Elevated plasma apolipoprotein E levels in people living with HIV: Associations with biomarkers and HIV-specific risk factors.

BACKGROUND AND AIMS: Apolipoprotein E (apoE) plays a crucial role in cholesterol metabolism, and high levels of apoE in plasma are associated with cardiovascular disease and all-cause mortality. We aimed to assess if HIV is independently associated with high plasma apoE and to determine HIV-related risk factors for high plasma apoE. METHODS: We included 661 people with HIV (PWH) from the Copenhagen Comorbidity in HIV (COCOMO) study with available measurement of plasma apoE. COCOMO participants were frequency matched 1:1 on age and sex with controls from the Copenhagen General Population Study. High plasma apoE was defined as levels above the 90th percentile (66.2 mg/L). The association between HIV and high plasma apoE was assessed using logistic regression models. Among PWH, both linear and logistic regression models were used to determine HIV-specific risk factors for high plasma apoE. RESULTS: Mean age was 52 years and 89 % were male. Median plasma apoE was 49.0 mg/L in PWH and 43.3 mg/L in controls, p < 0.001. HIV was associated with higher plasma apoE after adjusting for potential confounders, including triglycerides (odds ratio 2.14 [95 % CI: 1.39-3.29], p < 0.001). In PWH, higher plasma apoE was associated with a previous AIDS-defining condition in linear models before adjustment for triglycerides and integrase strand transfer inhibitor use in fully adjusted linear models. CONCLUSIONS: PWH had higher plasma apoE than controls even after adjusting for triglycerides. Further studies are needed to elucidate the clinical impact of high plasma apoE in PWH.

The Interplay between Adipose Tissue Properties and Levels of NT-proBNP in People with HIV.

Objective: We aimed to assess the association between low N-terminal pro-brain natriuretic peptide (NT-proBNP) and body mass index (BMI), adipose tissue distribution, adiponectin, and HIV-specific risk factors among people with HIV (PWH). Methods: We included 811 PWH with measurement of height, weight and waist circumference, blood samples analyzed for NT-proBNP, and visceral-(VAT) and subcutaneous (SAT) adipose tissue areas measured from CT-scans. Low concentrations of NT-proBNP were defined as concentrations below the limit of quantification (5.9 pmol/L). Associations were explored with multivariable logistic regression analyses adjusted for relevant confounders. Results: We identified 471 (58%) individuals with low concentrations of NT-proBNP. Increasing BMI was associated with higher odds of low NT-proBNP (adjusted OR (aOR) 1.06 (95% CI: 1.01-1.11) per 1 kg/m2). Central obesity and large areas of VAT were associated with higher odds of low NT-proBNP (aOR 1.66 (1.16-2.36) and aOR 1.69 (1.09-2.62), respectively). Higher adiponectin was associated with lower odds of low NT-proBNP (aOR 0.86 (0.79-0.95) per 10% increase). No associations were found between low NT-proBNP and HIV-specific risk factors. Conclusions: In PWH, low NT-proBNP is associated with an adverse adipose tissue profile with high BMI, central obesity, accumulation of VAT, and low adiponectin.

Global longitudinal strain predicts atrial fibrillation in individuals without hypertension: A Community-based cohort study.

