HIV, Sleep, Nocturnal Non-dipping, and Cardiovascular Disease: a Tanzanian Cohort

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ABSTRACT: The incidence of cardiovascular disease (CVD) in people with HIV (PWH) is ~2.5-fold higher than among HIV-uninfected adults of similar age. HIV-attributable CVD risk is highest in Africa. Ambulatory blood pressure (ABP) monitoring with a portable cuff worn for 24 hours provides mean daytime and nighttime blood pressures and detects abnormalities in the diurnal variation of blood pressure such as nocturnal non-dipping, which is defined by the absence of the 10% usual fall (dip) in blood pressure at night. ABP more accurately predicts CVD events than office blood pressure. Elevated nighttime blood pressure and non-dipping may contribute to the excess CVD risk in PWH. Small, cross-sectional studies suggest that non- dipping is more common in PWH and may be associated with CVD. The long-term goal is to reduce CVD morbidity and mortality in PWH. The study objectives are to 1) compare the time course of non-dipping and resulting preclinical CVD in PWH vs. HIV-uninfected adults and 2) to identify potential pathophysiologic pathways that could be targets for future intervention. We propose a comparative cohort study of PWH and HIV-uninfected adults with repeated measures of ABP, sleep, SNS activity and preclinical CVD to be conducted in an established cohort of 500 PWH and 500 HIV-uninfected adults in Tanzania. Aim 1: To determine the prevalence of confirmed non-dipping and its association with incident preclinical CVD after 36 months in a cohort of 500 PWH on stable ART and 500 matched HIV-uninfected adults (age >30 years) in Tanzania. ABP will be performed at baseline and then repeated at 1 month. Preclinical CVD will be quantified at baseline and after 18 and 36 months. Incidence of CVD events will also be monitored. We will also examine other ABP abnormalities in relationship to preclinical CVD. Aim 2: To determine the temporal relationship between sleep disorders, SNS activity and non-dipping and whether this differs by HIV status or gender. We will quantify sleep and SNS activity at baseline and after 18 and 36 months on all participants. We will also investigate the renin-angiotensin system, insulin resistance and chronic inflammation as potential pathways leading to non-dipping. We will also compare temporal trends in sleep and SNS activity between PWH and HIV-uninfected adults. The proposed research will be the first longitudinal study of ABP and sleep disorders in Africa and will directly inform HIV-specific and general guidelines. We will also lay groundwork for a mechanistic clinical trial to test a novel, low-cost strategy targeting ABP abnormalities to prevent CVD in PWH.