HIV-infected patients have an increased risk of cardiovascular disease (CVD). Impaired endothelial function is an early risk factor for CVD in the general population. It is presumed that HIV ...infection is associated with impaired endothelial function, but results have been inconsistent.
Our objectives were to determine the relationships between HIV infection, virologic suppression with antiretroviral therapy (ART), in vivo measures of conduit artery and microvascular endothelial function, and circulating biomarkers of pathways associated with CVD.
We performed a cross-sectional analysis of three prospectively enrolled groups from a single center: 28 were HIV-infected and virologically-suppressed on a regimen of FTC/TDF/EFV (HIV+ART+), 44 were HIV-infected but not on ART (HIV+ART-), and 39 were HIV-uninfected healthy volunteers (HIV-) matched to the HIV+ART- group for age, sex, smoking status, and height. None had diabetes, uncontrolled hypertension, known CVD, or other pro-inflammatory condition. Flow mediated dilation (FMD), nitroglycerin-mediated dilation (NTGMD), reactive hyperemia velocity time integral (RHVTI), and FMD/RHVTI of the brachial artery were measured, as well as circulating biomarkers of systemic inflammation, metabolism, oxidative stress, and endothelial activation.
No significant differences were found amongst the three groups in FMD (P = 0.46), NTGMD (P = 0.42), RHVTI (P = 0.17), and FMD/RHVTI (P = 0.22) in unadjusted comparisons. Adjusted ANOVA models which included brachial artery diameter, demographics, and conventional CVD risk factors did not appreciably change these findings. In pairwise comparisons, the HIV+ART- group had significantly higher soluble tumor necrosis factor receptor II, soluble CD163, β-2 microglobulin, interferon-γ- induced protein-10, tissue inhibitor of metalloproteinase-1, and vascular cell adhesion molecule-1 compared to the other two groups (all p<0.05). Correlates of endothelial function differed between study groups.
Although untreated HIV infection was associated with elevated levels of several biomarkers of inflammation and endothelial activation, we were unable to demonstrate differences in measures of conduit artery and microvascular endothelial function in this study population.
Background
Coronary artery calcium (CAC) predicts coronary heart disease (CHD) events better than carotid wall plaque presence; however, differences in the utility of CAC burden and carotid plaque ...burden across the spectrum of cardiovascular disease (CVD) events is unknown.
Methods and Results
CVD, CHD and stroke/transient ischemic attack (TIA) events were evaluated prospectively in a multiethnic cohort without CVD at baseline. Carotid plaque score was determined by the number of ultrasound‐detected plaques in the common, bifurcation, and internal carotid artery segments. CAC was detected by computed tomography. Predictive values were compared using Cox proportional hazards models, C‐statistics, and net reclassification, adjusting for traditional CVD risk factors. At baseline, the 4955 participants were mean (SD) 61.6 (10.1) years old and 52.8% female; 48.9% had CAC >0 and 50.8% had at least 1 carotid plaque. After 11.3 (3.0) years of follow‐up, 709 CVD, 498 CHD, and 262 stroke/TIA events occurred. CAC score compared to carotid plaque score was a stronger predictor of CVD (hazard ratio HR, 1.78; 95% CI, 1.16–1.98; P<0.001 vs HR, 1.27; 95% CI, 1.16–1.40; P<0.001) and CHD events (HR, 2.09; 95% CI, 1.84–2.38; P<0.001 vs HR, 1.35; 95% CI, 1.21–1.51; P<0.001). CAC score and carotid plaque score were weak predictors of stroke/TIA. CAC score had better reclassification statistics than carotid plaque score, except for stroke/TIA, which had similar predictive values.
Conclusions
CAC score improved prediction, discrimination, and reclassification of CVD and CHD better than carotid ultrasound measures, although prediction and discrimination were similar for stroke/TIA.
Smoking cessation medications are routinely used in health care. Research suggests that combining varenicline with the nicotine patch, extending the duration of varenicline treatment, or both, may ...increase cessation effectiveness.
To compare combinations of varenicline plus the nicotine or placebo patch vs combinations used for either 12 weeks (standard duration) or 24 weeks (extended duration).
Double-blind, 2 × 2 factorial randomized clinical trial conducted from November 11, 2017, to July 9, 2020, at 1 research clinic in Madison, Wisconsin, and at 1 clinic in Milwaukee, Wisconsin. Of the 5836 adults asked to participate in the study, 1251 who smoked 5 cigarettes/d or more were randomized.
All participants received cessation counseling and were randomized to 1 of 4 medication groups: varenicline monotherapy for 12 weeks (n = 315), varenicline plus nicotine patch for 12 weeks (n = 314), varenicline monotherapy for 24 weeks (n = 311), or varenicline plus nicotine patch for 24 weeks (n = 311).
