lead as a cardio-vascular risk factor. Am J Epidemiol. 1992;136:1091-1100.30. Proctor SP, Rotnitzky A, Sparrow D, et al. The re-lationship of blood lead and dietary calcium to bloodpressure in the normative aging study. Int J Epide-miol. 1996;25:528-536.31. Staessen JA, Roels H, Fagard R. Lead exposureand conventional and ambulatory blood pressure: aprospective population study. JAMA. 1996;275:1563-1570.32. Staessen J, Sartor F, Roels H, et al. The associa-tion between blood pressure, calcium and other di-valent cations: a population study. J Hum Hypertens.1991;5:485-494.33. Hense HW, Filipiak B, Keil U. The association ofblood lead and blood pressure in population surveys.Epidemiology. 1993;4:173-179.34. Hense HW, Filipiak B, Keil U. Alcohol con-sumption as a modifier of the relation betweenblood lead and blood pressure. Epidemiology. 1994;5:120-123.35. Grandjean P, Hollnagel H, Hedegaard L, et al.Blood lead-blood pressure relations: alcohol intake andhemoglobin as confounders. Am J Epidemiol. 1989;129:732-739.36. Schwartz J. The relationship between blood leadand blood pressure in the NHANES II survey. EnvironHealth Perspect. 1988;78:15-22.37. Schwartz J. Lead, blood pressure, and cardiovas-cular disease in men and women. Environ Health Per-spect. 1991;91:71-75.38. Schwartz J. Lead, blood pressure, and cardiovas-

cular disease in men. Arch Environ Health. 1995;50:31-37.39. Reckelhoff JH. Gender differences in the regula-tion of blood pressure. Hypertension. 2001;37:1199-1208.40. Ezzati T, Massey J, Waksburg J, et al. Sample De-sign: Third National Health and Nutrition Examina-tion Survey. Hyattsville, Md: Dept of Health and Hu-man Services, National Center for Health Statistics;1992. Publication PHS 92-1387.41. Kim R, Rotnitsky A, Sparrow D, et al. A longitu-dinal study of low-level lead exposure and impair-ment of renal function: the Normative Aging Study.JAMA. 1996;275:1177-1181.42. Silbergeld E, Watson L. Exposure to lead duringreproduction and menopause. Fundam Appl Toxi-col. 1995;25:167-168.43. Muldoon SB, Cauley JA, Kuller LH, et al. Life-style and sociodemographic factors as determinantsof blood lead levels in elderly women. Am J Epide-miol. 1994;139:599-608.44. Staessen JA, Celis H, Fagard R. The epidemiol-ogy of the association between hypertension andmenopause. J Hum Hypertens. 1998;12:587-592.45. Hu FB, Grodstein F. Postmenopausal hormonetherapy and the risk of cardiovascular disease: the epi-demiologic evidence. Am J Cardiol. 2002;90:26F-29F.46. Batuman V, Landy E, Maesaka JK, Wedeen RP.Contribution of lead to hypertension with renal im-pairment. N Engl J Med. 1983;309:17-21.47. Staessen J. Low-level lead exposure, renal func-tion and blood pressure. Verhandelingen—Koninklijke Academie voor Geneeskunde van Bel-gie. 1995;57:527-574.48. Sharp DS, Benowitz NL, Osterloh JD, et al. Influ-ence of race, tobacco use, and caffeine use on the re-lation between blood pressure and blood lead con-centration. Am J Epidemiol. 1990;131:845-854.49. Lindquist O, Bengtsson C, Hansson T, Roos B. Bonemineral content in relation to age and menopause inmiddle-aged women: a study of bone density in lum-bar vertebrae by dual photon absorptiometry in a popu-lation sample of women. Scand J Clin Lab Invest. 1981;41:215-223.50. Krolner B, Pors NS. Bone mineral content of thelumbar spine in normal and osteoporotic women: cross-

sectional and longitudinal studies. Clin Sci. 1982;62:329-336.51. Heaney RP, Recker RR, Saville PD. Menopausalchanges in bone remodeling. J Lab Clin Med. 1978;92:964-970.52. Lindsay R, Hart DM, Aitken JM, et al. Long-termprevention of postmenopausal osteoporosis by estro-gen: evidence for an increased bone mass after de-layed onset of estrogen treatment. Lancet. 1976;1:1038-1041.53. Riggs BL, Melton Ld. Involutional osteoporosis.N Engl J Med. 1986;314:1676-1686.54. Nordin B. Osteoporosis with particular referenceto the menopause. In: Alvioli L, ed. The OsteoporoticSyndrome: Detection, Prevention, and Treatment. NewYork, NY: Grune & Stratton; 1983.55. Lagerkvist BJ, Soderberg HA, Nordberg GF, et al.Biological monitoring of arsenic, lead and cadmiumin occupationally and environmentally exposed preg-nant women. Scand J Work Environ Health. 1993;1:50-53.56. Knight EM, Spurlock BG, Edwards CH, et al. Bio-chemical profile of African American women duringthree trimesters of pregnancy and at delivery. J Nutr.1994;124:943S-953S.57. West WL, Knight EM, Edwards CH, et al. Mater-nal low level lead and pregnancy outcomes. J Nutr.1994;124:981S-986S.58. Webber CE, Chettle DR, Bowins RJ, et al. Hor-mone replacement therapy may reduce the return ofendogenous lead from bone to the circulation. Envi-ron Health Perspect. 1995;103:1150-1153.59. Grandjean P, Nielsen GD, Jorgensen PJ, HorderM. Reference intervals for trace elements in blood: sig-nificance of risk factors. Scand J Clin Lab Invest. 1992;52:321-337.60. Hu H, Rabinowitz M, Smith D. Bone lead as a bio-logical marker in epidemiologic studies of chronic tox-icity: conceptual paradigms. Environ Health Per-spect. 1998;106:1-8.61. Cake KM, Bowins RJ, Vaillancourt C, et al. Par-tition of circulating lead between serum and red cellsis different for internal and external sources of lead.Am J Ind Med. 1996;29:440-445.62. Lustberg M, Silbergeld E. Blood lead levels andmortality. Arch Intern Med. 2002;162:2443-2449.

