Hypertension and dyslipidemia

(LIPITENSION)

KCS – BOMA ELDORETAKWANALO C

Cardiologist

Outline

• Introduction • Definitions • Prevalence • Interplay: Lipitension and atherosclerosis

– Dyslipidemia – Hypertension 

• Microalbuminuria 

• Management • Conclusions 

Introduction 

• Cardiovascular diseases: leading cause of mortality

• Hypertension and dyslipidemia: 2 major risk factors: adverse effects are additive

• Prevalence of co‐existence : 15 ‐ 31%

410

285

70 5935

461

265

64 47 38

0

100

200

300

400

500

A B C D E A B D F E

MalesFemales

Deaths in Thousands

A Total CVDB CancerC Accidents

D Chronic Lower Respiratory DiseasesE Diabetes MellitusF Alzheimer’s Disease

Leading causes of death for all males and females

(United States: 2004). Source: NCHS and NHLBI.

Percentage breakdown of deaths from cardiovascular diseases (United States:2004) Source: NCHS and NHLBI.

17%6%

13%

7%4%

52%

.4% .5%Coronary Heart DiseaseHeart FailureDiseases of the ArteriesDefectsRheumatic Fever/Rheumatic Heart Disease

StrokeHigh Blood PressureCongenital CardiovascularOther

Definitions 

• Dyslipidemic hypertension (DH)

– Familial DH: Genetic syndrome 

• 12% of patients with essential hypertension

• 48% of hypertension sibships

• Lipitension: ease of identification

Levels of Risk Associated with Smoking, Hypertension and Hypercholesterolaemia

x1.6x1.6 x4x4

x3x3

x6x6

x16x16x4.5x4.5 x9x9

Hypertension(SBP 195 mmHg)Hypertension

(SBP 195 mmHg)

Serum cholesterol level(8.5 mmol/L, 330 mg/dL)Serum cholesterol level(8.5 mmol/L, 330 mg/dL)

SmokingSmoking

Adapted from Poulter N et al., 1993Adapted from Poulter N et al., 1993

Prevalence • Increases with age

– < 40 years, < 2%– > 40 years, 31 – 56%

• Women > men (20 vs. 16 %)• Racial variation

– Lowest in Hispanics (9.6%)– Highest in African Americans (22%)

• Increases with increasing risk factor burden– Highest in CVD + DM– Metabolic syndrome 

Interplay: Lipitension and atherosclerosis

• Dyslipidemia– Endothelial injury

• Manifest as ASCVD

– Physiologic vasomotor dysfunction• Manifest as hypertension**

– Direct relation between hypertension and CV events 

HDL-C vs LDL-C as a predictor of CHD risk

*Men aged 50–70 Gordon, Castelli et al. Am J Med 1977; 62: 707–714Gordon, Castelli et al. Am J Med 1977; 62: 707–714

100 mg/dl 160 mg/dl 220 mg/dl0

0.5

1

1.5

2

2.5

3

Risk of CAD over 4years of follow-up*

LDL-C

85 mg/dl65 mg/dl

45 mg/dl25 mg/dl

CHD RR

HDL-C

CHD Risk According to HDL-C LevelsFramingham Study4.0

3.0

2.0

1.0

25 45 65HDL-C (mg/dL)

CH

D r

isk

ratio

Kannel WB. Am J Cardiol 1983;52:9B–12B

2.0

1.0

0

4.0

Relative risks of MI

3.21

3.78

1.002.41 Low HDL cholesterol

<47 mg/dl

High HDL cholesterol47 mg/dl

Low total cholesterol<212 mg/dl

High total cholesterol212 mg/dl

Stampfer, Sacks et al. N Engl J Med 1991; 325: 373–381Stampfer, Sacks et al. N Engl J Med 1991; 325: 373–381

The Physicians Health Study

Serum Cholesterol

Age: 35-64* Age: 65-94

MenWome

n Men+ Women*84-204 8 4 22 11

205-234 13 5 24 15

235-264 14 4 26 17

265-294 15 7 23 17

295-1124 26 10 38 32

Risk of Coronary Heart Diseaseby Serum Cholesterol

30-Year Follow-up, The Framingham Study

*Trends Significant at P.001. +P.07.