BACKGROUND: Global longitudinal strain (GLS) is a sensitive marker of myocardial dysfunction and atrial reservoir function. We sought to evaluate its value for predicting atrial fibrillation (AF) in the general population. METHODS: Participants from the Copenhagen City Heart Study examined with echocardiography, including speckle tracking analyses, were included. The endpoint was AF obtained through national registries. Proportional hazards Cox regression was applied, including multivariable adjustments made for CHADS2 and CHARGE-AF risk factors. Abnormal GLS was defined as >-18%. RESULTS: The data from 1,309 participants were analyzed. Of those, 153 (12%) developed AF during a median follow-up time of 15.9 years. The follow-up was 100%. The mean age was 57 years, 38% had hypertension, and GLS was  - 18%. In unadjusted analysis, GLS was a univariable predictor of outcome (1.08 (1.04-1.13), p < 0.001, per 1% absolute decrease), but did not remain an independent predictor after adjusting for neither CHADS2 nor CHARGE-AF risk factors. However, hypertension modified the relationship between GLS and AF (p for interaction = 0.010), such that GLS only predicted AF in subjects without hypertension. In participants without hypertension, GLS remained an independent predictor of AF after adjusting for CHADS2 and CHARGE-AF (HR = 1.11 (1.03-1.20) and HR = 1.09 (1.01-1.19), respectively). In these participants, an abnormal GLS was associated with a more than twofold increased risk of AF (HR = 2.16 (1.26-3.72). The incidence rate was 3.17 and 6.81 per 1000 person-years for normal vs. abnormal GLS, respectively. CONCLUSION: Global longitudinal strain predicts AF in individuals without hypertension from the general population, independently of common risk scores.

Association of Left Ventricular Systolic Function With Incident Heart Failure in Late Life.

Importance: Limited data exist regarding the association of subtle subclinical systolic dysfunction and incident heart failure (HF) in late life. Objective: To assess the independent associations of subclinical impairments in systolic performance with incident HF in late life. Design, Setting, and Participants: This study was a time-to-event analysis of participants without heart failure in the Atherosclerosis Risk in Communities (ARIC) study, a prospective, community-based cohort study, who underwent protocol echocardiography at the fifth study visit (January 1, 2011, to December 31, 2013). Findings were validated independently in participants in the Copenhagen City Heart Study (CCHS). Data analysis was performed from June 1, 2018, to February 28, 2020. Exposures: Left ventricular ejection fraction (LVEF), longitudinal strain (LS), and circumferential strain (CS) measured by 2-dimensional and strain echocardiography. Main Outcomes and Measures: Main outcomes were incident adjudicated HF and HF with preserved and reduced LVEF at a median follow-up of 5.5 years (interquartile range, 5.0-5.8 years). Cox proportional hazards regression models adjusted for demographics, hypertension, diabetes, obesity, smoking, coronary disease, estimated glomerular filtration rate, LV mass index, e', E/e', and left atrial volume index. Lower 10th percentile limits were determined in 374 participants free of cardiovascular disease or risk factors. Results: Among 4960 ARIC participants (mean [SD] age, 75 [5] years; 2933 [59.0%] female; 965 [19%] Black), LVEF was less than 50% in only 76 (1.5%). In the 3552 participants with complete assessment of LVEF, LS, and CS, 983 (27.7%) had 1 or more of the following findings: LVEF less than 60%, LS less than 16.0%, or CS less than 23.7%. Modeled continuously or dichotomized, worse LVEF, LS, and CS were each independently associated with incident HF. The adjusted hazard ratio (HR) per SD decrease in LVEF was 1.41 (95% CI, 1.29-1.55); the HR for LVEF less than 60% was 2.59 (95% CI, 1.99-3.37). Similar findings were observed for continuous LS (HR, 1.37; 95% CI, 1.22-1.53) and dichotomized LS (HR, 1.93; 95% CI, 1.46-2.55) and for continuous CS (HR, 1.39; 95% CI, 1.22-1.57) and dichotomized CS (HR, 2.30; 95% CI, 1.64-3.22). Although the magnitude of risk for incident HF or death associated with impaired LVEF was greater using guideline (HR, 2.99; 95% CI, 2.19-4.09) compared with ARIC-based limits (HR, 1.88; 95% CI, 1.58-2.25), the number of participants classified as impaired was less (104 [2.1%] based on guideline thresholds compared with 692 [13.9%] based on LVEF <60%). The population-attributable risk associated with LVEF less than 60% was 11% compared with 5% using guideline-based limits, a finding replicated in 908 participants in the CCHS. Conclusions and Relevance: These findings suggest that relatively subtle impairments of systolic function (detected based on LVEF or strain) are independently associated with incident HF and HF with reduced LVEF in late life. Current recommended assessments of LV function may substantially underestimate the prevalence of prognostically important impairments in systolic function in this population.