Sex modifies the association between HIV and coronary artery disease among older adults in Uganda.

INTRODUCTION: Little is known about the epidemiology of coronary artery disease (CAD) in sub-Saharan Africa, where the majority of people living with HIV (PLHIV) live. We assessed the association of HIV with CAD and explored relationships with monocyte activation in sex-stratified analyses of older PLHIV and people without HIV (PWOH) in Uganda. METHODS: The Ugandan Study of HIV effects on the Myocardium and Atherosclerosis (mUTIMA) follows 100 PLHIV on antiretroviral therapy (ART) and 100 age- and sex-matched PWOH controls in Kampala, Uganda; all >45 years of age with >1 cardiovascular disease risk factor. At the year 2 exam (2017-2019), 189 participants had available coronary calcium score and 165 had coronary CT angiography (CCTA) for this analysis. A subset of participants (n = 107) had both CCTA and fresh whole blood flow cytometry for monocyte phenotyping. RESULTS: Median age was 57.8 years and 63% were females. Overall, 88% had hypertension, 37% had diabetes and 4% were smokers. Atherosclerotic cardiovascular disease (ASCVD) risk was modestly higher for PWOH, but not statistically significant (median 10-year ASCVD risk 7.2% for PLHIV vs. 8.6% for PWOH, p = 0.09). Median duration of ART was 12.7 years and 86% had suppressed viral load. Despite a high prevalence of risk factors, only 34/165 (21%, 95% CI 15-28%) had any coronary plaque. After adjustment for ASCVD risk score, HIV status was not associated with CAD (OR 0.55, 95% CI 0.23-1.30) but was associated with more severe CAD (segment severity score>3) among those with disease (OR 10.9, 95% CI 1.67-70.45). Females had a trend towards higher odds of CAD among PLHIV (OR 4.1, 95% CI 0.4-44.9), but a trend towards lower odds of CAD among PWOH (OR 0.30; 95% CI 0.07-1.3; HIV*sex interaction p = 0.019). CAD was positively correlated with classical monocytes (r = 0.3, p = 0.012) and negatively correlated with CX3CR1 expression (r = -0.31, p = 0.011) in PLHIV and negatively correlated with patrolling monocytes (r = -0.36, p = 0.031) and tissue factor expression (r = -0.39, p = 0.017) in PWOH. CONCLUSIONS: Our results suggest that HIV may be associated more with severity rather than the presence of CAD in Uganda. Sex differences in the HIV effect suggest that tailored CAD prevention strategies may be required in this setting.

Assessing Cardiovascular Risk in People Living with HIV: Current Tools and Limitations.

PURPOSE OF REVIEW: To provide the current state of the development and application of cardiovascular disease (CVD) prediction tools in people living with HIV (PLWH). RECENT FINDINGS: Several risk prediction models developed on the general population are available to predict CVD risk, the most notable being the US-based pooled cohort equations (PCE), the Framingham risk functions, and the Europe-based SCORE (Systematic COronary Risk Evaluation). In validation studies in cohorts of PLWH, these models generally underestimate CVD risk, especially in individuals who are younger, women, Black race, or predicted to be at low/intermediate risk. An HIV-specific CVD prediction model, the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, is available, but its performance is modest, especially in US-based cohorts. Enhancing CVD prediction with novel biomarkers of inflammation or coronary artery calcification is of interest but has not yet been evaluated in PLWH. Finally, studies on CVD risk prediction are lacking in diverse PLWH globally. While available risk models for CVD prediction in PLWH remain suboptimal, clinicians should remain vigilant of higher CVD risk in this population and should use any of these risk scores for risk stratification to guide preventive interventions. Focus on established traditional risk factors such as smoking remains critical in PLWH. Risk prediction functions tailored to PLWH in diverse settings will enhance clinicians' ability to deliver optimal preventive care.

Measures of Adipose Tissue Redistribution and Atherosclerotic Coronary Plaque in HIV.

OBJECTIVE: People with HIV (PWH) who are well treated on antiretroviral therapy remain at increased risk for body composition changes, including increased visceral adipose tissue (VAT) and reduced subcutaneous adipose tissue (SAT), as well as increased cardiovascular disease (CVD). The relationship between adipose compartments and coronary disease is not well understood among PWH. METHODS: A total of 148 PWH and 68 uninfected individuals without CVD were well phenotyped for VAT and SAT via single-section abdominal computed tomography (CT) at L4. Coronary artery calcium (CAC) score was assessed by noncontrast cardiac CT and coronary plaque composition by coronary CT angiography. RESULTS: Increased VAT was significantly related to increased presence of plaque (OR, 1.55 per 100 cm2 ; P = 0.008) and CAC > 0 (OR, 1.56 per 100 cm2 ; P = 0.006) in the HIV group. In contrast, increased SAT was related to reduced presence of plaque (OR, 0.79 per 100 cm2 ; P = 0.057) and reduced CAC > 0 (OR, 0.69 per 100 cm2 , P = 0.007) among PWH. The VAT to SAT ratio showed a strong relationship to overall presence of calcified plaque (OR, 3.30; P = 0.03) and CAC > 0 (OR, 3.57; P < 0.001) in the HIV group. VAT and waist to hip ratio, but not SAT, were strong predictors of plaque in the uninfected group. BMI did not relate in either group. CONCLUSIONS: Fat redistribution phenotyping by simultaneous quantification of VAT and SAT as independent measures could help identify those PWH at higher risk for CVD.