Age-Adjusted Annual Rate per 1000

Lifetime Risk of CHD Increases with Serum Cholesterol

0

10

20

30

40

50

60

Perc

ent

Men Women

<200 mg200-239 mg>240 mg

Framingham Study: Subjects age 40 years

DM Lloyd‐Jones et al Arch Intern Med 2003; 1966‐1972

34

44

57

19

2933

Cholesterol

___________________________________________________________________________

_______________________________________________________________________________

Effects of TC Levels on the Risk for CHD in the Presence of Other Risk Factors

Low HDL

Smoking

Hyperglycemia

Hypertension

No Other Risk Factors

Schaefer EJ, adapted from the Framingham Heart Study

Serum Cholesterol (mg/dL)

MRFIT ‐ Study

Q = serum cholesterol quintile.Kannel WB et al. Am Heart J. 1986;112:825-836.

Multiple Risk Factor Intervention Trial (MRFIT) N=325,346

Correlation Between Serum       Cholesterol and CVD Mortality

6-Ye

ar C

VD D

eath

Rat

e Pe

r 100

0

0

5

10

15

20

25

30

Q1(<182)

Q2(182-202)

Q3(203-220)

Q4(221-244)

Q5(>244)

35-39 years

40-44 years

45-49 years

50-54 years

55-57 years

Serum Cholesterol Quintile (mg/dL)

Untreated Patients

Lipid Research council 

0

5

10

15

20

25

30

(2.60) (3.25)(3.90)(4.50) (5.15) (5.80)(6.45) (7.10) (7.75) (8.40)(9.05)

Cholesterol and CHD: Seven Countries Study

TC mg/dL (mmol/L)

CHDmortality rates

(%)

Verschuren WMM et al. JAMA. 1995;274:131-136.

100 125 150 175 200 225 250 275 300 325 350

Northern EuropeUnited StatesSouthern Europe, InlandSouthern Europe, MediterraneanSiberiaJapan

Lipitension and atherosclerosis• Hypertension 

– Abnormal RAAS• Ag‐II promotes atherogensis via AT‐1 Receptor

– Increased lipid uptake by cells– Vasoconstriction– Free radicals production

– Altered shear stress and oxidative stress• Overproduction of collagen and fibronectin• Decreases NO‐dependent vascular relaxation• Increased permeability of lipoproteins• Up‐regulation of lipid oxidation enzymes

Relation of Non‐Hypertensive Blood  Pressure to Cardiovascular Disease

Vasan R, et al. N Engl J Med 2001; 345:1291‐1297

0%

2%

4%

6%

8%

10%

12%

Women Men

<120/80 mm Hg120-129/80-84 mm Hg130-139/85-89 mm Hg

10‐year Age‐ Adjusted Cumulative Incidence

Hazard Ratio*

SBP Women Men

<120/80 1.0      1.0 120‐129        1.5      1.3  130‐139        2.5      1.6

H.R. adjusted for age, BMI, Cholesterol, Diabetes and smoking *P<.001

Framingham Study: Subjects Ages 35‐90 yrs. 

1.92.8

4.4

5.8

7.6

10.1

Lipitension and atherosclerosis

• Hypertension– Micro‐albuminuria

• A marker glomerular function

• Predictor of CAD– Associated with dyslipidemia

» Decreased HDL‐C

» Increased LDL‐C

» Increased lipoprotein (a)

Management 

• Intuitive ?– Treatment of two RF equates additive benefits?

• Control of CVD risk factors inadequate– Overall: target not achieved in 50.2% (NHANES‐2001‐2002)

• Multiple RF interventions?– Incongruent results!

2o Prevention of Stroke: Percentage Prevented per Year

Straus SE, et al. JAMA. 2002;288:1388-1395.

0 2 4 6 8 10 12 14 16 18% of strokes prevented/yr

AntihypertensivesClopidogrel vs. ASA

WarfarinStatins

Smoking CessationAspirin

Carotid Endarterectomy

Key Statin Trials and Spectrum of Risk

4S14S1

LIPID2LIPID2

CARE4CARE4

WOSCOPS6WOSCOPS6

AFCAPS/TexCAPS7AFCAPS/TexCAPS7

CHD/high cholesterolCHD/high cholesterol

CHD/average to high cholesterolCHD/average to high cholesterol

CHD/average cholesterolCHD/average cholesterol

No MI/high cholesterolNo MI/high cholesterol

No CHD/average cholesterolNo CHD/average cholesterol

HPS3HPS3 CHD*/average to high cholesterolCHD*/average to high cholesterol

*CHD or CHD risk equivalent, e.g. diabetes*CHD or CHD risk equivalent, e.g. diabetes