The primary outcome was carbon monoxide-confirmed self-reported 7-day point prevalence abstinence at 52 weeks.
Among 1251 patients who were randomized (mean SD age, 49.1 11.9 years; 675 54.0% women), 751 (60.0%) completed treatment and 881 (70.4%) provided final follow-up. For the primary outcome, there was no significant interaction between the 2 treatment factors of medication type and medication duration (odds ratio OR, 1.03 95% CI, 0.91 to 1.17; P = .66). For patients randomized to 24-week vs 12-week treatment duration, the primary outcome occurred in 24.8% (154/622) vs 24.3% (153/629), respectively (risk difference, -0.4% 95% CI, -5.2% to 4.3%; OR, 1.01 95% CI, 0.89 to 1.15). For patients randomized to varenicline combination therapy vs varenicline monotherapy, the primary outcome occurred in 24.3% (152/625) vs 24.8% (155/626), respectively (risk difference, 0.4% 95% CI, -4.3% to 5.2%; OR, 0.99 95% CI, 0.87 to 1.12). Nausea occurrence ranged from 24.0% to 30.9% and insomnia occurrence ranged from 24.4% to 30.5% across the 4 groups.
Among adults smoking 5 cigarettes/d or more, there were no significant differences in 7-day point prevalence abstinence at 52 weeks among those treated with combined varenicline plus nicotine patch therapy vs varenicline monotherapy, or among those treated for 24 weeks vs 12 weeks. These findings do not support the use of combined therapy or of extended treatment duration.
ClinicalTrials.gov Identifier: NCT03176784.
Long-term ozone (Formula: see text) exposure is associated with cardiovascular mortality, but little is known about the associations between Formula: see text and subclinical arterial disease.
We ...studied the longitudinal association of exposure to Formula: see text and progression of key subclinical arterial markers in adults: intima-media thickness of common carotid artery (Formula: see text), carotid plaque (CP) burden, and coronary artery calcification (CAC).
CAC was measured one to four times at baseline and at follow-up exams (1999–2012) by computed tomography (CT) in 6,619 healthy adults, recruited at age 45-84 y without cardiovascular disease (CVD), over a mean of 6.5 y (standard deviation: 3.5 y). Formula: see text and CP burden were quantified in 3,392 participants using carotid artery ultrasound imaging acquired over a mean of 9 y (1.7 y). Over 91% and 89% participants had at least one follow-up Formula: see text and CAC measurement, respectively. Residence-specific Formula: see text concentrations were estimated by a validated spatiotemporal model spanning from 1999 to 2012. This model relied on comprehensive monitoring data and geographical variables to predict individualized long-term average concentrations since baseline. Linear mixed models and logistic regression model were used to evaluate relationships of long-term average exposure to Formula: see text with longitudinal change in Formula: see text, CAC, and CP formation, respectively.
Mean progression rates of Formula: see text and CAC were Formula: see text and Formula: see text. CP formation was identified in 55% of the subjects. A Formula: see text increase in long-term average Formula: see text exposure was associated with a Formula: see text 95% confidence interval (CI): 1.4, 9.7 greater increase in Formula: see text over 10 y. A Formula: see text increase in Formula: see text was also associated with new CP formation odds ratio (OR): 1.2 (95% CI: 1.1, 1.4) but not CAC progression Formula: see text (95% CI: Formula: see text, 2). Associations were robust in the analysis with extended covariate adjustment, including copollutants, i.e., nitrogen oxides (Formula: see text) and particulate matter with diameter Formula: see text (Formula: see text).
Over almost a decade of follow-up, outdoor Formula: see text concentrations were associated with increased rate of carotid wall thickness progression and risk of new plaque formation, suggesting arterial injury in this cohort. https://doi.org/10.1289/EHP3325.
Smoking cessation medications are routinely used in health care; it is vital to identify medications that most effectively treat this leading cause of preventable mortality.
To compare the efficacies ...of varenicline, combination nicotine replacement therapy (C-NRT), and the nicotine patch for 26-week quit rates.
Three-group randomized intention-to-treat clinical trial occurring from May 2012 to November 2015 among smokers recruited in the Madison, Wisconsin, and Milwaukee, Wisconsin, communities; 65.5% of smokers offered the study (2687/4102) refused participation prior to randomization.
Participants were randomized to one of three 12-week open-label smoking cessation pharmacotherapy groups: (1) nicotine patch only (n = 241); (2) varenicline only (including 1 prequit week; n = 424); and (3) C-NRT (nicotine patch + nicotine lozenge; n = 421). Six counseling sessions were offered.
