Search

BackgroundExcessive inflammation persists despite antiretroviral treatment. Statins decrease cardiovascular (CV) disease risk by reducing low-density lipoprotein cholesterol and inflammation. We performed an exploratory analysis to evaluate whether statin therapy decreased risk of non-AIDS-defining events and nonaccidental death.MethodsA total of 3601 subjects not on a statin from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort were included. Outcome was time to first clinical event (CV event, renal or hepatic disease, incident diabetes, thrombotic/embolic event, nontraumatic fracture, non-AIDS-defining malignancy, serious bacterial infection, or nonaccidental death); event categories were also analyzed separately. Inverse probability of treatment and censoring weighted Cox proportional hazard models were used to assess the causal statin effect. Differential statin effects by baseline covariates were evaluated.ResultsOver 15 135 person-years (PY) of follow-up, 484 subjects initiated statins; 616 experienced an event (crude event rate, 4.4/100 PY on a statin and 4.1/100 PY not on a statin); the unadjusted hazard ratio (HR) was 1.17 (95% confidence interval [CI], .91-1.50). In a final weighted model, the adjusted HR (AHR) was 0.81 (95% CI, .53- 1.24). Results for other clinical events were similar, except for malignancies (AHR, 0.43 [95% CI, .19-.94]) and bacterial infections (AHR, 1.30 [95% CI, .64-2.65]). No differential statin effects by baseline covariates were detected.ConclusionsAlthough statin therapy was not associated with a reduction in time to all non-AIDS-defining event or nonaccidental death, it was associated with a statistically significant 57% reduction in non-AIDS-defining malignancies. Confirmatory studies are needed to evaluate statin-associated reduction in risk of cancer and non-AIDS-associated morbidities.

Research shows that certain antihypertensives taken during midlife confer Alzheimer's disease (AD) related benefits in later life. We conducted a clinical trial to evaluate the extent to which the angiotensin converting enzyme inhibitor (ACE-I), ramipril, affects AD biomarkers including cerebrospinal fluid (CSF) amyloid-β (Aβ) levels and ACE activity, arterial function, and cognition in participants with a parental history of AD. This four month randomized, double-blind, placebo-controlled, pilot clinical trial evaluated the effects of ramipril, a blood-brain-barrier crossing ACE-I, in cognitively healthy individuals with mild, or Stage I hypertension. Fourteen participants were stratified by gender and apolipoprotein E ε4 (APOE ε4) status and randomized to receive 5 mg of ramipril or matching placebo daily. Participants were assessed at baseline and month 4 on measures of CSF Aβ(1-42) and ACE activity, arterial function, and cognition. Participants were middle-aged (mean 54 y) and highly educated (mean 15.4 y), and included 50% men and 50% APOE ε4 carriers. While results did not show a treatment effect on CSF Aβ(1-42) (p = 0.836), data revealed that ramipril can inhibit CSF ACE activity (p = 0.009) and improve blood pressure, however, there were no differences between groups in arterial function or cognition. In this study, ramipril therapy inhibited CSF ACE activity and improved blood pressure, but did not influence CSF Aβ1-42. While larger trials are needed to confirm our CSF Aβ results, it is possible that prior research reporting benefits of ACE-I during midlife may be attributed to alternative mechanisms including improvements in cerebral blood flow or the prevention of angiotensin II-mediated inhibition of acetylcholine. [ABSTRACT FROM AUTHOR]

Background: It remains debated whether to include resting electrocardiogram (ECG) in the routine care of human immunodeficiency virus (HIV)-infected patients.Methods: This analysis included 4518 HIV-infected patients (28% women and 29% blacks) from the Strategies for Management of Antiretroviral Therapy study, a clinical trial aimed to compare 2 HIV treatment strategies. ECG abnormalities were classified using the Minnesota Code. Cox proportional hazards analysis was used to examine the association between baseline ECG abnormalities and incident cardiovascular disease (CVD).Results: More than half of the participants (n = 2325, or 51.5%) had either minor or major ECG abnormalities. Minor ECG abnormalities (48.6%) were more common than major ECG abnormalities (7.7%). During a median follow-up of 28.7 months, 155 participants (3.4%) developed incident CVD. After adjusting for the study-treatment arms, the presence of major, minor, and either minor or major ECG abnormalities was significantly predictive of incident CVD (hazard ratio [95% confidence interval]: 2.76 [1.74-4.39], P < .001; 1.58 [1.14-2.20], P = .006; 1.57 [1.14-2.18], P = .006, respectively). However, after adjusting for demographics, CVD risk factors, and HIV characteristics (full model), presence of major ECG abnormalities were still significantly predictive of CVD (1.83 [1.12-2.97], P = .015) but not minor or major abnormalities taken together (1.26 [0.89-1.79], P = .18; 1.25 [0.89-1.76], P = .20, respectively). Individual ECG abnormalities that significantly predicted CVD in the fully adjusted model included major isolated ST-T abnormalities, major prolongation of QT interval, minor isolated ST-T, and minor isolated Q-QS abnormalities.Conclusion: Nearly 1 in 2 of the HIV-infected patients in our study had ECG abnormalities; 1 in 13 had major ECG abnormalities. Presence of ECG abnormalities, especially major ECG abnormalities, was independently predictive of incident CVD. These results suggest that the ECG could provide a convenient risk-screening tool in HIV-infected patients. [ABSTRACT FROM AUTHOR]