BLOOD LEAD, BLOOD PRESSURE, AND HYPERTENSION IN WOMEN

1532 JAMA, March 26, 2003—Vol 289, No. 12 (Reprinted) ©2003 American Medical Association. All rights reserved.

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Hypertension Evaluation Exam

1. Goals 1. Identify end organ damage

2. Identify signs secondary Hypertension

3. Identify reversible exacerbating factors

4. Document progression

2. Vitals 1. BP Examination

2. Pulse

3. Assess for Obesity

1. Weight and Height

2. Ideal body weight or BMI

3. Waist Circumference (assess for Metabolic

Syndrome)

3. Retinal Exam 1. SEE Funduscopic Changes in Hypertension

4. Neck Exam 1. Thyroid exam

2. Carotid Bruits

3. Neck vein exam

5. Chest exam 1. Congestive Heart Failure signs

2. Palpable intercostal pulses

6. Cardiovascular Exam 1. S4 Gallop rhythm (decreased LV compliance)

2. Tachycardia

3. Accentuated S2 Heart Sound

4. Aortic Insufficiency murmur

5. Abnormal EKG or Echocardiogram

6. Prior Angiography results

7. Abdominal Exam 1. Abdominal bruit

2. Abdominal Aortic Aneurysm

3. Enlarged or tender kidneys (CVA pain)

8. Genitourinary Exam

1. Abnormal Sexual Development

2. Enlarged prostate

9. Peripheral Vascular Disease 1. Femoral bruits

2. Symmetrical pulses

3. Lower extremity shin Hair Loss

10. Neurologic 1. Peripheral Neuropathy

11. Skin Exam 1. Stigmata of Cirrhosis

2. Neurofibromata

3. Chloasma

4. Signs of Cushing's Disease

1. Striae

2. Acne Vulgaris

3. Hirsutism

Hypertension Evaluation Labs

1. Labs: General for All Patients 1. Urinalysis

2. Complete Blood Count (Hemoglobin or

Hematocrit minimum)

3. Fasting lipid profile

4. Chemistry Panel (Chem7, SMA7)

1. Fasting Glucose

2. Serum Potassium (Consider primary

Aldosteronism if Hypokalemia - even

borderline low)

3. Renal Function: Serum Creatinine,

BUN

5. Electrocardiogram

2. Labs: Optional Studies (as indicated) 1. Serum Calcium

2. Uric Acid

3. Chest XRay (evaluate for coarctation, heart

size)

4. 24 hour Urine Creatinine

5. 24 Hour Urine Protein

3. Evaluation: Secondary Hypertension 1. INDICATIONS

1. Hypertension Onset under age 30 or

over age 60

2. Hypertension refractory to

aggressive treatment

3. Previously controlled Hypertension

now refractory

4. Accelerated Hypertension or

Malignant Hypertension

5. Signs OR symptoms of secondary

Hypertension

2. LABS 1. AORTIC COARCTATION

1. Exam

2. Chest XRay

2. CUSHING'S DISEASE 1. 24 hour Urine Cortisol or

Salivary cortisol

3. PHEOCHROMOCYTOMA 1. 24h Urine Metanephrine

2. Vanillyamandelic Acid (VMA)

4. RENAL PARENCHYMAL DISEASE

1. Renal Ultrasound

5. RENAL ARTERY STENOSIS 1. MR Angiography

6. PRIMARY ALDOSTERONISM (STRONGLY CONSIDER IF HYPOKALEMIA)

1. Aldosterone to plasma renin

ratio

Antihypertensive Selection

= Hypertension Monotherapy

1. See Also 1. Hypertension

2. Hypertension Criteria

3. Hypertension Evaluation

2. Step 1: Determine when and how to intervene

1. Review Hypertension Risk Stratification

2. Determine Hypertension Reduction Goal

3. Step 2 1. CONSIDER HYPERTENSION

COMBINATION THERAPY 1. For Refractory Hypertensive

Populations

2. MONOTHERAPY 1. STANDARD INITIAL MONOTHERAPY

CHOICES

1. Diuretics (e.g. Hydrochlorothiazide)

1. If Diuretic is not first, it

should be second

2. Excellent adjunct to

other

antihypertensives

3. Better outcomes than

Lisinopril and

Amlodipine

1. Reduced

risk of CVA,

MI, CHF

over other

agents

2. (2002)

JAMA

288:2981

2. Beta Blocker 3. ACE Inhibitor 4. Angiotensin

Receptor Blocker

2. COMPELLING REASON FOR OTHER ANTIHYPERTENSIVE

1. AntiHypertensives for

Specific Comorbid Diseases

2. Antihypertensives for

Specific Populations

3. AGENTS TO AVOID FOR MONOTHERAPY

1. Alpha blockers

2. Hydralazine

3. Minoxidil

4. Calcium Channel Blockers

4. AVOID IF NON-COMPLIANT (REBOUND HYPERTENSION)

1. Beta Blockers

2. Clonidine

4. Step 3 1. Consider Hypertension Combination Therapy

Hypertension Combination Therapy

= Combination Antihypertensive Therapy,

Resistant Hypertension, Refractory Hypertension

1. See Also 1. Hypertension

2. Hypertension Criteria

3. Hypertension Evaluation

4. Antihypertensive Selection

5. Refractory Hypertensive Populations

2. Indications for Combination Antihypertensive Therapy

1. Failed Hypertension Monotherapy

2. Hypertension

3. Protocol 1. Consider reasons for resistant Hypertension

(see below)

