Evolving mechanisms and presentations of cardiovascular disease in people with HIV: implications for management.

People with HIV (PWH) are at elevated risk for cardiovascular diseases (CVDs), including myocardial infarction, heart failure, and sudden cardiac death, among other CVD manifestations. Chronic immune dysregulation resulting in persistent inflammation is common among PWH, particularly those with sustained viremia and impaired CD4+ T cell recovery. This inflammatory milieu is a major contributor to CVDs among PWH, in concert with common comorbidities (such as dyslipidemia and smoking) and, to a lesser extent, off-target effects of antiretroviral therapy. In this review, we discuss the clinical and mechanistic evidence surrounding heightened CVD risks among PWH, implications for specific CVD manifestations, and practical guidance for management in the setting of evolving data.

Myocardial strain is associated with adverse cardiac events in patients treated with chimeric antigen receptor (CAR) T-cell therapy.

BACKGROUND: Cardiovascular events, including heart failure and arrhythmias, following chimeric antigen receptor (CAR) T-cell therapy are increasingly recognized. Although global longitudinal strain (GLS) has demonstrated prognostic utility for other cancer therapy-related cardiac dysfunction, less is known regarding the association of GLS with adverse cardiac events following CAR T-cell therapy. OBJECTIVES: To determine the association of baseline GLS with adverse cardiovascular events in adults receiving CAR-T cell therapy. METHODS: Patients who had an echocardiogram within 6 months prior to receiving CAR T-cell therapy were retrospectively identified. Clinical data and cardiac events were collected via chart review. Echocardiograms were analyzed offline for GLS, left ventricular ejection fraction, and Doppler parameters. Multivariable logistic regression was used to determine the association between adverse cardiovascular events and echocardiographic parameters. RESULTS: Among 75 CAR T-cell therapy patients (mean age 63.9, 34.7% female), nine patients (12%) experienced cardiac events (CEs) including cardiovascular death, new/worsening heart failure, and new/worsening arrhythmia within 1 year of treatment. In univariable models, higher baseline GLS (OR 0.78 [0.63, 0.96], p = .021) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.40 [1.08, 1.81], p = .012) was associated with a higher risk of CE. After adjusting for age and LDH, higher baseline GLS (OR 0.65 [0.48-0.88], p = <.01) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.56 [1.06, 2.29], p = .024) was associated with a higher risk of CE. CONCLUSION: Lower GLS and higher mitral E/e' on a baseline echocardiogram were associated with higher risk for CEs in patients receiving CAR T-cell therapy.

Single-cell profiling reveals inflammatory polarization of human carotid versus femoral plaque leukocytes.

Femoral atherosclerotic plaques are less inflammatory than carotid plaques histologically, but limited cell-level data exist regarding comparative immune landscapes and polarization at these sites. We investigated intraplaque leukocyte phenotypes and transcriptional polarization in 49 patients undergoing femoral (n = 23) or carotid (n = 26) endarterectomy using single-cell RNA-Seq (scRNA-Seq; n = 13), flow cytometry (n = 24), and IHC (n = 12). Comparative scRNA-Seq of CD45+-selected leukocytes from femoral (n = 9; 35,265 cells) and carotid (n = 4; 30,655 cells) plaque revealed distinct transcriptional profiles. Inflammatory foam cell-like macrophages and monocytes comprised higher proportions of myeloid cells in carotid plaques, whereas noninflammatory foam cell-like macrophages and LYVE1-overexpressing macrophages comprised higher proportions of myeloid cells in femoral plaque (P < 0.001 for all). A significant comparative excess of CCR2+ macrophages in carotid versus plaque was observed by flow cytometry in a separate validation cohort. B cells were more prevalent and exhibited a comparatively antiinflammatory profile in femoral plaque, whereas cytotoxic CD8+ T cells were more prevalent in carotid plaque. In conclusion, human femoral plaques exhibit distinct macrophage phenotypic and transcriptional profiles as well as diminished CD8+ T cell populations compared with human carotid plaques.

Associations between alcohol and cigarette use and type 1 and 2 myocardial infarction among people with HIV.

