High prevalence of hypertension among South Africans starting ART

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There is a high prevalence and incidence of hypertension among HIV-positive people starting antiretroviral therapy (ART) in South Africa, according to research. A fifth of people were hypertensive when they started ART and a further 15% developed hypertension during follow-up.

Traditional risk factors, including age over 40 years and being overweight or obese were predictors of hypertension, as was therapy with some older antiretrovirals. Only a minority of hypertensive people received treatment for their condition.

“Our work adds to the evidence base on hypertension and its risk factors in settings of both high HIV prevalence and the non-HIV risk factors common in middle-income countries,” comment the authors. “Older patients, males, those on nevirapine, zidovudine or stavudine, and those who are overweight/obese should be targeted for frequent blood pressure monitoring and the identification of other cardiovascular risk factors to encourage lifestyle modifications.”

Hypertension is a key risk factor for the development of cardiovascular disease. An estimated 1bn people globally are hypertensive and raised blood pressure is estimated to kill 15m people each year. Prompt diagnosis of hypertension is important as the condition can be controlled through lifestyle modifications (stopping smoking, improvements in diet, weight loss, frequent exercise) and effective medication is also available. The incidence and prevalence of hypertension in low- and middle-income settings, including sub-Saharan Africa, is increasing.

As access to ART is scaled up and deaths from Aids-defining conditions decline, the management of hypertension is emerging as an essential part of HIV care in low- and middle-income countries. Cardiovascular disease is an increasingly important cause of morbidity and mortality among South African ART-treated individuals.

A team of investigators designed a prospective, observational study to determine the prevalence, incidence, predictors and control of hypertension among HIV-positive adults starting ART.

A total of 77,696 people enrolled in the Right to Care Clinical HIV cohort were included in the analysis. All started ART at a publicly funded clinic between 2004 and 2016. ART was based on a non-nucleoside reverse transcriptase inhibitor (NNRTI) and lamivudine plus stavudine, zidovudine, or after 2010, tenofovir.

The primary outcomes were prevalent hypertension at ART initiation and incident hypertension during ART. Prevalent hypertension was defined as a single blood pressure measurement of 140/90 mm/Hg or above in the three months before starting ART, a pre-existing diagnosis of hypertension, or the use of hypertensive drugs.

People with normal blood pressure at baseline were diagnosed with incident hypertension if they met any of the following criteria after ART initiation: at least three blood pressure measurements, at least two days apart above 140/90 mm/Hg (or 130/80 mm/Hg in the presence of co-morbidities); a single blood pressure measurement above 180/110 mm/Hg; documented hypertension in a patient’s note; and documented treatment for hypertension.

Just under two-thirds (61%) of the cohort were female and the median age at ART initiation was 37 years. Median baseline blood pressure was 117/76 mm/Hg. Average BMI was 22.1kg/mm2. A stavudine-containing regimen was started by 48% of people, an equal proportion initiating a combination containing tenofovir.

More than a fifth (22%) of people were hypertensive at baseline. Older people (40 years and older) and individuals classified as overweight or obese were significantly more likely to be hypertensive. Poorer health status, including advanced HIV disease and low haemoglobin, was associated with a lower risk of hypertension.

People with baseline hypertension were excluded from further analysis, leaving a sample of 60,570 people. During follow-up, 13% of these people were diagnosed with hypertension at a median of 13 months after ART initiation. Overall incidence was 5.44 per 100 person-years.

In addition to age, risk factors for incident hypertension included male sex (HR = 1.23; 95% CI, 1.14-1.32) and pre-hypertension (HR = 2.05; 95% CI, 1.92-2.19). People with a baseline CD4 cell count below 50 cells/mm3 were 25% more likely to be diagnosed with incident hypertension compared to those with a CD4 cell count at ART initiation above 350 cells/mm3.

Certain antiretrovirals were also associated with a diagnosis of hypertension. People treated with nevirapine were 27% more likely to develop incident hypertension compared to those who started therapy with efavirenz. People starting stavudine and zidovudine were 40% more likely to develop hypertension than those initiating tenofovir.