2. Review Hypertension Risk Stratification

3. Determine Hypertension Reduction Goal

4. Advance to next step if BP>15/10 above goal

5. Consolidate medications into combination

agents

4. Causes: Resistant Hypertension 1. NONCOMPLIANCE WITH CURRENT

REGIMEN (MOST COMMON) 1. Recent drug holiday

2. Unfilled prescription

2. INACCURATE BLOOD PRESSURE MEASUREMENT (SEE BP EXAMINATION REGARDING PITFALLS)

3. White coat Hypertension (consider Ambulatory Blood Pressure Monitoring)

4. PROGRESSION OF DISEASE

5. TREATMENT PROGRAM NOT OPTIMIZED 1. Example: Thiazide Diuretics are

ineffective at GFR <30 ml/min (use

Loop Diuretics instead)

6. MEDICATIONS OR DRUGS COUNTERACTING ANTIHYPERTENSIVE (e.g. NSAIDS, Sympathomimetics)

7. COMORBID CONDITION (e.g. Sleep Apnea,

morbid Obesity, Alcohol Abuse, anxiety, Chronic

Pain)

8. SECONDARY HYPERTENSION 1. Hyperaldosteronism represents 20% of

refractory cases (consider if

Hypokalemia)

9. Reference 1. O'Rorke (2001) BMJ 322:1230

5. Preparations: Combinations (assist with cost and compliance)

1. Prinizide (Lisinopril 10-20 mg with

Hydrochlorothiazide 12.5-25 mg)

2. Diovan-Hct (Valsartan 80-160 mg with

Hydrochlorothiazide 12.5 mg)

3. Ziac (Bisoprolol with Hydrochlorothiazide

6.25)

4. Lotrel (Benzapril 10-20 mg with Amlodipine

2.5-10 mg)

5. Tarka (Trandolopril 1-2 mg with Verapamil

180-240 mg)

6. Exforge (Valsartan and Amlodipine)

7. Reserpine 1.25-2.5 mg with

Hydrochlorothiazide 25 mg

8. Tenoretic (Atenolol 50-100 mg with

Chlorthalidone 25 mg)

6. Protocol: Combinations that add 4 drugs in 2 pills for $50-60

1. Tenoretic 100/25 with Lotrel 10/20

2. Tenoretic 100/25 with Prinizide 20/12.5

7. Protocol: Step 1 1. SERUM CREATININE <1.8 MG/DL

1. ACE Inhibitor and Thiazide Diuretic

2. SERUM CREATININE >1.8 MG/DL 1. ACE Inhibitor and Loop Diuretic

8. Protocol: Step 2 1. ADD NON-DIHYDROPYRIDINE CALCIUM

CHANNEL BLOCKER

9. Protocol: Step 3 1. HEART RATE >83

1. Add Low dose Beta Blocker

2. Caution regarding Atrioventricular Block

2. HEART RATE <84 1. Add Dihydropyridine Calcium Channel

Blocker

10. Protocol: Step 4 1. Add long acting Alpha adrenergic blocker (at

night)

2. Add Spironolactone 12.5 to 50 mg po qd

3. Consult Nephrology or Cardiology

11. Protocol: Additional Measures 1. Consider Tekturna (Aliskiren), a Direct renin

inhibitor

12. References 1. Woolley (2007) Park Nicollet Primary Care

Conference, Minneapolis, MN

2. Schwartz (2008) Mayo Selected Topics in

Internal Medicine, Lecture

3. Garg (2005) Am J Hypertens 18:619

Hypertension Management for Specific Comorbid Diseases

= AntiHypertensives for Specific Comorbid Diseases

1. See Also 1. Hypertension

2. Hypertension Criteria

3. Hypertension Evaluation

4. Hypertension Management

5. Antihypertensive Selection

6. Hypertension Management for Specific Populations

7. Isolated Systolic Hypertension

2. Diabetes Mellitus (with or without Diabetic Nephropathy)

1. See Hypertension in Diabetes Mellitus

3. Left Ventricular Hypertrophy (Risk of

sudden death)

1. Central active agonists

2. ACE Inhibitors

3. Calcium Channel Blockers

4. Congestive Heart Failure 1. SYSTOLIC DYSFUNCTION

1. ACE Inhibitor

2. Angiotensin Receptor Blocker

3. Diuretic

4. Beta Blocker (use with caution, CIBIS II,

MERIT-HF)

1. High efficacy with Carvedilol

5. Spironolactone (use with caution, RALES

trial)

2. DIASTOLIC DYSYFUNCTION 1. Calcium Channel Blocker

5. Coronary Artery Disease risk or Myocardial Infarction

1. General 1. Beta Blocker

2. ACE Inhibitor (HOPE trial)

2. Angina 1. Beta Blockers

2. Calcium Channel Blockers (Not

Nifedipine)