Context: Neither supervised treadmill exercise nor strength training for patients with peripheral arterial disease (PAD) without intermittent claudication have been established as beneficial.Objective: To determine whether supervised treadmill exercise or lower extremity resistance training improve functional performance of patients with PAD with or without claudication.Design, Setting, and Participants: Randomized controlled clinical trial performed at an urban academic medical center between April 1, 2004, and August 8, 2008, involving 156 patients with PAD who were randomly assigned to supervised treadmill exercise, to lower extremity resistance training, or to a control group.Main Outcome Measures: Six-minute walk performance and the short physical performance battery. Secondary outcomes were brachial artery flow-mediated dilation, treadmill walking performance, the Walking Impairment Questionnaire, and the 36-Item Short Form Health Survey physical functioning (SF-36 PF) score.Results: For the 6-minute walk, those in the supervised treadmill exercise group increased their distance walked by 35.9 m (95% confidence interval [CI], 15.3-56.5 m; P < .001) compared with the control group, whereas those in the resistance training group increased their distance walked by 12.4 m (95% CI, -8.42 to 33.3 m; P = .24) compared with the control group. Neither exercise group improved its short physical performance battery scores. For brachial artery flow-mediated dilation, those in the treadmill group had a mean improvement of 1.53% (95% CI, 0.35%-2.70%; P = .02) compared with the control group. The treadmill group had greater increases in maximal treadmill walking time (3.44 minutes; 95% CI, 2.05-4.84 minutes; P < .001); walking impairment distance score (10.7; 95% CI, 1.56-19.9; P = .02); and SF-36 PF score (7.5; 95% CI, 0.00-15.0; P = .02) than the control group. The resistance training group had greater increases in maximal treadmill walking time (1.90 minutes; 95% CI, 0.49-3.31 minutes; P = .009); walking impairment scores for distance (6.92; 95% CI, 1.07-12.8; P = .02) and stair climbing (10.4; 95% CI, 0.00-20.8; P = .03); and SF-36 PF score (7.5; 95% CI, 0.0-15.0; P = .04) than the control group.Conclusions: Supervised treadmill training improved 6-minute walk performance, treadmill walking performance, brachial artery flow-mediated dilation, and quality of life but did not improve the short physical performance battery scores of PAD participants with and without intermittent claudication. Lower extremity resistance training improved functional performance measured by treadmill walking, quality of life, and stair climbing ability.Trial Registration: clinicaltrials.gov Identifier: NCT00106327. [ABSTRACT FROM AUTHOR]

Background: Statins reduce amyloid-beta (Abeta) levels in the brain and cerebrospinal fluid (CSF) in animals and may thereby favorably alter the pathobiology of AD. It is unclear if statins modify Abeta metabolism or improve cognition in asymptomatic middle-aged adults at increased risk for AD.Methods: In a 4-month randomized, double-blind, controlled study, we evaluated the effects of simvastatin 40 mg daily vs. placebo on CSF Abeta42 levels and cognition in 57 asymptomatic middle-aged adult children of persons with AD.Results: Compared to placebo, individuals randomized to simvastatin for 4 months had similar changes in CSF Abeta42 (p=0.344) and total tau levels (p=0.226), yet greater improvements in some measures of verbal fluency (p=0.024) and working memory (p=0.015). APOE4 genotype, gender, and vascular risk factors were associated with CSF biomarker levels, but did not modify treatment effects.Conclusion: In asymptomatic middle-aged adults at increased risk for AD, simvastatin use improved selected measures of cognitive function without significantly changing CSF Abeta42 or total tau levels. Further studies are needed to clarify the impact of higher dose and/or longer duration statin therapy on not only Abeta metabolism, but also other preclinical processes related to the development of AD. [ABSTRACT FROM AUTHOR]