OBJECTIVES: People with HIV have a higher risk of myocardial infarction (MI) than the general population, with a greater proportion of type 2 MI (T2MI) due to oxygen demand-supply mismatch compared with type 1 (T1MI) resulting from atherothrombotic plaque disruption. People living with HIV report a greater prevalence of cigarette and alcohol use than do the general population. Alcohol use and smoking as risk factors for MI by type are not well studied among people living with HIV. We examined longitudinal associations between smoking and alcohol use patterns and MI by type among people living with HIV. DESIGN AND METHODS: Using longitudinal data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort, we conducted time-updated Cox proportional hazards models to determine the impact of smoking and alcohol consumption on adjudicated T1MI and T2MI. RESULTS: Among 13 506 people living with HIV, with a median 4 years of follow-up, we observed 177 T1MI and 141 T2MI. Current smoking was associated with a 60% increase in risk of both T1MI and T2MI. In addition, every cigarette smoked per day was associated with a 4% increase in risk of T1MI, with a suggestive, but not significant, 2% increase for T2MI. Cigarette use had a greater impact on T1MI for men than for women and on T2MI for women than for men. Increasing alcohol use was associated with a lower risk of T1MI but not T2MI. Frequency of heavy episodic alcohol use was not associated with MI. CONCLUSIONS: Our findings reinforce the prioritization of smoking reduction, even without cessation, and cessation among people living with HIV for MI prevention and highlight the different impacts on MI type by gender.

Chronic obstructive pulmonary disease and the risk for myocardial infarction by type in people with HIV.

OBJECTIVES: The relationship between chronic obstructive pulmonary disease (COPD) and cardiovascular disease in people with HIV (PWH) is incompletely understood. We determined whether COPD is associated with risk of myocardial infarction (MI) among PWH, and if this differs for type 1 (T1MI) and type 2 (T2MI). DESIGN: We utilized data from five sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, a multisite observational study. METHODS: Our primary outcome was an adjudicated MI, classified as T1MI or T2MI. We defined COPD based on a validated algorithm requiring COPD diagnosis codes and at least 90-day continuous supply of inhalers. We conducted time-to-event analyses to first MI and used multivariable Cox proportional hazards models to measure associations between COPD and MI. RESULTS: Among 12 046 PWH, 945 had COPD. Overall, 309 PWH had an MI: 58% had T1MI ( N  = 178) and 42% T2MI ( N  = 131). In adjusted models, COPD was associated with a significantly increased risk of all MI [adjusted hazard ratio (aHR) 2.68 (95% confidence interval (CI) 1.99-3.60)] even after including self-reported smoking [aHR 2.40 (95% CI 1.76-3.26)]. COPD was also associated with significantly increased risk of T1MI and T2MI individually, and with sepsis and non-sepsis causes of T2MI. Associations were generally minimally changed adjusting for substance use. CONCLUSION: COPD is associated with a substantially increased risk for MI, including both T1MI and T2MI, among PWH. Given the association with both T1MI and T2MI, diverse mechanistic pathways are involved. Future strategies to decrease risk of T1MI and T2MI in PWH who have COPD are needed.

Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among Trypanosoma cruzi Seropositive Individuals in Brazil.

Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.

Ideal Cardiovascular Health: Distribution, Determinants and Relationship with Health Status among People Living with HIV in Urban Tanzania.