6. Atrial Tachycardia and Atrial Fibrillation 1. Beta Blockers

2. Nondihydropyridine calcium antagonists

7. Benign Prostatic Hyperplasia 1. Alpha antagonist

2. Avoid Diuretics

8. Dyslipidemia 1. Alpha antagonists

2. Diuretics do not worsen Hyperlipidemia

3. Beta Blockers do not worsen Hyperlipidemia

9. Renal Disease 1. ACE Inhibitor

2. Diuretic

10. Pregnancy 1. Methyldopa

2. Hydralazine

3. Labetolol

4. Do not use ACE Inhibitor = teratogenesis

11. Obesity 1. Diuretics

12. Gout 1. Avoid Thiazide Diuretics

13. Osteoporosis 1. Thiazide Diuretics (may prevent Hip Fractures)

14. Obstructive Pulmonary Disease (COPD or

Asthma) 1. Avoid Beta Blockers

15. Perioperative Hypertension 1. Beta Blockers should be use preventively

2. Delay surgery until BP <180/110

16. Edema 1. Avoid Calcium Channel Blockers

17. Peripheral Vascular Disease 1. These patients are high risk for cardiovascular event

2. Calcium Channel Blocker

3. Beta Blockers may be tolerated

1. Previously thought to be

contraindicated

18. Peptic Ulcer Disease 1. Avoid Calcium Channel Blockers

2. Gastrointestinal Bleeding risk

19. Neurologic and psychiatric disorders 1. Essential Tremor

1. Noncardioselective Beta Blocker

2. Migraine Headache 1. Noncardioselective Beta-Blockers

2. Nondihydropyridine calcium antagonists

3. Major Depression 1. Avoid Beta Blockers

4. Substance Abuse 1. Labetolol (Combined alpha-Beta Blocker)

2. Calcium Channel Blockers

3. Nitrates

Hypertension Management

1. See Also 1. Hypertension

2. Hypertension Criteria

3. Hypertension Evaluation

4. Hypertension Risk Stratification

2. General Guidelines 1. See patients back at one month after

starting agent 1. Significantly improves compliance

2. BP requires 1 month on agent to equilibrate

2. Maximize compliance 1. Work with patients to reduce adverse effects

2. Switch to other agents if adverse effects

significant

3. Do not be overzealous 1. Risk of overcorrection of Blood Pressure

2. Avoid lowering diastolic pressure <70 mmHg

3. Greater tolerance for elevated BP with

increased age

1. Study of 484 Swedish men over

70 from 1982-1992

2. Risk if Diastolic Blood Pressure

lowered below 90

1. Increased cardiac

event risk 3.9x

2. Controlled for

confounding factors

3. Reference

1. Merlo (1996) BMJ

313:457

4. Medications that prevent Hypertension vascular sequelae

1. Beta-Blockers

2. Diuretics

3. ACE Inhibitors

4. Calcium Channel Blockers

5. Medications that prevent Left Ventricular Hypertrophy

1. Most effective at reduced LVH risk 1. ACE Inhibitors

2. Diuretics

3. Beta-Blockers

2. Least effective at reduced LVH risk 1. Prazosin

2. Clonidine

3. Diltiazem

3. Reference 1. Gottdiener (1997)

Circulation 95:2007

3. Management Protocol 1. See Hypertension Risk Stratification

2. See Hypertension Reduction Goal

4. Management Strategies 1. Hypertension General Measures

2. Antihypertensive Selection

3. Hypertension Combination Therapy

4. Hypertension Management for Specific Comorbid

Diseases

5. Hypertension Management for Specific Populations

6. Hypertension Management for Specific Emergencies

5. References 1. (2000) Lancet 356:1955

Hypertension Management for Specific Emergencies

Hypertensive Crisis, Malignant Hypertension

1. See Also 1. Hypertension

2. Hypertension Criteria

3. Hypertension Evaluation

4. Hypertension Management

5. Antihypertensive Selection

6. Resistant Hypertension

7. IV Antihypertensives

2. Hemorrhagic Stroke 1. Nitroprusside

2. Trimethaphan

3. Labetalol

3. Left Ventricular Heart Failure 1. Nitroprusside

2. Trimethaphan

3. Avoid labetalol

4. Myocardial Infarction or Myocardial Ischemia

1. Nitroglycerin Drip

2. Labetalol

5. Aortic Dissection 1. Trimethaphan

2. Nitroprusside

3. Propranolol

6. Pheochromocytoma 1. Phentolamine

2. Avoid Beta Blockers

7. Preeclampsia or Eclampsia 1. Magnesium Sulfate

2. Hydralazine

Hypertension Risk Stratification

= Hypertension Risk Group A, Hypertension Risk Group B,

Hypertension Risk Group C

1. See Also 1. Hypertension

2. Hypertension Evaluation

3. Hypertension Management

2. Indication 1. JNC VII Guide for Hypertension Intervention

3. Risk Group A: Low Cardiovascular Risk 1. Criteria

1. No Cardiovascular Risks (See Risk Group B)

2. No Target organ damage or Cardiovascular

Disease

2. Prehypertension (120-139 / 80-89) 1. Lifestyle Modification in Hypertension

3. Stage 1 Hypertension (140-159 / 90-99) 1. Lifestyle Modification in Hypertension

2. Consider Antihypertensive after up to 6-12 months

1. Hydrochlorothiazide first choice in

most patients

4. Stage 2 Hypertension or greater (>159/99) 1. Lifestyle Modification in Hypertension

2. Hypertension Combination Therapy

4. Risk Group B: Moderate Cardiovascular Risk

1. Criteria 1. Tobacco Abuse

2. Dyslipidemia

3. Renal insufficiency

4. Patient age over 60 years

5. Male gender of postmenopausal women

6. Cardiovascular Family History

7. No Diabetes Mellitus

8. No Target organ damage or Cardiovascular

Disease

2. Prehypertension (120-139 / 80-89) 1. Lifestyle Modification in Hypertension

3. Stage 1 Hypertension (140-159 / 90-99) 1. Lifestyle Modification in Hypertension

2. Antihypertensive (e.g. Hydrochlorothiazide)

4. Stage 2 Hypertension or greater (>159/99) 1. Lifestyle Modification in Hypertension

2. Hypertension Combination Therapy

5. Risk Group C: High Cardiovascular Risk 1. Criteria

1.