The primary outcome was carbon monoxide-confirmed self-reported 7-day point-prevalence abstinence at 26 weeks. Secondary outcomes were carbon monoxide-confirmed self-reported initial abstinence, prolonged abstinence at 26 weeks, and point-prevalence abstinence at weeks 4, 12, and 52.
Among 1086 smokers randomized (52% women; 67% white; mean age, 48 years; mean of 17 cigarettes smoked per day), 917 (84%) provided 12-month follow-up data. Treatments did not differ on any abstinence outcome measure at 26 or 52 weeks, including point-prevalence abstinence at 26 weeks (nicotine patch, 22.8% 55/241; varenicline, 23.6% 100/424; and C-NRT, 26.8% 113/421) or at 52 weeks (nicotine patch, 20.8% 50/241; varenicline, 19.1% 81/424; and C-NRT, 20.2% 85/421). At 26 weeks, the risk differences for abstinence were, for patch vs varenicline, -0.76% (95% CI, -7.4% to 5.9%); for patch vs C-NRT, -4.0% (95% CI, -10.8% to 2.8%); and for varenicline vs C-NRT, -3.3% (95% CI, -9.1% to 2.6%). All medications were well tolerated, but varenicline produced more frequent adverse events than did the nicotine patch for vivid dreams, insomnia, nausea, constipation, sleepiness, and indigestion.
Among adults motivated to quit smoking, 12 weeks of open-label treatment with nicotine patch, varenicline, or C-NRT produced no significant differences in biochemically confirmed rates of smoking abstinence at 26 weeks. The results raise questions about the relative effectiveness of intense smoking pharmacotherapies.
clinicaltrials.gov Identifier: NCT01553084.
Carotid intima-media thickness (cIMT) and carotid plaque are reliable indicators of cardiovascular disease risk, and research highlights that racial and ethnic minority individuals generally exhibit ...higher cIMT and carotid plaque than White individuals. At present, the mechanisms driving these disparities among different racial and ethnic and biological sex groups are poorly understood.
Data came from the baseline examination of MESA (Multi-Ethnic Study of Atherosclerosis). A total of 6814 participants aged 45 to 84 years free of clinical cardiovascular disease completed assessments on health behavior and perceived discrimination. Four sex-stratified moderated mediation models examined associations between discrimination, cigarette smoking, and mean cIMT and plaque. We hypothesized that cigarette use would mediate the association between discrimination and carotid artery disease features, and that these would differ by race and ethnicity. Indirect effects of discrimination on plaque were observed among Hispanic women such that discrimination was associated with cigarette use and, in turn, higher plaque (β=0.04 95% CI, 0.01-0.08). Indirect effects of discrimination on mean cIMT were found among Hispanic (β=0.003 95% CI, 0.0001-0.007) and White men (β=0.04 95% CI, 0.01-0.08) such that discrimination was associated with cigarette use and, in turn, higher cIMT. Finally, a positive indirect effect of discrimination on plaque was observed among Hispanic men (β=0.03 95% CI, 0.004-0.07). No other racial and ethnic differences were observed.
To understand and address social determinants of cardiovascular disease, researchers must incorporate an intersectional framework that will allow us to understand the complex nature of discrimination and cardiovascular disease risk for individuals of varying intersecting identities and social positions.
Background. Fat gain after antiretroviral therapy (ART) occurs, and its association with protease inhibitors (PIs) is unclear. Methods. Peripheral and central fat depots and lean mass were measured ...using standardized and centrally read abdominal CT scans and whole-body dual-energy absorptiometry scans over a 96-week period in human immunodeficiency virus (HIV)–infected treatment-naive participants. The patients were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) in ACTG A5260s, a substudy of A5257. Within arm changes were assessed with signed-rank tests. The 96-week percentage changes in fat and lean mass in the 2 PI arms were not different, thus the PI arms were combined and compared to the RAL arm. Associations between baseline biomarkers and changes in body composition were assessed. All analyses used linear regression models. Results. 328 patients were randomized (90% male, 44% white non-Hispanic). The median age was 36 years, HIV-1 RNA 4.6 log 10 copies/mL, and CD4 349 cells/μL. Overall, at week 96, increases in limb fat (13.4%), subcutaneous (19.9%) and visceral abdominal fat (25.8%), trunk fat (18%), and lean mass (1.8%) were apparent (P< .001 for changes within each arm). Changes for all fat and lean outcomes were not different between the PI arms or between the RAL and the combined PI arms. Higher baseline HIV-1 RNA levels were associated with greater gains in peripheral and central fat. Conclusions. In treatment-naive participants initiating ART with TDF/FTC, no differences in lean mass and regional fat were found with RAL when compared with ATV/r or DRV/r over 96 weeks. Clinical Trials Registration. NCT00811954 and NCT00851799.
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