Background: Ageing adults living with HIV (ALHIV) have increased risk of cardiovascular diseases as a result of HIV-infection-related chronic immune activation and inflammatory responses. Cardiovascular health index (CVHI) is a valid and relatively simple index for assessing the cardiovascular health (CVH) of the general population. Use of this index among ALHIV in Sub Saharan Africa, a resource-restricted setting where it could be mostly beneficial, remains limited. Understanding of the distribution and associated factors may inform the design of optimal interventions to improve CVH of ALHIV. Objective: We aimed to assess the distribution and factors associated with CVHI scores among ALHIV in an urban setting in Tanzania. Methods: A cross-sectional study was conducted among ALHIV on antiretroviral therapy at six HIV clinics in Dar-es-Salaam, Tanzania. We summed the score of each of the seven CVHI metric to obtain the overall CVHI score and assessed the distribution of the score by sex. We then categorized the overall score into ideal (5-7), intermediate (3-4) and poor (<3) CVH categories and performed ordinal regression to identify CVHI score associated factors. Results: In all, 629 ALHIV [mean age of 43.5(SD ± 11.2) years] were enrolled. Most had ideal levels of blood glucose (96.2%) and smoking status (83.4%) while less than half had ideal BMI (48.1%), blood pressure (BP) (43.9%) and dietary intake (7.8%). Less than half (47.6%) showed ideal CVH, while less than 1% had all seven metrics at ideal level. Older age (0.96(95%CI:0.95-0.97), p-value < 0.001), being retired/unemployed (0.59(95%CI:0.43-0.81), p-value < 0.01), being employed (0.76(95%CI:0.62-0.94), p-value = 0.01) alcohol use (0.41(95%CI:0.21-0.80), p-value = 0.01) and presence of non-communicable disease comorbidities (0.68(95%CI:0.48-0.97), p-value = 0.04) had significant lower odds of ideal CVH. Conclusion: Based on our findings, interventions to improve CVH of ALHIV should target BP management, health education on diet for BMI control and reduction in alcohol consumption, particularly among ageing ALHIV with comorbidities.

Adverse Cardiac Effects of CAR T-Cell Therapy: Characteristics, Surveillance, Management, and Future Research Directions.

This review summarizes the current literature on the adverse cardiac effects of CAR T-cell therapy. Case reports and series suggest that major adverse cardiovascular events are not uncommon after CAR T-cell therapy; however, limited data exist regarding incidence, pathophysiology, and prevention strategies related to CAR T-associated cardiovascular events. As cellular therapy advances and the indications for its use continue to expand, it is essential to better understand its associated cardiovascular toxicities. Biomarkers, cardiac imaging, longitudinal data from larger populations, and translational research are all essential areas for further research. Interestingly, CAR T-cell therapy can also be used to reverse cardiac fibrosis in murine models. Altogether this underscores the need to broadly understand how T-cells, endogenous and engineered, may impact cardiovascular diseases.

Brief Report: Insomnia and Risk of Myocardial Infarction Among People With HIV.

BACKGROUND: Insomnia is common among people with HIV (PWH) and may be associated with increased risk of myocardial infarction (MI). This study examines the association between insomnia and MI by MI type among PWH. SETTING: Longitudinal cohort study of PWH at 5 Centers for AIDS Research Network of Integrated Clinical Systems sites. METHODS: Clinical data and patient-reported measures and outcomes from PWH in care between 2005 and 2018 were used in this study. Insomnia, measured at baseline, was defined as having difficulty falling or staying asleep with bothersome symptoms. The Centers for AIDS Research Network of Integrated Clinical Systems centrally adjudicates MIs using expert reviewers, with distinction between type 1 MI (T1MI) and type 2 MI (T2MI). Associations between insomnia and first incident MI by MI type were measured using separate Cox proportional hazard models adjusted for age, sex, race/ethnicity, traditional cardiovascular disease risk factors (hypertension, dyslipidemia, poor kidney function, diabetes, and smoking), HIV markers (antiretroviral therapy, viral suppression, and CD4 cell count), and stimulant use (cocaine/crack and methamphetamine). RESULTS: Among 12,448 PWH, 48% reported insomnia. Over a median of 4.4 years of follow-up, 158 T1MIs and 109 T2MIs were identified; approximately half of T2MIs were attributed to sepsis or stimulant use. After adjustment for potential confounders, we found no association between insomnia and T1MI (hazard ratio = 1.05, 95% confidence interval: 0.76 to 1.45) and a 65% increased risk of T2MI among PWH reporting insomnia compared with PWH without insomnia (hazard ratio = 1.65, 95% confidence interval: 1.11 to 2.45). CONCLUSIONS: PWH reporting insomnia are at an increased risk of T2MI, but not T1MI, compared with PWH without insomnia, highlighting the importance of distinguishing MI types among PWH.

HIV and Cardiovascular Disease: From Insights to Interventions.