Although human immunodeficiency virus (HIV) protease inhibitors (PIs) improve survival in patients with HIV infection, many patients receiving PIs develop hyperlipidemia, which may increase risk of future coronary events. The purpose of this study was to estimate the changing prevalence of lipid-lowering therapy (LLT) in patients with HIV and to evaluate its association with the use of HIV PIs. This was a cross-sectional study of adults with HIV infection who were registered in the Medicaid of California (MEDI-CAL) administrative claims database. Frequencies of HIV-related and dyslipidemia diagnoses were determined from International Classification of Diseases-9th Edition codes. Use of lipid-lowering and antiretroviral medications was determined by National Drug Codes. Multivariate statistical techniques were used to evaluate trends in use of PIs and lipid-lowering medications from January 1996 to June 2002. The number of HIV-infected patients in MEDI-CAL ranged from 15,764 in 1996 to 13,349 in 2000. The prevalence of LLT use among HIV-infected patients on PIs increased by sixfold (1.7% to 10.6%, p <0.05), and in 2000, exceeded use in the overall MEDI-CAL population (p = 0.09). The increasing rate of LLT in patients taking PIs was greater than in HIV-infected patients not on PIs and in MEDI-CAL (p = 0.002). In multivariate models, increasing age (odds ratio 2.30) and use of PIs (odds ratio 2.08) predicted use of LLT (p <0.001). Thus, in patients taking HIV PIs, use of LLT increased more than sixfold, at a faster rate than in the general population. It has not been proved that use of LLT in HIV-infected patients taking PIs improves survival. [ABSTRACT FROM AUTHOR]

Patients may be requesting referrals for electron-beam CT, but the medical community is still debating the test's usefulness. What do we know about this controversial technology's ability to detect coronary artery disease? [ABSTRACT FROM AUTHOR]

Research increasingly indicates that trying to correct an unfavorable lipid profile in patients older than 60 is well worth the effort. Here are the reasons why -- and a structured approach to the problem. [ABSTRACT FROM AUTHOR]

Clinical estimates of right atrial pressure from the jugular venous pulse were accurate when right atrial pressure was normal, but systematically underestimated elevated right atrial pressures. Because the increased distance from the mid-right atrium to the sternal angle is not accounted for, apparently normal right atrial pressure estimates by this technique do not reliably exclude elevated right atrial pressure in patients with congestive heart failure. [ABSTRACT FROM AUTHOR]

Patients may be requesting referrals for electron-beam CT, but the medical community is still debating the test's usefulness. What do we know about this controversial technology's ability to detect coronary artery disease? [ABSTRACT FROM AUTHOR]

Importance: Smoking is the leading preventable cause of death and illness in the US. Identifying cost-effective smoking cessation treatment may increase the likelihood that health systems deliver such treatment to their patients who smoke., Objective: To evaluate the cost-effectiveness of standard vs enhanced varenicline use (extended varenicline treatment or varenicline in combination with nicotine replacement therapy) among individuals trying to quit smoking., Design, Setting, and Participants: This economic evaluation assesses the Quitting Using Intensive Treatments Study (QUITS), which randomized 1251 study participants who smoked into 4 conditions: (1) 12-week varenicline monotherapy (n = 315); (2) 24-week varenicline monotherapy (n = 311); (3) 12-week varenicline combination treatment with nicotine replacement therapy patch (n = 314); or (4) 24-week varenicline combination treatment with nicotine replacement therapy patch (n = 311). Study enrollment occurred in Madison and Milwaukee, Wisconsin, between November 11, 2017, and July 2, 2020. Statistical analysis took place from May to October 2023., Main Outcomes and Measures: The primary outcome was 7-day point prevalence abstinence (biochemically confirmed with exhaled carbon monoxide level ≤5 ppm) at 52 weeks. The incremental cost-effectiveness ratio (ICER), or cost per additional person who quit smoking, was calculated using decision tree analysis based on abstinence and cost for each arm of the trial., Results: Of the 1251 participants, mean (SD) age was 49.1 (11.9) years, 675 (54.0%) were women, and 881 (70.4%) completed the 52-week follow-up. Tobacco cessation at 52 weeks was 25.1% (79 of 315) for 12-week monotherapy, 24.4% (76 of 311) for 24-week monotherapy, 23.6% (74 of 314) for 12-week combination therapy, and 25.1% (78 of 311) for 24-week combination therapy, respectively. The total mean (SD) cost was $1175 ($365) for 12-week monotherapy, $1374 ($412) for 12-week combination therapy, $2022 ($813) for 24-week monotherapy, and $2118 ($1058) for 24-week combination therapy. The ICER for 12-week varenicline monotherapy was $4681 per individual who quit smoking and $4579 per quality-adjusted life-year (QALY) added. The ICER for 24-week varenicline combination therapy relative to 12-week monotherapy was $92 000 000 per additional individual who quit smoking and $90 000 000 (95% CI, $15 703 to dominated or more costly and less efficacious) per additional QALY., Conclusions and Relevance: This economic evaluation of standard vs enhanced varenicline treatment for smoking cessation suggests that 12-week varenicline monotherapy was the most cost-effective treatment option at the commonly cited threshold of $100 000/QALY. This study provides patients, health care professionals, and other stakeholders with increased understanding of the health and economic impact of more intensive varenicline treatment options.

Background: 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., Methods and Results: 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., Conclusions: 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.