Higher levels of physical activity are associated with a lower risk of cardiovascular events. Nevertheless, there is debate on the dose-response relationship of exercise and cardiovascular disease ...outcomes and whether high volumes of exercise may accelerate coronary atherosclerosis. We aimed to determine the relationship between lifelong exercise volumes and coronary atherosclerosis.
Middle-aged men engaged in competitive or recreational leisure sports underwent a noncontrast and contrast-enhanced computed tomography scan to assess coronary artery calcification (CAC) and plaque characteristics. Participants reported lifelong exercise history patterns. Exercise volumes were multiplied by metabolic equivalent of task (MET) scores to calculate MET-minutes per week. Participants' activity was categorized as <1000, 1000 to 2000, or >2000 MET-min/wk.
A total of 284 men (age, 55±7 years) were included. CAC was present in 150 of 284 participants (53%) with a median CAC score of 35.8 (interquartile range, 9.3-145.8). Athletes with a lifelong exercise volume >2000 MET-min/wk (n=75) had a significantly higher CAC score (9.4 interquartile range, 0-60.9 versus 0 interquartile range, 0-43.5;
=0.02) and prevalence of CAC (68%; adjusted odds ratio OR
=3.2; 95% confidence interval CI, 1.6-6.6) and plaque (77%; OR
=3.3; 95% CI, 1.6-7.1) compared with <1000 MET-min/wk (n=88; 43% and 56%, respectively). Very vigorous intensity exercise (≥9 MET) was associated with CAC (OR
=1.47; 95% CI, 1.14-1.91) and plaque (OR
=1.56; 95% CI, 1.17-2.08). Among participants with CAC>0, there was no difference in CAC score (
=0.20), area (
=0.21), density (
=0.25), and regions of interest (
=0.20) across exercise volume groups. Among participants with plaque, the most active group (>2000 MET-min/wk) had a lower prevalence of mixed plaques (48% versus 69%; OR
=0.35; 95% CI, 0.15-0.85) and more often had only calcified plaques (38% versus 16%; OR
=3.57; 95% CI, 1.28-9.97) compared with the least active group (<1000 MET-min/wk).
Participants in the >2000 MET-min/wk group had a higher prevalence of CAC and atherosclerotic plaques. The most active group, however, had a more benign composition of plaques, with fewer mixed plaques and more often only calcified plaques. These observations may explain the increased longevity typical of endurance athletes despite the presence of more coronary atherosclerotic plaque in the most active participants.
Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on ...cardiovascular outcomes remain uncertain.
We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects ("statin-intolerant" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary end point was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization.
A total of 13,970 patients underwent randomization; 6992 were assigned to the bempedoic acid group and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients 11.7% vs. 927 13.3%; hazard ratio, 0.87; 95% confidence interval CI, 0.79 to 0.96; P = 0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 8.2% vs. 663 9.5%; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.006); fatal or nonfatal myocardial infarction (261 3.7% vs. 334 4.8%; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = 0.002); and coronary revascularization (435 6.2% vs. 529 7.6%; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = 0.001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels.
Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics; CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.).
Hypertension is a major risk factor for cardiovascular disease and mortality. To identify targets for the prevention of hypertension and its associated disease burden, we used the 2-sample Mendelian ...randomization method to investigate the causal associations of 18 cardiovascular risk factors and lifestyle behaviors with hypertension. From European-descent genome-wide association studies, we selected genetic variants (
<5×10
) for type 2 diabetes, fasting glucose, lipids, body mass index, smoking, alcohol and coffee consumption, physical activity, sleep duration, insomnia, and educational level. We extracted the genetic associations with hypertension from 2 European cohorts: the FinnGen Study (15 870 cases and 74 345 controls) and UK Biobank (54 358 cases and 408 652 controls). The inverse-variance weighted method was used as main analysis method. Genetically predicted triglycerides (pooled odds ratio OR per 1 SD, 1.17 1.10-1.25), body mass index (OR per 1 SD, 1.42 1.37-1.48), alcohol dependence (OR, 1.10 1.06-1.13), and insomnia (OR, 1.17 1.13-1.20) were associated with a higher odds of hypertension. Higher genetically predicted high-density lipoprotein cholesterol (OR per 1 SD, 0.88 0.83-0.94) and educational level (OR per 1 SD, 0.56 0.54-0.59) were associated with a lower odds of hypertension. Suggestive evidence was obtained for type 2 diabetes, smoking initiation and alcohol consumption with a higher hypertension odds, and longer sleep duration with a lower hypertension odds. This Mendelian randomization study identified high-density lipoprotein cholesterol, triglycerides, body mass index, alcohol dependence, insomnia, and educational level as causal risk factors for hypertension. This implicates that these modifiable risk factors are important targets in the prevention of hypertension.