Individuals with HIV have elevated risks for cardiovascular diseases (CVDs) ranging from myocardial infarction to heart failure. Our understanding of this heightened HIV-associated cardiovascular risk has evolved over the past 2 decades. In the early era of antiretroviral therapy (ART), concern existed that ART was the primary driver of cardiovascular risk. However, it has become increasingly apparent that HIV-related viremia, immune dysregulation, and inflammation are primary drivers of HIV-associated cardiovascular risk, along with traditional cardiovascular risk factors such as tobacco smoking. Indeed, early and effective ART blunts risk for CVDs among individuals with HIV. Despite these improvements in HIV-associated cardiovascular risk, questions remain regarding how to optimally predict, prevent, and treat CVDs among individuals with HIV. Efforts are underway to define more precisely which diagnostic and therapeutic strategies will be most effective in curbing HIV-associated CVDs.

Hypoxia-inducible factors individually facilitate inflammatory myeloid metabolism and inefficient cardiac repair.

Hypoxia-inducible factors (HIFs) are activated in parenchymal cells in response to low oxygen and as such have been proposed as therapeutic targets during hypoxic insult, including myocardial infarction (MI). HIFs are also activated within macrophages, which orchestrate the tissue repair response. Although isoform-specific therapeutics are in development for cardiac ischemic injury, surprisingly, the unique role of myeloid HIFs, and particularly HIF-2α, is unknown. Using a murine model of myocardial infarction and mice with conditional genetic loss and gain of function, we uncovered unique proinflammatory roles for myeloid cell expression of HIF-1α and HIF-2α during MI. We found that HIF-2α suppressed anti-inflammatory macrophage mitochondrial metabolism, while HIF-1α promoted cleavage of cardioprotective MerTK through glycolytic reprogramming of macrophages. Unexpectedly, combinatorial loss of both myeloid HIF-1α and HIF-2α was catastrophic and led to macrophage necroptosis, impaired fibrogenesis, and cardiac rupture. These findings support a strategy for selective inhibition of macrophage HIF isoforms and promotion of anti-inflammatory mitochondrial metabolism during ischemic tissue repair.

Associations Between HIV Serostatus and Cardiac Structure and Function Evaluated by 2-Dimensional Echocardiography in the Multicenter AIDS Cohort Study.

Background We aimed to investigate whether there are differences in cardiac structure and systolic and diastolic function evaluated by 2-dimensional echocardiography among men living with versus without HIV in the era of combination antiretroviral therapy. Methods and Results We performed a cross-sectional analysis of 1195 men from MACS (Multicenter AIDS Cohort Study) who completed a transthoracic echocardiogram examination between 2017 and 2019. Associations between HIV serostatus and echocardiographic indices were assessed by multivariable regression analyses, adjusting for demographics and cardiovascular risk factors. Among men who are HIV+, associations between HIV disease severity markers and echocardiographic parameters were also investigated. Average age was 57.1±11.9 years; 29% of the participants were Black, and 55% were HIV+. Most men who were HIV+ (77%) were virally suppressed; 92% received combination antiretroviral therapy. Prevalent left ventricular (LV) systolic dysfunction (ejection fraction <50%) was low and HIV serostatus was not associated with left ventricular ejection fraction. Multivariable adjustment models showed that men who were HIV+ versus those who were HIV- had greater LV mass index and larger left atrial diameter and right ventricular (RV) end-diastolic area; lower RV function; and higher prevalence of diastolic dysfunction. Higher current CD4+ T cell count ≥400 cell/mm3 versus <400 was associated with smaller LV diastolic volume and RV area. Virally suppressed men who were HIV+ versus those who were HIV- had higher indexed LV mass and left atrial areas and greater diastolic dysfunction. Conclusions HIV seropositivity was independently associated with greater LV mass index, left atrial and RV sizes, lower RV function and diastolic abnormalities, but not left ventricular ejection fraction, which may herald a future predisposition to heart failure with preserved ejection fraction among men living with HIV.

Lipoprotein(a) and High Sensitivity C-Reactive Protein among Patients with HIV in Ghana: The Study on Cardiovascular Risk Profile of HIV-Infected Patients on HAART (SCRIPT).