Target organ damage or Cardiovascular Disease

1. Left Ventricular Hypertrophy

2. Angina or prior Myocardial

Infarction

3. Prior coronary revascularization

4. Cerebrovascular Accident (Stroke

or CVA)

5. Transient Ischemic Attack (TIA)

6. Nephropathy or Chronic Kidney

Disease

7. Peripheral Vascular Disease

8. Retinopathy

2. Cardiovascular Risks (See Risk Group B)

2. Prehypertension (120-139 / 80-89) or greater

1. Lifestyle Modification in Hypertension

2. Antihypertensive 3. Hypertension Combination Therapy

if >20/10 over goal

6. References 1. (1997) Arch Intern Med 157:2413 2. Chobanian (2003) JAMA 289:2560

Refractory Hypertensive Populations

1. See Also 1. Hypertension

2. Hypertension Criteria

3. Hypertension Evaluation

4. Hypertension Management

5. Antihypertensive Selection

6. Resistant Hypertension

2. Populations with Hypertension that is difficult to treat

1. African-American

2. Hispanic

3. Diabetes Mellitus

4. Renal Insufficiency or Renal Failure

5. Elderly (especially Isolated Systolic Hypertension)

6. Stage 3 Hypertension or greater

7. Obese Patients

3. Protocol 1. Consider Hypertension Combination Therapy

Hypertension Criteria

= Hypertension Reduction Goal, High-Normal Blood

Pressure, Stage 1 Hypertension, Stage 2 Hypertension, Stage 3 Hypertension, Stage 4 Hypertension

1. Criteria: Hypertension in Adults 1. Goal Blood Pressures for Hypertensive

Patients

1. Hypertension without Co-morbidity: <140/90

2. Diabetes Mellitus: <130/80

3. Congestive Heart Failure: <130/80

4. Renal Insufficiency: <130/80

5. Renal Failure and >1g Proteinuria/24 hours:

<125/75

2. JNC-7 Blood Pressure definitions 1. Optimal Blood Pressure: <115/80

2. Normal Blood Pressure: <120/80

3. Pre-Hypertension: 120-139/80-89

4. Stage 1 Hypertension: 140-159/90-99

5. Stage 2 Hypertension: >160/100

3. Stages eliminated in JNC-7 1. Stage 3 Hypertension: 180-209/110-119

2. Stage 4 Hypertension: >210/120

4. Isolated Systolic Hypertension 1. Systolic Blood Pressure: >140 mmHg

2. Diastolic Blood Pressure: <90 mmHg

2. Criteria: Hypertension in Adolescents 1. Age 16-18 years

1. Significant Hypertension: BP> 142/92

2. Severe Hypertension: BP> 150/98

2. Age: 13-15 years 1. Significant Hypertension: BP> 136/86

2. Severe Hypertension: BP> 144/92

3. Criteria: Hypertension in Children 1. Age 10-12 years

1. Significant Hypertension: BP> 126/82

2. Severe Hypertension: BP> 134/90

2. Age 6-9 years 1. Significant Hypertension: BP> 122/78

2. Severe Hypertension: BP> 130/86

3. Age 3-5 years 1. Significant Hypertension: BP> 116/76

2. Severe Hypertension: BP> 124/84

4. Criteria: Hypertension in Infants (Age <2 years) 1. Significant Hypertension: BP> 112/74

2. Severe Hypertension: BP> 118/82

5. Criteria: Hypertension in Newborns 1. Age 8-30 days

1. Significant Hypertension: SBP> 104

2. Severe Hypertension: SBP> 110

2. Age <7 day old 1. Significant Hypertension: SBP> 96

2. Severe Hypertension: SBP> 106

6. Reference 1. (1987) Pediatrics 79(1):1 2. (1997) Arch Intern Med 157:2413 3. (2000) NKF Consensus Report

Hypertension in Diabetes Mellitus

= Diabetes Mellitus Associated Hypertension

1. See Also 1. Diabetes Mellitus

2. Hypertension

3. Hypertension Management

4. Nonpharmacologic Management of Hypertension

5. DASH Diet

2. Management: Blood Pressure Goal 1. Continue adding agents until goal reached (2 or 3 at a

time are the norm)

2. Small differences in Blood Pressure (5 mmHg) have

large impact on outcomes

3. Adults: <130/80 mmHg (ideal Blood Pressure is

115/75)

4. Child: Average <95th percentile based on height,

gender and age

1. See Pediatric Hypertension

2. See Hypertension Criteria

3. NIH Information on Hypertension in Children

1. http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.pdf

3. Complications: Hypertension adverse effects in Diabetes Mellitus

1. Microvascular Complications 1. Renal insufficiency (and Proteinuria)

1. ACE Inhibitors beneficial (except

renal stenosis)

2. Calcium Channel Blockers

beneficial

3. Angiotensin Receptor Blockers

beneficial

2. Autonomic Neuropathy (e.g. Impotence)

3. Diabetic Retinopathy

2. Macrovascular Complications 1. Coronary Artery Disease

1. ACE Inhibitors beneficial

2. Thiazide Diuretics beneficial

3. Long-acting Calcium Channel

Blockers beneficial

1. Nondihydropyridines clearly are beneficial

2. Mixed data on Dihydropyridines

(e.g. Verapamil) 4. Beta Blockers beneficial

2. Cerebrovascular Disease 1. ACE Inhibitors beneficial

2. Thiazide Diuretics beneficial

3. Peripheral Vascular Disease

4. Management: Medications 1. First-Line Agents

1. ACE Inhibitor

1. Increases Glomerular Filtration

Rate (GFR)

2. Decreases Proteinuria

2. Angiotension II Receptor Blockers

1. Alternative to ACE Inhibitors

2. Second-Line Agents 1. Diuretics (especially in Isolated Systolic

Hypertension)

3. Third-Line Agents 1. Beta Blockers

1. Now thought to be a viable option

for Hypertension control

2. Historically has been used only

when other options have been

exhausted

1. Blunts hypoglycemic

response (not seen in

studies)

