Lipoatrophy and lipohypertrophy are independently associated with hypertension: the effect of lipoatrophy but not lipohypertrophy on hypertension is independent of obesity

Heidi M. Crane1, MD, MPH, Carl Grunfeld2, MD, PhD, Robert D. Harrington1, MD, and Mari M. Kitahata1, MD, MPH

From the Departments of Medicine, University of Washington1, Seattle, WA and University of California2, San Francisco, CA

Lipoatrophy and lipohypertrophy are independently associated with hypertension: the effect of lipoatrophy but not lipohypertrophy on hypertension is independent of obesity

Heidi M. Crane1, MD, MPH, Carl Grunfeld2, MD, PhD, Robert D. Harrington1, MD, and Mari M. Kitahata1, MD, MPH

From the Departments of Medicine, University of Washington1, Seattle, WA and University of California2, San Francisco, CA

Background Lipoatrophy (LA) and lipohypertrophy (LH) are associated

with metabolic abnormalities, but little is known about their impact on hypertension

Prior studies have been small, yielded conflicting findings, and did not examine LA and LH separately

We conducted this study to examine the independent association between LA and LH with hypertension among HIV-infected patients

Methods STUDY SETTING: Cross-sectional study of patients in the

University of Washington (UW) HIV Cohort, a longitudinal observational cohort of HIV-infected patients

STUDY SUBJECTS: Convenience sample of patients ≥18 years of age who attended the clinic for a routinely scheduled appointment between 9/26/05 and 1/3/07

DATA SOURCE: Patients used tablet PCs with touch screens to complete an assessment with body morphology (based on the Fat Redistribution and Metabolic Change [FRAM] instrument), smoking status, and illicit drug use

Data were also obtained from the UW HIV Information System (UWHIS) which captures comprehensive clinical data for the UW HIV cohort from 1995 to the present. Demographic, clinical, laboratory, medication, and socioeconomic data are obtained from multiple institutional data systems. Clinical patient data such as blood pressure (BP), height, and weight are routinely collected and integrated in the UWHIS

DEFINITION OF HYPERTENSION: We defined hypertension as a clinical diagnosis of hypertension confirmed by treatment with an antihypertensive medication, or a mean systolic BP >140 mmHg or diastolic BP >90 mmHg within the prior 6 months

BODY MORPHOLOGY: FRAM items for individual body regions were coded on a 7-point scale ranging from –3 to +3. No change was scored as 0, mild, moderate, and severe increases were scored as +1, +2, and +3, and mild, moderate, and severe decreases were scored as -1, -2, and -3. An overall LH score was calculated using all positive responses and an overall LA score was calculated using all negative responses totaled. Severity of each of these conditions was defined as none (0 points), mild (1-12 points), and moderate-to-severe (>12 points)

Methods cont. STATISTICAL ANALYSES: We used multivariate logistic

regression to examine associations between hypertension, LA, LH, demographic characteristics (age, race, sex, risk factor for HIV transmission), and clinical characteristics (current and nadir CD4+ T cell counts, peak HIV-1 RNA level, current HAART use, smoking, and current illicit drug use)

Final models are adjusted for age, race, sex, current HAART use, current and nadir CD4+ T cell counts

Results347 patients enrolled with a total of 2,278 BP readings (Table 1)Body morphology: no abnormality in 70 (20%) patients

137 (39%) with mild LH and 25 (7%) with moderate LH101 (29%) with mild LA and 14 (4%) with moderate LA

Hypertension-125 patients (35%) had hypertension105 with a clinical diagnosis of hypertension36 with mean SBP >140 mmHg27 with mean DBP >90 mmHg

In adjusted analyses, patients reporting any degree of LA were more than twice as likely to have hypertension compared with patients reporting no abnormalities (OR 2.2; p=0.04), as were patients with any degree of LH (OR 2.5; p=0.01)Additional adjusted analyses were conducted to examine the association with body morphology severity (Table 2)

patients with moderate LH were 4 times as likely to have hypertension (OR 4.3; p<0.01) as patients without abnormalitiespatients with moderate LA were 4 times as likely to have hypertension (OR 4.3; p=0.03) as patients without abnormalitiespatients with mild LH were twice as likely to have hypertension (OR 2.3; p=0.03) as patients without abnormalities patients with mild LA were twice as likely to have hypertension, however this difference was not statistically significantOlder age and higher current CD4+ cell count were also associated with increased risk of hypertension (Table 2)