Background: Lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (hs-CRP) levels are associated with cardiovascular disease (CVD) in the general population, even after adjusting for conventional CVD risk factors. However, data are limited regarding the distribution of Lp(a) and hs-CRP among patients with HIV in Ghana. We explored levels of Lp(a), hs-CRP and other cardiovascular risk factors among people who were HIV positive (HIV+) on ART (HIV+ART+), HIV+ART-, and HIV-ART- in a Ghanaian population. Methods: We conducted a cross sectional study, recruited individuals who were HIV+ART+ and HIV+ART- from the largest HIV clinic in central Ghana between August 2018 and December 2019. HIV negative controls were recruited from communities and adjoining suburbs of Kumasi. Lipoprotein(a) was measured using Immunoturbidimetric assay and high sensitive-CRP concentrations were determined using particle-enhanced turbidimetric assay. We compared levels of Lp(a), hs-CRP, and conventional CVD risk factors among these groups and used multivariable stepwise logistic regression models to explore associations between them. Results: Among HIV+ART+ (n = 156), HIV+ART- (n = 131), and HIV-ART- (n = 147), mean(SD) ages were 48 (9.1) years, 41 (11.1) years and 45 (11.9) years, p = <0.001, proportion of females were 71.2%, 67.9% and 73.5% respectively. Median(IQR) concentrations of hs-CRP in mg/L were 1.7 (0.8,4.5), 2.03 (0.5,8.58) and 1.0 (0.45,2.74) across respective groups and the proportion of elevated Lp(a) concentrations (Lp[a] > 30mg/dL) were 70%, 48% and 62% among HIV+ART+,HIV+ART- and HIV-ART- participants respectively. Diabetes mellitus, dyslipidemia, waist-to-hip ratio and metabolic syndrome were associated with higher hs-CRP levels. Compared to HIV-ART-, HIV+ patients had higher odds of having hs-CRP > 3mg/L while HIV+ART+ patients had higher odds of elevated Lp(a) than HIV+ART- after multivariable adjustment. Conclusion: PLWHA in Ghana are associated with higher odds of elevated hs-CRP, regardless of ART use. HIV+ART+ is significantly associated with higher odds of elevated Lp(a) levels compared to HIV+ART-; even after multivariable adjustments. Reasons for this and potential clinical implications merit further study.

HIV and cardiovascular disease.

HIV-related cardiovascular disease research is predominantly from Europe and North America. Of the estimated 37·9 million people living with HIV worldwide, 25·6 million live in sub-Saharan Africa. Although mechanisms for HIV-related cardiovascular disease might be the same in all people with HIV, the distribution of cardiovascular disease risk factors varies by geographical location. Sub-Saharan Africa has a younger population, higher prevalence of elevated blood pressure, lower smoking rates, and lower prevalence of elevated cholesterol than western Europe and North America. These variations mean that the profile of cardiovascular disease differs between low-income and high-income countries. Research in, implementation of, and advocacy for risk reduction of cardiovascular disease in the global context of HIV should account for differences in the distribution of traditional cardiovascular disease risk factors (eg, hypertension, smoking), consider non-traditional cardiovascular disease risk factors (eg, access to antiretroviral therapy with more benign cardiovascular disease side effect profiles, indoor air pollution), and encourage the inclusion of relevant risk reduction approaches for cardiovascular disease in HIV-care guidelines. Future research priorities include implementation science to scale up and expand integrated HIV and cardiovascular disease care models, which have shown promise in sub-Saharan Africa; HIV and cardiovascular disease epidemiology and mechanisms in women; and tobacco cessation for people living with HIV.

Coronary Artery Disease Manifestations in HIV: What, How, and Why.