2. Associated with

increased weight gain

3. Glucose and lipids less

affected with Carvedilol

2. Calcium Channel Blockers

1. Non-Dihydropyridine Calcium

Channel Blockers

2. Dihydropyridine Calcium Channel

Blockers

4. Other Medications 1. Alpha antagonists (use only as adjunctive

agent)

5. Management: Algorithm 1. General

1. See Hypertension Management

2. See Nonpharmacologic Management of

Hypertension

3. See DASH Diet

2. Protocol 1. Start with 2 medications if goal is >20 mmHg

lower than current Blood Pressure

2. Anticipate needing as many as 3-4

antihypertensives to reach goal

3. Adjust in specific populations (e.g. Black)

1. See Antihypertensives for Specific

Populations

2. May require ACE Inhibitor for renal

protection, but other agents for

Blood Pressure control

3. Step 1: Start with ACE Inhibitor or Angiotensin Receptor Blocker (ARB)

1. Proteinuria present: Evidence supports

ACE/ARB as first line

2. Proteinuria absent: No evidence for one

antihypertensive class over another

4. Step 2: Add Diuretic 1. Serum Creatinine >1.8: Loop Diuretic (e.g.

Furosemide)

2. Serum Creatinine <1.8: Thiazide Diuretic

1. Hydrochlorothiazide

2. Chlorthalidone (may be preferred)

1. Longer half-life (better

24 hour control)

2. Approaches twice the

potency of

Hydrochlorothiazide

5. Step 3: Add long-acting Calcium Channel Blocker

1. Dihydropyridine Calcium Channel Blocker

(e.g. Norvasc, Nifedipine) or

2. Non-Dihydropyridine Calcium Channel

Blocker (e.g. Verapamil, Diltiazem) or

1. Do not use with Beta Blocker

6. Step 4: Add Beta Blocker 1. Use caution if Heart Rate <70-80 bpm

2. Avoid if on Non-Dihydropyridine Calcium

Channel Blocker (e.g. Verapamil, Diltiazem)

7. Step 5: Add additional antihypertensive 1. Central Adrenergic Agonist (e.g. Clonidine)

2. Alpha Adrenergic Antagonist (e.g. Hytrin)

3. Reserpine (very effective per JNC7, but

review drug interactions)

6. References 1. (2003) Diabetes Care 26:S80

2. () Arauz-Pacheco Diabetes Care 27:S65

3. Fineberg (1999) Prim Care 26:951

4. Konzem (2002) Am Fam Physician 66(7):1209

5. Whalen (2008) Am Fam Physician 78(11):1277

Renin-Angiotensin System

= Renin, Angiotensin, Angiotensinogen, Angiotensin Converting Enzyme

1. Physiology: Overall Process 1. Step 1: Renin release

1. Stimulators of renin release 1. Kidney detects decreased

effective blood flow

2. Increased sympathetic tone

3. Renal Artery Stenosis

2. Renin secreted from renal cortex 1. Secreted from juxtaglomerular

cells

2. Cells located at afferent arteriole

of glomerulus

2. Step 2: Renin mediated step 1. Renin cleaves angiotensinogen to

Angiotensin I

3. Step 3: Angiotensin-converting enzyme (ACE) mediated

1. Angiotensin I converted by ACE to

Angiotensin II

2. Conversion by ACE occurs in pulmonary

vasculature

4. Step 4: Angiotensin II Effects 1. Sodium and water retention

1. Stimulates aldosterone secretion

2. Directly affects renal tubule

2. Vasomotor tone balance 1. Angiotensin II is a potent

vasoconstrictor

1. Increases systemic

vascular resistence

2. May be Norepinephrine

mediated

2. Antagonist to nitric oxide (potent

vasodilator)

2. Physiology: Angiotensin II Effects 1. Increases oxygen demand

2. Increases coronary and renal vasoconstriction

3. Increases preload and afterload

4. Predisposes to Left Ventricular Hypertrophy

5. Increases Catecholamine release (e.g.

Norepinephrine)