Low Awareness of and Access to Pre-exposure Prophylaxis But High Interest Among Heterosexual Women in Cleveland, Ohio.

Women received <5% of all US pre-exposure prophylaxis (PrEP) prescriptions in 2016. Among 351 heterosexual women surveyed in Cleveland, Ohio, 14.5% were aware of PrEP, 20.5% knew where to access PrEP, 75.9% were willing to try PrEP, and 50.9% expressed interest in more information.

Serum Lipocalin 2 (Neutrophil Gelatinase-Associated Lipocalin) in Relation to Biomarkers of Inflammation and Cardiac Stretch During Activation of the Renin-Angiotensin-Aldosterone System in Human Immunodeficiency Virus.

PURPOSE: To evaluate the relationship of lipocalin 2 to inflammation and cardiac injury with increased aldosterone in human immunodeficiency virus (HIV). METHODS: A standardized 6-day low-sodium diet was used to stimulate renin-angiotensin-aldosterone system (RAAS) activation, and serum lipocalin 2 and biomarkers of inflammation and cardiac stretch were assessed among persons with or without HIV. RESULTS: Lipocalin 2 levels increased with RAAS activation compared with suppression in the HIV group (median level [interquartile range], 71.3 [59.2-99.7] vs 67.0 [51.8-86.3] ng/mL; P = .01). During RAAS activation, lipocalin 2 was related to biomarkers of inflammation (tumor necrosis factor α [P = .007]), monocyte/macrophage activation (soluble CD163 [P = .005] and chemokine [C-C motif] ligand 2 [P = .03]), and markers of cardiac stretch (brain natriuretic peptide [P < .001] and N-terminal fragment of the prohormone brain natriuretic peptide [P = .001]) in HIV. CONCLUSION: Lipocalin 2 may be important in modulating aldosterone-induced inflammation, monocyte activation, and cardiac stretch during RAAS activation in HIV. CLINICAL TRIAL REGISTRATION: NCT01407237.

Stroke in HIV.

Stroke is a heterogeneous disease in persons living with human immunodeficiency virus (HIV). HIV is thought to increase the risk of stroke through both HIV-related and traditional stroke risk factors, which vary with respect to the patient's age and clinical characteristics. Numerous studies show that detectable viremia and immunosuppression increase the risk of stroke across all ages, whereas traditional risk factors are more common in the aging population with HIV. As persons living with HIV age and acquire traditional stroke risk factors, the prevalence of stroke will likely continue to increase. Large- and small-vessel disease are the most common causes of stroke, although it is important to evaluate for infectious etiology as well. Research regarding the management of stroke in patients with HIV is scant, and recommendations often parallel those for the general population. Treatment of HIV and effective reduction of traditional stroke risk factors is important to reduce the risk of stroke in persons living with HIV. Future research will help elucidate the pathophysiology of HIV and stroke risk, investigate sex differences in stroke risk, and evaluate the safety and benefits of standard stroke preventative measures and HIV-specific interventions in this population.

Cardiovascular Complications of HIV in Endemic Countries.

Effective combination antiretroviral therapy (ART) has enabled human immunodeficiency virus (HIV) infection to evolve from a generally fatal condition to a manageable chronic disease. This transition began two decades ago in high-income countries and has more recently begun in lower income, HIV endemic countries (HIV-ECs). With this transition, there has been a concurrent shift in clinical and public health burden from AIDS-related complications and opportunistic infections to those associated with well-controlled HIV disease, including cardiovascular disease (CVD). In the current treatment era, traditional CVD risk factors and HIV-related factors both contribute to an elevated risk of myocardial infarction, stroke, heart failure, and arrhythmias. In HIV-ECs, the high prevalence of persons living with HIV and growing prevalence of CVD risk factors will contribute to a growing epidemic of HIV-associated CVD. In this review, we discuss the epidemiology and pathophysiology of cardiovascular complications of HIV and the resultant implications for public health efforts in HIV-ECs.

Toys and gadgets: construct validity of apathy in Parkinson's disease.

Apathy is one of the primary neuropsychiatric signatures in Parkinson's disease, yet little research has addressed the construct validity of two commonly used apathy measures, the Apathy Scale and the Lille Apathy Rating Scale. The authors tested the hypothesis that apathy is associated with reduced initiative/engaged behaviors on a laboratory-based measure of apathy. Support was found for the hypothesis that apathy, as indexed by the Apathy Scale and the Lille Apathy Rating Scale, is associated with reduced initiative/engagement on an experimental measure of apathy in Parkinson's disease patients. These findings provide independent evidence for the construct validity of self-report apathy scales, beyond clinician judgment.