Understanding why persons with human immunodeficiency virus (HIV) have accelerated atherosclerosis and its sequelae, including coronary artery disease (CAD) and myocardial infarction, is necessary to provide appropriate care to a large and aging population with HIV. In this review, we delineate the diverse pathophysiologies underlying HIV-associated CAD and discuss how these are implicated in the clinical manifestations of CAD among persons with HIV. Several factors contribute to HIV-associated CAD, with chronic inflammation and immune activation likely representing the primary drivers. Increased monocyte activation, inflammation, and hyperlipidemia present in chronic HIV infection also mirror the pathophysiology of plaque rupture. Furthermore, mechanisms central to plaque erosion, such as activation of toll-like receptor 2 and formation of neutrophil extracellular traps, are also abundant in HIV. In addition to inflammation and immune activation in general, persons with HIV have a higher prevalence than uninfected persons of traditional cardiovascular risk factors, including dyslipidemia, hypertension, insulin resistance, and tobacco use. Antiretroviral therapies, although clearly necessary for HIV treatment and survival, have had varied effects on CAD, but newer generation regimens have reduced cardiovascular toxicities. From a clinical standpoint, this mix of risk factors is implicated in earlier CAD among persons with HIV than uninfected persons; whether the distribution and underlying plaque content of CAD for persons with HIV differs considerably from uninfected persons has not been definitively studied. Furthermore, the role of cardiovascular risk estimators in HIV remains unclear, as does the role of traditional and emerging therapies; no trials of CAD therapies powered to detect clinical events have been completed among persons with HIV.

Differences in statin utilization and lipid lowering by race, ethnicity, and HIV status in a real-world cohort of persons with human immunodeficiency virus and uninfected persons.

BACKGROUND: Risks for cardiovascular diseases, including myocardial infarction and stroke, are elevated in people with HIV infection (PWH). However, no trials of statin utilization with clinical cardiovascular disease (CVD) end points have been completed in PWH, and there are sparse real-world data regarding statin use and lipid-lowering effectiveness. We therefore used a unique cohort of PWH and uninfected controls to evaluate (1) differences in statin types used for PWH versus uninfected persons; (2) lipid lowering achieved by statin use for PWH versus uninfected persons; and (3) racial and ethnic disparities in appropriate statin use among PWH and uninfected persons. METHODS: We analyzed a cohort of 5,039 PWH and 10,011 uninfected demographically matched controls who received care at a large urban medical center between January 1, 2000, and May 17, 2017. Medication administration records, prescription data, and validated natural language processing algorithms were used to determine statin utilization. Statins were categorized by generic active ingredient name and intensity (high, moderate, or low). Lipid values collected in routine clinical care were available for analysis. The first set of analyses was restricted to PWH and uninfected matched controls taking statins and compared (1) differences in statin type and (2) difference in cholesterol levels after versus before statin initiation by HIV status. For the second set of analyses, we first used prevalent CVD risk factors to determine participants with statin indications and then determined how many of these participants were taking statins. We then compared statin utilization among persons with indications for statins by race/ethnic group for PWH and uninfected matched controls using multivariable-adjusted logistic regression. RESULTS: Among people prescribed statins, PWH were more likely than controls to have ever taken pravastatin (34.8% vs 12.3%, P < .001) or atorvastatin (72.2% vs 65.6%, P = .002) and less likely to have ever taken simvastatin (14.2% vs 39.5%, P < .001). Among PWH with indications for statin utilization, 55.7% of whites, 39.4% of blacks, and 45.8% of Hispanics were prescribed statins (P < .001). These differences in statin prescription by race/ethnicity remained significant after adjustment for demographics (including insurance status), cardiovascular risk factors, antiretroviral therapy use, HIV viremia, and CD4 count. These racial/ethnic disparities in statin utilization were less pronounced among uninfected persons. CONCLUSIONS: Among PWH with statin indication(s), blacks and Hispanics were less likely than whites to have been prescribed a statin. These racial/ethnic disparities were less pronounced among uninfected persons. There were significant differences in type of statin used for PWH compared to uninfected matched controls. Future efforts addressing disparities in CVD prevention among PWH are warranted.

Clinical characteristics of HIV-infected patients with adjudicated heart failure.