6. Increases aldosterone

3. Agents that decrease Angiotensin II levels 1. ACE Inhibitors

2. Angiotensin Receptor Blocker

4. References 1. Rose (1987) Pathophysiology of Renal

Disease, p. 474-7 2. Bicket (2002) Am Fam Physician 66(3):461

Hypertension in the Elderly

1. See Also 1. Hypertension

2. Hypertension Criteria

3. Hypertension Evaluation

4. Hypertension Management

5. Antihypertensive Selection

6. Isolated Systolic Hypertension

7. Hypertension Management for Specific Comorbid

Diseases

2. Pathophysiology: Vascular changes seen in the elderly

1. Increased vascular resistance

2. Reduced plasma renin activity

3. Increased Left Ventricular Hypertrophy

3. Exam 1. See Hypertension Criteria

2. See Hypertension Evaluation

4. Pitfalls in the elderly 1. Pseudohypertension occurs due to calcified arteries

1. Calcified arteries are more difficult to

compress

2. Isolated Systolic Hypertension is common in elderly

1. Treat aggressively if systolic BP >139

3. Consider Ambulatory Blood Pressure Monitoring

1. May better identify hypotensive episodes

4. Consider two antihypertensives if SBP >160 or

DBP>100

5. Management: First-Line Antihypertensives 1. Thiazide Diuretics are the preferred antihypertensive

2. Thazide Diuretics decrease morbidity and mortality

1. Cerebrovascular Accident

2. Congestive Heart Failure

3. Myocardial Infarction

3. Observe closely for adverse effects in elderly

1. Dehydration

2. Orthostatic Hypotension

3. Hypokalemia

1. Check Serum Potassium

frequently

2. Consider combining with

Potassium-Sparing Diuretic

6. Management: Second-Line Antihypertensives

1. Beta Blockers 1. Reduce morbidity and mortality in the elderly

2. Consider in vascular disease and CHF

3. Use specific agents: Atenolol, Metoprolol

2. ACE Inhibitors or Angiotensin Receptor Blocker

1. Consider in CAD, CVA, CHF, Diabetes, CRF

2. Observe closely for adverse effects

1. Dehydration or decreased

circulatory volume

2. Heart Failure

3. Renal Artery Stenosis

3. Calcium Channel Blockers 1. Consider in Coronary Disease and Diabetes

Mellitus

2. Consider in black and salt-sensitive patients

3. Observe for Orthostatic Hypotension with

Nifedipine

4. Avoid short-acting agents

7. Use with caution: Central alpha agonists (e.g. Clonidine)

1. These agents do not reduce morbidity or mortality

2. Adverse effects are more common in the elderly

1. Sedation

2. Dry Mouth

3. Depressed mood

4. Hypotension

5. Rebound Hypertension if abruptly stopped

8. References 1. Chobanian (2003) {a 531} 42:1206 2. Dickerson (2005) Am Fam Physician

71(3):469

Hypertension in Infants

= Hypertension in Newborns, Neonatal Hypertension

1. See Also 1. Hypertension in Children 2. Hypertension

2. Normal Blood Pressures in young infants and newborns

1. See Pediatric Vital Signs

3. Causes 1. See Hypertension Causes

2. Blood Pressure higher in upper extremity 1. Aortic Coarctation

2. Interrupted aortic arch

3. Blood Pressure higher in lower extremity 1. Renal parenchymal disease

2. Endocrine abnormality

3. Neonatal Seizures with transient

Hypertension

4. Hypervolemia

5. Renovascular (Umbilical Artery Catheter

complication)

1. Aortic mural thrombi

2. Renal artery thrombosis

3. Renal vein thrombosis

4. Evaluation 1. Aortic cause suspected

1. Evaluate for Aortic Coarctation

2. Renal or endocrine cause suspected

1. Serum electrolytes with Renal Function tests

(Chem8)

2. Plasma renin

3. Renal Ultrasound with doppler flow

3. CNS cause suspected

1. CT or MRI Head

5. References 1. Bada in Korones (1993) Neonatal Decision

Making, p. 152 2. Ingelfinger (1982) Pediatric Hypertension, p.