A quarter of people with incident hypertension received treatment for elevated blood pressure. More than half (58%) continued to have elevated blood pressure a median of five months after receiving blood pressure medication. A small proportion (2%) developed an illness related to hypertension.

Analysis of the 76% of people who did not receive blood pressure medication showed that 54% still had elevated blood pressure six months after their initial diagnosis of hypertension. A blood pressure-related co-morbidity was reported in approximately 2% of people.

“Over 20% of patients in our cohort had hypertension at ART initiation, and 13% of those with normal blood pressure at ART initiation developed hypertension while on ART,” conclude the authors. “At risk populations should be offered pharmaceutical therapy to help prevent myocardial infarction, heart failure, stroke, and kidney disease. Further research is needed to determine the level of access and adherence to pharmaceutical treatment for hypertension in this population. Additionally, an HIV-negative comparison population is needed to assess the association of the HIV virus itself with hypertension.”

Abstract
Background: One of the key risk factors for cardiovascular disease is hypertension. Hypertension, which leads to heart attacks and strokes, already affects one billion people worldwide, making it a global public health issue. Incidence and prevalence of the condition is on the rise in low- and middle-income countries, with the biggest increase in sub-Saharan Africa and South Africa at the forefront. We examined the prevalence, incidence, predictors, treatment, and control of hypertension among HIV-positive patients on ART in a large South African observational cohort.
Methods: We conducted a prospective study of ART naïve adults initiating ART at a public sector HIV clinic in South Africa between April 2004–2017. Patients with diagnosed hypertension at ART initiation were excluded from the incidence analysis. Log-binomial regression was used to estimate predictors of hypertension at ART initiation, while competing risks regression was used to evaluate the relationship between predictors of incident hypertension, accounting for death as a competing risk.
Results: Among 77,696 eligible patients, 22.0% had prevalent hypertension at ART initiation. Of the remaining patients with no hypertension at ART initiation, 8,125 incident hypertension cases were diagnosed over the period of follow-up, corresponding to an incident rate of 5.4 per 100 person-years (95% confidence interval (CI): 5.3–5.6). We found patients ≥40 years of age and patients with a body mass index (BMI) ≥25kg/m2 were at increased risk of both prevalent and incident hypertension. Male patients and those with pre-hypertension at ART initiation had increased hazards of hypertension over the period of follow-up. When assessing the choice of antiretroviral drug in first-line ART, patients initiated on nevirapine were at 27% increased risk of developing hypertension compared to those initiated on efavirenz, while patients who initiated on either zidovudine or stavudine had a 40% increased risk of developing hypertension compared to patients initiated on tenofovir. Patientswith poorer health status at ART initiation (i.e. WHO III/IV stage, low CD4 count, low hemoglobin levels and low BMI) had a decrease risk of prevalent hypertension. We found an inverse relationship in patients with a CD4 count <50 cells/mm3 at ART initiation who had a 25% increased risk of incident hypertension compared to those with a CD4 count ≥350 cells/mm3.
Conclusion: Over 20% of patients in our cohort had hypertension at ART initiation, and 13% of those with normal blood pressure at ART initiation developed hypertension while on ART. Older patients, males, those on nevirapine, zidovudine or stavudine, and those who are overweight/obese should be targeted for frequent blood pressure monitoring and the identification of other cardiovascular risk factors to encourage lifestyle modifications. Additionally, these groups should be offered pharmaceutical therapy to help prevent myocardial infarction, heart failure, stroke, and kidney disease. Further research is needed to determine the level of access and adherence to pharmaceutical treatment for hypertension in this population. Additionally, an HIV-negative comparison population is needed to assess the association of the HIV virus itself with hypertension.

Authors
Alana T Brennan, Lise Jamieson, Nigel J Crowther, Matthew P Fox, Jaya A George, Kaitlyn M Berry, Andrew Stokes, Mhairi Maskew, Ian Sanne, Lawrence Long, Naseem Cassim, Sydney Rosen

Aidsmap material
PLOS One abstract


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