Aims HIV-infected persons may have elevated risks for heart failure, but factors associated with heart failure in the modern era of HIV therapy are insufficiently understood. Despite substantial disagreement between physician-adjudicated heart failure and heart failure diagnosis codes, few studies of HIV cohorts have evaluated adjudicated heart failure. We evaluated associations of HIV viremia, immunosuppression, and cardiovascular risk factors with physician-adjudicated heart failure. Methods and results We analyzed clinical characteristics associated with heart failure in a cohort of 5041 HIV-infected patients receiving care at an urban hospital system between 2000 and 2016. We also evaluated characteristics of HIV-infected patients who screened negative for heart failure, screened positive for possible heart failure but did not have heart failure after adjudication, and had adjudicated heart failure. HIV-infected patients with heart failure ( N = 216) were older and more likely to be black, hypertensive, and have diabetes than HIV-infected patients without heart failure; heart failure with reduced ejection fraction was more common than heart failure with preserved ejection fraction. In our primary analyses restricted to HIV-infected patients whose heart failure diagnoses did not precede their HIV diagnoses ( N = 149), peak HIV viral load ≥100,000 copies/mL (odds ratio (OR) 2.12, 1.28-3.52) and nadir CD4 T-cell count <200 cells/mm3 (OR 2.35, 1.04-5.31) were associated with significantly elevated odds of heart failure. Overall, 30.6% of patients with any diagnosis code of heart failure had adjudicated heart failure. Conclusion Higher peak HIV viremia and lower CD4 cell nadir are associated with significantly elevated odds of heart failure for HIV-infected persons. Physician adjudication of heart failure may be helpful in HIV cohorts.

Types of Myocardial Infarction Among Human Immunodeficiency Virus-Infected Individuals in the United States.

Importance: The Second Universal Definition of Myocardial Infarction (MI) divides MIs into different types. Type 1 MIs result spontaneously from instability of atherosclerotic plaque, whereas type 2 MIs occur in the setting of a mismatch between oxygen demand and supply, as with severe hypotension. Type 2 MIs are uncommon in the general population, but their frequency in human immunodeficiency virus (HIV)-infected individuals is unknown. Objectives: To characterize MIs, including type; identify causes of type 2 MIs; and compare demographic and clinical characteristics among HIV-infected individuals with type 1 vs type 2 MIs. Design, Setting, and Participants: This longitudinal study identified potential MIs among patients with HIV receiving clinical care at 6 US sites from January 1, 1996, to March 1, 2014, using diagnoses and cardiac biomarkers recorded in the centralized data repository. Sites assembled deidentified packets, including physician notes and electrocardiograms, procedures, and clinical laboratory tests. Two physician experts adjudicated each event, categorizing each definite or probable MI as type 1 or type 2 and identifying the causes of type 2 MI. Main Outcomes and Measures: The number and proportion of type 1 vs type 2 MIs, demographic and clinical characteristics among those with type 1 vs type 2 MIs, and the causes of type 2 MIs. Results: Among 571 patients (median age, 49 years [interquartile range, 43-55 years]; 430 men and 141 women) with definite or probable MIs, 288 MIs (50.4%) were type 2 and 283 (49.6%) were type 1. In analyses of type 1 MIs, 79 patients who underwent cardiac interventions, such as coronary artery bypass graft surgery, were also included, totaling 362 patients. Sepsis or bacteremia (100 [34.7%]) and recent use of cocaine or other illicit drugs (39 [13.5%]) were the most common causes of type 2 MIs. A higher proportion of patients with type 2 MIs were younger than 40 years (47 of 288 [16.3%] vs 32 of 362 [8.8%]) and had lower current CD4 cell counts (median, 230 vs 383 cells/µL), lipid levels (mean [SD] total cholesterol level, 167 [63] vs 190 [54] mg/dL, and mean (SD) Framingham risk scores (8% [7%] vs 10% [8%]) than those with type 1 MIs or who underwent cardiac interventions. Conclusions and Relevance: Approximately half of all MIs among HIV-infected individuals were type 2 MIs caused by heterogeneous clinical conditions, including sepsis or bacteremia and recent use of cocaine or other illicit drugs. Demographic characteristics and cardiovascular risk factors among those with type 1 and type 2 MIs differed, suggesting the need to specifically consider type among HIV-infected individuals to further understand MI outcomes and to guide prevention and treatment.