Correlates of prevalent hypertension in a large cohort of HIV-infected women: Women's Interagency HIV Study

Correlates of hypertension were assessed in 1266 HIV-positive and 368 HIV-negative women in the Women's Interagency HIV Study. Hypertension prevalence was similar in HIV-positive and HIV-negative women (26 versus 28%, P = 0.38). Factors associated with hypertension included increasing age (P < 0.0001), African-American race (P < 0.0001), and body mass index greater than 30 kg/m² (P < 0.0001), whereas current pregnancy was protective (P < 0.04). HIV infection, CD4 cell count, HIV-1 viral load, and antiretroviral therapy were not associated with hypertension.

Hypertension has become a potentially significant cause of morbidity in HIV-infected individuals, as a result of the prolongation in survival with the use of HAART ^[1]. Hypertension is increased in individuals with diabetes, central obesity, or dyslipidemia, all of which may occur among HIV-infected patients treated with HAART.

We evaluated the prevalence and correlates of hypertension among HIV-infected participants in the Women's Interagency HIV Study (WIHS).

A total of 2059 HIV-positive and 569 demographically similar HIV-negative women were enrolled between 1994 and 1995. Study visits at 6-month intervals include an extensive interview (including self-reported medication use), physical examination, and blood tests. At visit 13 (approximate year 6.5), a standardized blood pressure protocol was initiated. Blood pressure was measured after sitting for at least 5 min and at least 30 min after the intake of nicotine or caffeine; the first blood pressure reading was averaged with a second reading after 15 s of elevation of the arm over the head. This analysis included data from visits 13-16.

At each study visit, hypertension was defined as having at least one of the following: diastolic blood pressure 90 mmHg or greater, systolic blood pressure 140 mmHg or greater, or current receipt of antihypertensive medication(s).

At each visit, HAART use was defined as: (i) two or more nucleoside reverse transcriptase inhibitors (NRTI) with at least one protease inhibitor (PI) or one non-nucleoside reverse transcriptase inhibitor (NNRTI); (ii) one NRTI with at least one PI and one NNRTI; (iii) ritonavir and saquinavir with one NRTI and no NNRTI; or (iv) abacavir with three or more NRTI in the absence of PI or NNRTI. Monotherapy was one NRTI, only PI, or only NNRTI. Combination therapy included all other regimens.

Hypertension data were available on 1266 HIV-positive and 368 HIV-negative women over 5603 visits (4358 visits in HIV-positive, 1245 visits in HIV-negative). The 6-month visit interval was used as the follow-up unit. We used logistic regression with generalized estimating equations to determine factors related to prevalent hypertension over follow-up ^[2]. Factors associated with hypertension in univariate analyses were included in multivariate models. Independent variables included HIV status, age, race, education, body mass index (BMI), current smoking, current pregnancy, and injection drug use within 6 months. HIV status, race, and education were modeled as fixed covariates; other variables were modeled as time-dependent covariates. Among HIV-positive women, CD4 lymphocyte count, HIV-1 viral load, and antiretroviral therapy (ART)were evaluated as time-dependent covariates. ART was evaluated as: (i) classes (NRTI, NNRTI, PI); (ii) regimens (no antiretroviral medication, monotherapy, combination therapy, HAART based on PI, HAART based on NNRTI, other HAART); (iii) duration of HAART.

Average follow-up was 1.3 years; HIV-positive women contributed 1643 person-years and HIV-negative women contributed 452.7 person-years of follow-up. HIV-positive women were older than HIV-negative women (median age 36.3 years versus 35 years, P < 0.0008), and had lower median BMI (26 versus 30 kg/m², P < 0.0001). The groups did not differ with regard to ethnicity, current pregnancy, current smoking, and injection drug use within 6 months or education.

Hypertension prevalence was similar between the HIV-positive and HIV-negative women at the baseline WIHS visit, before the development of a standardized blood pressure measurement (19 versus 20%, P = 0.69) and at visit 13 with the standardized blood pressure protocol (18 versus 20%, P = 0.11).

In multivariate analyses among all WIHS participants, increasing age, African-American race and BMI greater than 30 kg/m² were positively associated with prevalent hypertension, whereas current pregnancy was inversely related (Table 1). These associations were not different in HIV-positive compared with HIV-negative women (all P > 0.05). HIV infection was not associated with hypertension (P = 0.68). Among HIV-infected women, CD4 cell count and HIV-1 viral load were not associated with hypertension. Neither individual classes of ART, specific HAART regimen, nor the duration of HAART were associated with prevalent hypertension.

Table 1

The prevalence of hypertension was similar in HIV-infected and uninfected women, consistent with some previous reports ^[3,4]. In other studies documenting a higher prevalence of hypertension among HIV-infected participants, metabolic and demographic factors, as opposed to HIV parameters, were associated with hypertension ^[5,6].

Previous reports demonstrated elevated hypertension prevalence in HIV-infected individuals initiating HAART ^[6-8] or increases in blood pressure in individuals treated with HAART over prolonged periods ^[9]. The role of HAART in the pathogenesis of hypertension is not well understood. HAART is, however, linked to a series of metabolic abnormalities associated with hypertension, including insulin resistance, diabetes, and elevated cholesterol and triglyceride levels. In some studies reporting elevated hypertension with HAART, multivariate analyses demonstrated that metabolic abnormalities, and not HAART per se, were correlated with hypertension ^[3-6,10]. Similar to the WIHS, the D:A:D cohort study failed to demonstrate a relationship between HAART, or any class of ART, and the prevalence or incidence of hypertension, whereas higher age and BMI were correlated with hypertension ^[10]. The bulk of evidence thus suggests that neither HIV nor ART per se are directly linked to hypertension. Rather, traditional factors such as age, African-American race, and obesity are primarily involved.

A major strength of the current study is the use of data from a large, prospective cohort study. Whereas blood pressure measurements were accomplished across clinical sites by diverse examiners, a blood pressure protocol served to enhance reproducibility across sites and over time. Our methods of ascertaining medication usage have been employed consistently among all sites; self-reported medication use has been validated in previous WIHS studies ^[11]. Our data are limited by the fact that we did not use full follow-up data, because we began our standardized blood pressure protocol only at visit 13.

In summary, we have shown, in a large cohort of HIV-infected women that ART is not associated with the presence of hypertension. Similar to HIV-negative women, standard risk factors for hypertension predominate in HIV-infected women. Further assessment of these patients over time will be required to ascertain the full consequences and correlates of hypertension among HIV-infected women.

Acknowledgements

Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (principal investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Phyllis Tien); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange).

Sponsorship: The WIHS is funded by the National Institute of Allergy and Infectious Diseases, with supplemental funding from the National Cancer Institute, the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, and the National Institute of Craniofacial and Dental Research, U01-AI-35004, U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-HD-32632, U01-AI-34993, U01-AI-42590, M01-RR00079 and M01-RR00083.