229-240 3. Ingelfinger in Cloherty (1991) Neonatal

Care, p. 492-5 4. Fuloria (2002) Am Fam Physician 65(1):61

Blood Pressure Control after Cerebrovascular Accident

= Stroke Related Blood Pressure Management, CVA

Blood Pressure Control

1. General 1. Avoid lowering Blood Pressure too low in acute CVA

1. Lower Blood Pressure correlates with lower

perfusion

2. Goal Blood Pressure: 120% of baseline Blood

Pressure

2. Absolute indications for BP intervention in acute CVA

1. Blood Pressure >220/120

2. Acute Myocardial Infarction

3. Hypertensive encephalopathy

4. Renal Failure

5. Aortic Dissection

6. Retinal hemorrhage

3. Emergent Hypertensive Crisis 1. Criteria

1. Diastolic Blood Pressure exceeds 140

mmHg

2. Confirmed on 2 readings, 5 minutes apart

2. Management

1. Start Nitroprusside Infusion

4. Severe Hypertensive Crisis 1. Criteria

1. Systolic Blood Pressure >230 or

2. Diastolic Blood Pressure 121 to 140

3. Confirmed on 2 readings, 20 minutes apart

2. Management 1. Labetolol 20 IV over 1-2 minutes

1. May repeat dose or double dose

every 10-20 minutes

2. Subsequent Labetolol doses given

every 6-8 hours

2. Endpoints 1. Satisfactory Blood Pressure

2. Maximum dose reached of 300 mg

Labetolol

3. Relative contraindications 1. Asthma

2. Congestive Heart Failure

3. Arrythmias

5. Moderate Hypertensive Crisis 1. Criteria

1. Systolic Blood Pressure 180 to 230 or

2. Diastolic Blood Pressure 105 to 120 and

3. Signs of end-organ consequences

1. Subarachnoid Hemorrhage or

2. Congestive Heart Failure

4. Confirm on 2 readings, 60 minutes apart

2. Management 1. Labetolol 200-300 PO bid to tid or

2. Nifedipine 10 mg PO q6h or

3. Captopril 6.25-25 q8h

4. Nimodipine 60 mg PO q4h

1. Used in Subarachnoid

Hemorrhage

5. Labetolol IV

1. Indicated for refractory to oral

interventions

6. Angiotensin Receptor Blocker (ARB)

1. Started on day 1 if Hypertension

with Ischemic CVA

1. Two BPs >200/100 at 6

to 24 hours post-CVA or

2. Two BPs >180/105 at

24 to 36 hours post-CVA

2. Significantly reduced recurrent

CVA risk

1. Schrader (2003) Stroke

34:1699

6. Controlled Hypertensive Crisis 1. Criteria

1. Systolic Blood Pressure <180 or

2. Diastolic Blood Pressure < 105

2. Management 1. No antihypertensive routinely recommended

2. Concurrent Heparin use

1. Carefully titrate down Blood

Pressure

2. Target levels if no prior

Hypertension

1. Systolic Blood Pressure:

150

2. Diastolic Blood

Pressure: 85 to 95

3. Target levels if prior Hypertension

1. Systolic Blood Pressure:

160 to 170

2. Diastolic Blood

Pressure: 90 to 100

4. Benefits of Heparin are very

contoversial

1. DO not rapidly lower BP

to start Heparin

7. References 1. Lisk (1993) Arch Neurol 50:855 2. Powers (1993) Neurology 43:461

Hypertension in Children

= Hypertension in Adolescents, Pediatric Hypertension

1. See Also 1. Hypertension in Infants 2. Hypertension

2. Criteria 1. See Hypertension Criteria 2. Routine Blood Pressure screening over age

3 years

3. Causes 1. See Hypertension Causes in Children

2. Renovascular disease is most common

cause in children

3. Features most suggestive of secondary

Hypertension

1. Hypertension under age 10 years

2. Stage 2 Hypertension in children

4. Risk Factors 1. Obesity or Metabolic Syndrome

2. Black ethnicity

3. Snoring or other findings of Sleep Apnea

4. Family History

1. CAD, Hyperlipidemia or htn: Essential

Hypertension

2. Kidney disease or deafness: Renovascular

disease

3. Diabetes, Thyroid or adrenal disease:

Endocrinopathy

5. History 1. See Family History above

2. See Medication Causes of Hypertension

3. General: Weight change

4. Lung: Dyspnea on exertion

5. Cardiovascular: Chest Pain, Palpitations

6. Renal: Hematuria, Recurrent Urinary Tract

Infection

7. Extremities: Edema, joint pain or swelling,

myalgias

8. Neurologic: Headaches

9. Endocrine: Profuse sweating, hot or cold

intollerance

6. Examination: Secondary Hypertension clues 1. General

1. Growth delay (Chronic Kidney Disease)

2. Eyes 1. Fundoscopic exam

3. Throat 1. Tonsil or adenoid hypertrophy (Sleep Apnea)

4. Neck 1. Thyromegaly (Hyperthyroidism)

5. Cardiovascular 1. Tachycardia (Hyperthyroidism,

Pheochromocytoma)

6. Abdomen 1. Abdominal mass (renal lesion)

2. Abdominal bruit (Renal Artery Stenosis)

7. Extremities 1. Cold legs with diminished pulses (Aortic

Coarctation)

2. Joint swelling (Systemic Lupus

Erythematosus)

8. Skin 1. Acne Vulgaris, Hirsutism (Cushing's

Disease)

2. Malar Rash (Systemic Lupus

Erythematosus)

3. Profuse sweating (Pheochromocytoma)

9. Neurologic 1. Motor weakness (Hyperaldosteronism)

10. Endocrine 1. Truncal Obesity, moon facies (Cushing's

Syndrome)

7. Diagnosis 1. See Hypertension Criteria

2. Obtain 3 elevated Blood Pressures on different days

3. Consider Ambulatory Blood Pressure Monitoring

8. Labs 1. Complete Blood Count

1. Includes Leukocyte differential and Platelet Count

2. Chemistry panel 1. Electrolytes

2. Serum Glucose (consider obtaining with

Insulin)

3. Blood Urea Nitrogen

4. Serum Creatinine

5. Serum Calcium

6. Serum Phosphorus

7. Serum Uric Acid

3. Urine testing 1. Urinalysis

2. Urine drug screen (if indicated)

3. Urine Culture

4. Consider 24 hour urine

1. Creatine clearance

2. 24 Hour Urine Protein Collection

4. Endocrine tests 1. Thyroid Stimulating Hormone (TSH)

2. Consider 24 hour Urine Cortisol

3. Consider plasma renin level

4. Consider 24 hour Urine VMA and

metanephrines

9. Diagnostics 1. Electrocardiogram 2. Other studies to consider

1. Echocardiogram 2. MRA of renal arteries

10. Imaging 1. Renal ultrasound

11. Management: Non-pharmacologic 1. Weight loss if overweight

2. Regular Exercise program

3. Low Fat Diet

4. Low sodium diet (e.g. DASH Diet)

5. Tobacco Cessation

6. Avoid Alcohol

12. Management: Pharmacologic 1. Indications

1. Symptomatic Hypertension

2. Secondary Hypertension

3. Stage 1 Hypertension refractory to general

measures

4. Stage 2 Hypertension

5. End-organ involvement

1. Proteinuria

2. Retinopathy

3. Left Ventricular Hypertrophy

2. Goal Blood Pressures 1. Less than 95%: No end organ damage

2. Less than 90%: End-organ involvement or

comorbidity

3. Agents FDA approved in children 1. Propranolol 1-2 mg/kg/day (max: 4

mg/kg, 640 mg)

2. Hydrochlorothiazide 1 mg/kg/day (max: 3 mg/kg, 50 mg)

3. Amlodipine 2.5 to 5 mg/day (max: 10 mg/day)

4. ACE Inhibitors (age 6 and over) 1. Lisinopril 0.07 mg/kg/day

(max: 0.6/mg/kg, 40 mg) 2. Benzapril, Enalapril,

Fusinopril also FDA approved

5. Angiotensin Receptor Blockers (age 6 and over)

1. Losartan 0.7 mg/kg/day (max: 1.4 mg/kg, 100 mg)

2. Irbesartan (Avapro) also FDA approved

1. Ages 6-12 are given 75 to 150 mg daily maximum

2. Age 13 and older are given adult dosing

13. References 1. (2004) Pediatrics 114:555 2. Bartosh (1999) Pediatr Clin North Am

46:235 3. Flynn (2005) Adolesc Med Clin 16:11 4. Luma (2006) Am Fam Physician 73(9):1558

Funduscopic Changes in Hypertension

= Retinal Changes in Hypertension, Keith-Wagner

1. See Also 1. Hypertension

2. Technique 1. Dilate eye (Mydriacyl)

3. Grading of Hypertensive funduscopic changes 1. GP 1

1. Spasm of retinal vessels

2. GP 2 1. Constriction and sclerosis of retinal arterioles

2. Arteriovenous Nicking (AV Nicking) of retinal

vessels

3. GP 3 1. Vascular changes

2. Hemorrhages

3. Exudates

4. GP 4 1. Above changes & Papilledema

Spasm of retinal vessels

Constriction and sclerosis of retinal arterioles

AV Nicking

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