Lipoatrophy and lipohypertrophy are independently associated with hypertension: the effect of lipoatrophy but not lipohypertrophy on hypertension is independent of obesity Heidi M. Crane 1, MD, MPH, Carl Grunfeld 2, MD, PhD, Robert D. Harrington 1, MD, and Mari M. Kitahata 1, MD, MPH From the Departments of Medicine, University of Washington 1, Seattle, WA and University of California 2, 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. Crane 1, MD, MPH, Carl Grunfeld 2, MD, PhD, Robert D. Harrington 1, MD, and Mari M. Kitahata 1, MD, MPH From the Departments of Medicine, University of Washington 1, Seattle, WA and University of California 2, 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 Results  347 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 LH  101 (29%) with mild LA and 14 (4%) with moderate LA  Hypertension-125 patients (35%) had hypertension  105 with a clinical diagnosis of hypertension  36 with mean SBP >140 mmHg  27 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 abnormalities  patients with moderate LA were 4 times as likely to have hypertension (OR 4.3; p=0.03) as patients without abnormalities  patients 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 significant  Older 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/m 2 ), 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 abnormality N=70 LH N=162 LA N=115 p value N (%) Sex Male61 (87)136 (84)102 (89) Female9 (13)26 (16)13 (11)0.5 Race White48 (69)111 (69)89 (77) Black14 (20)41 (25)18 (16) Other8 (11)10 (6)8 (7)0.2 Age (years) < 3010 (14)4 (3)8 (7) (30)52 (32)18 (16) (40)72 (44)54 (47) ≥ 5011 (16)34 (21)35 (30)0.001 Risk factor for HIV transmission MSM43 (61)95 (59)68 (59) IDU16 (23)36 (22)26 (23) Heterosexual11 (16)30 (19)17 (15) Other01 (1)4 (4)0.4 Current CD4+ T cell count (cells/mm 3 ) (23)23 (14)33 (29) (24)39 (24)28 (24) >35037 (53)100 (62)54 (47)0.045 CD4+ T cell count nadir (cells/mm 3 ) (56)110 (68)83 (72) (29)37 (23)25 (22) >35011 (16)15 (9)7 (6)0.1 Body mass index <18.53 (4)1 (1)10 (9) (51)52 (32)59 (51) (33)61 (38)29 (25) >30.08 (11)48 (30)17 (15)<0.001 Cigarette smoking Never23 (33)45 (28)24 (21) Current28 (40)69 (43)57 (50) Past19 (27)48(30)34 (30)0.4 Currently receiving HAART Yes48 (69)133 (83)90 (78) No22 (31)27 (17)25 (22) 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 VariableUnadjusted OR (95% CI; p) Adjusted OR (95% CI; p) Body morphology No abnormality1 (ref) Mild LA2.4 ( , 0.02)2.0 ( ; 0.08) Mild LH2.7 ( , 0.005)2.3 ( ; 0.03) Moderate LA5.8 ( , 0.004)4.3 ( ; 0.03) Moderate LH5.6 ( , 0.001)4.3 ( ; 0.006) Age (years) Less than 301 (ref) years5.9 ( , 0.09)4.4 ( ; 0.2) years13.4 ( , 0.01)9.4 ( ; 0.04) Over ( , 0.003)14.9 ( ; 0.01) CD4+ count*1.1 ( , 0.01)1.1 ( ; 0.02) *Modeled per increase of 100 cells/mm 3 current CD4+ count