We hypothesized that the impact of LH on hypertension was mediated, in part, through a higher body mass index (BMI). When BMI was added to the adjusted model, BMI was significantly associated with hypertension (OR=1.1; p<0.001 per kg/m2), and the association between LH and hypertension was no longer present. However, the association between moderate LA and hypertension was present after adjusting for BMI (OR=5.1; p=0.02)

Conclusions We found that LA and LH are significantly associated

with hypertension among patients in routine HIV care Our findings suggest that the association between LH

and hypertension may be mediated via BMI, but that LA is associated with hypertension independent of BMI

There is a dose response effect with more severe body morphology abnormalities associated with greater risk of hypertension

Self-reported measures of LA and LH are associated with clinical outcomes such as hypertension with potential long-term cardiovascular implications

Strengths and limitations The FRAM measure allowed us to examine the

strength of the relationship between hypertension and LA severity separately from LH severity

The observational cross-sectional study design demonstrates a significant association between LA and LH and hypertension but does not provide evidence of causality

Table 1. Clinical and demographic characteristics of study patients (N=347)

No abnormalityN=70

LH N=162

LAN=115

p value

N (%) N (%) N (%)

Sex

Male 61 (87) 136 (84) 102 (89)

Female 9 (13) 26 (16) 13 (11) 0.5

Race

White 48 (69) 111 (69) 89 (77)

Black 14 (20) 41 (25) 18 (16)

Other 8 (11) 10 (6) 8 (7) 0.2

Age (years)

< 30 10 (14) 4 (3) 8 (7)

30-39 21 (30) 52 (32) 18 (16)

40-49 28 (40) 72 (44) 54 (47)

≥ 50 11 (16) 34 (21) 35 (30) 0.001

Risk factor for HIV transmission

MSM 43 (61) 95 (59) 68 (59)

IDU 16 (23) 36 (22) 26 (23)

Heterosexual 11 (16) 30 (19) 17 (15)

Other 0 1 (1) 4 (4) 0.4

Current CD4+ T cell count (cells/mm3)

0-200 16 (23) 23 (14) 33 (29)

201-350 17 (24) 39 (24) 28 (24)

>350 37 (53) 100 (62) 54 (47) 0.045

CD4+ T cell count nadir (cells/mm3)

0-200 39 (56) 110 (68) 83 (72)

201-350 20 (29) 37 (23) 25 (22)

>350 11 (16) 15 (9) 7 (6) 0.1

Body mass index

<18.5 3 (4) 1 (1) 10 (9)

18.5-25.0 36 (51) 52 (32) 59 (51)

25.1-30.0 23 (33) 61 (38) 29 (25)

>30.0 8 (11) 48 (30) 17 (15) <0.001

Cigarette smoking

Never 23 (33) 45 (28) 24 (21)

Current 28 (40) 69 (43) 57 (50)

Past 19 (27) 48(30) 34 (30) 0.4

Currently receiving HAART

Yes 48 (69) 133 (83) 90 (78)

No 22 (31) 27 (17) 25 (22) 0.047

Patients with both LA and LH are placed in the more severe category

Table 2. Adjusted odds ratios for factors associated with development of

hypertension Variable Unadjusted

OR (95% CI; p)Adjusted

OR (95% CI; p)

Body morphology

No abnormality 1 (ref) 1 (ref)

Mild LA 2.4 (1.2-5.0, 0.02) 2.0 (0.92-4.2; 0.08)

Mild LH 2.7 (1.3-5.4, 0.005) 2.3 (1.1-4.7; 0.03)

Moderate LA 5.8 (1.7-19.8, 0.004) 4.3 (1.2-15.6; 0.03)

Moderate LH 5.6 (2.1-15.1, 0.001) 4.3 (1.5-12.4; 0.006)

Age (years)

Less than 30 1 (ref) 1 (ref)

30-40 years 5.9 (0.8-46.7, 0.09) 4.4 (0.5-35.9; 0.2)

40-50 years 13.4 (1.8-102.3, 0.01) 9.4 (1.2-75.2; 0.04)

Over 50 23.2 (3.0-180.9, 0.003) 14.9 (1.8-123.2; 0.01)

CD4+ count* 1.1 (1.0-1.2, 0.01) 1.1 (1.0-1.2; 0.02)

*Modeled per increase of 100 cells/mm3 current CD4+ count