Increasing absolute CHD risk

Increasing absolute CHD risk

ASCOT‐LLA5ASCOT‐LLA5 Some patients with CHD/average cholesterol

Some patients with CHD/average cholesterol

4S: Total Mortality

0.850.85

0.800.80

0.000.000.00.0

1.001.00

0.950.95

0.900.90

Prop

ortio

n al

ive

Prop

ortio

n al

ive

Years since randomisationYears since randomisation

placeboplacebosimvastatinsimvastatin

6644332211 55

Log rank p=0.0003Log rank p=0.0003

This improvement in survival is accounted for by the 42% reduction in coronary death.

This improvement in survival is accounted for by the 42% reduction in coronary death.

The Scandinavian Simvastatin Survival Study Group. Lancet 1994;344:1383–1389The Scandinavian Simvastatin Survival Study Group. Lancet 1994;344:1383–1389

The differential benefit of LDLc lowering in patients with diabetes has been evident from the earliest statin trials and is more evidence that higher risk=greater benefit : 4S study: Major Coronary

Events

11 22 33 44 55 6600

5050

6060

8080

9090

100100

55%55%

00

Diabetic – simvastatinDiabetic – placeboNondiabetic – simvastatinNondiabetic - placebo

Diabetic - simvastatin

Diabetic - placebo p=0.002Risk reduction

Coronary Death and non-fatal MI

Years since randomizationPyörälä K, et al. Diabetes Care. 1997;20:614–620

Perc

ent o

f pat

ient

s w

ithou

t maj

or C

V e

vent

7070

WOSCOPS: Non-fatal MI and CHD Death

YearsYears

00

11

22

44

66

Percent w

ith event

Percent w

ith event

88

1010

1212

22 3 3  44 55 66

pravastatin (n=3302)pravastatin (n=3302)placebo (n=3293)placebo (n=3293)

31% relativerisk reductionp<0.001

31% relativerisk reductionp<0.001

Shepherd J  et al. N Engl J Med 1995;333:1301–1307Shepherd J  et al. N Engl J Med 1995;333:1301–1307

Meta-analysis of 38 primary and secondary intervention trials Meta-analysis of 38 primary and secondary intervention trials

Benefits of Cholesterol Lowering

Total mortality (p=0.004)Total mortality (p=0.004)

CHD mortality (p=0.012)CHD mortality (p=0.012)

% in cholesterol reduction% in cholesterol reduction

Mor

talit

y lo

g od

ds r

atio

Mor

talit

y lo

g od

ds r

atio

00 44 88 1212 1616 2020 2424 2828 3232 3636‐1.0‐1.0

‐0.8‐0.8

‐0.6‐0.6

‐0.4‐0.4

‐0.2‐0.2

‐0.0‐0.0

4040 4444 4848 5252

Adapted from Gould AL et al. Circulation. 1998;97:946–952Adapted from Gould AL et al. Circulation. 1998;97:946–952

-60

-50

-40

-30

-20

-10

0

10

79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95

Change In Age‐Adjusted Mortality1979 ‐ 1995

%Decline

National Center for Health Statistics.

Noncardiovascular Disease

Coronary Heart Disease

Stroke

Effects of lipid lowering on BP

• If on ACE‐I, potentiation? 

– Pleotropic effects

– Correction of dyslipidemia

• Not replicable

Effects BP lowering on dyslipidemia

• B‐blockers: B‐1 selective; little effect

• Thiazides: significant effect at high doses

• Preferred: CCB, A‐blockers, RAAS blockers 

9

Doubts about  cholesterol as late as 1989

Vascular Protection Checklist2013

A • A1C – optimal glycemic control (usually ≤7%) B • BP – optimal blood pressure control (<130/80) C • Cholesterol – LDL ≤2.0 mmol/L if decided to

treat D • Drugs to protect the heart (regardless of baseline BP or LDL)

A – ACEi or ARB │ S – Statin │ A – ASA if indicated

E • Exercise / Eating healthily – regular physical activity, achieve and maintain healthy body weight

S • Smoking cessation

http://clincalc.com/Cardiology/ASCVD/PooledCohort.aspx

Conclusions

• Lipitension : important RF for CVD

• LDL < 70 mg/dl and SBP< 120 mmHg is associated with % progress in atheroma

• Interplay mainly at vascular endothelial level

• Global risk assessment mandatory   

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