Prediction models are increasingly used to complement clinical reasoning and decision making in modern medicine in general, and in the cardiovascular domain in particular. Developed models first and ...foremost need to provide accurate and (internally and externally) validated estimates of probabilities of specific health conditions or outcomes in targeted patients. The adoption of such models must guide physician's decision making and an individual's behaviour, and consequently improve individual outcomes and the cost-effectiveness of care. In a series of two articles we review the consecutive steps generally advocated for risk prediction model research. This first article focuses on the different aspects of model development studies, from design to reporting, how to estimate a model's predictive performance and the potential optimism in these estimates using internal validation techniques, and how to quantify the added or incremental value of new predictors or biomarkers (of whatever type) to existing predictors. Each step is illustrated with empirical examples from the cardiovascular field.
Uptake of antiretroviral treatment (ART) is expanding rapidly in low- and middle-income countries (LMIC). Monitoring of virological suppression is recommended at 6 months of treatment and annually ...thereafter. In case of confirmed virological failure, a switch to second-line ART is indicated. There is a paucity of data on virological suppression and clinical management of patients experiencing viremia in clinical practice in LMIC. We report a large-scale multicenter assessment of virological suppression over time and management of viremia under programmatic conditions.
Linked medical record and laboratory source data from adult patients on first-line ART at 52 South African centers between 1 January 2007 and 1 May 2018 were studied. Virological suppression, switch to second-line ART, death, and loss to follow-up were analyzed. Multistate models and Cox proportional hazard models were used to assess suppression over time and predictors of treatment outcomes. A total of 104,719 patients were included. Patients were predominantly female (67.6%). Median age was 35.7 years (interquartile range IQR: 29.9-43.0). In on-treatment analysis, suppression below 1,000 copies/mL was 89.0% at month 12 and 90.4% at month 72. Suppression below 50 copies/mL was 73.1% at month 12 and 77.5% at month 72. Intention-to-treat suppression was 75.0% and 64.3% below 1,000 and 50 copies/mL at month 72, respectively. Viremia occurred in 19.8% (20,766/104,719) of patients during a median follow-up of 152 (IQR: 61-265) weeks. Being male and below 35 years of age and having a CD4 count below 200 cells/μL prior to start of ART were risk factors for viremia. After detection of viremia, confirmatory testing took 29 weeks (IQR: 16-54). Viral resuppression to below 1,000 copies/mL without switch of ART occurred frequently (45.6%; 6,030/13,210) but was associated with renewed viral rebound and switch. Of patients with confirmed failure who remained in care, only 41.5% (1,872/4,510) were switched. The median time to switch was 68 weeks (IQR: 35-127), resulting in 12,325 person-years spent with a viral load above 1,000 copies/mL. Limitations of this study include potential missing data, which is in part addressed by the use of cross-matched laboratory source data, and the possibility of unmeasured confounding.
In this study, 90% virological suppression below the threshold of 1,000 copies/mL was observed in on-treatment analysis. However, this target was not met at the 50-copies/mL threshold or in intention-to-treat analysis. Clinical management in response to viremia was profoundly delayed, prolonging the duration of viremia and potential for transmission. Diagnostic tools to establish the cause of viremia are urgently needed to accelerate clinical decision-making.
Measures of interaction on an additive scale (relative excess risk due to interaction RERI, attributable proportion AP, synergy index S), were developed for risk factors rather than preventive ...factors. It has been suggested that preventive factors should be recoded to risk factors before calculating these measures. We aimed to show that these measures are problematic with preventive factors prior to recoding, and to clarify the recoding method to be used to circumvent these problems. Recoding of preventive factors should be done such that the stratum with the lowest risk becomes the reference category when both factors are considered jointly (rather than one at a time). We used data from a case-control study on the interaction between ACE inhibitors and the ACE gene on incident diabetes. Use of ACE inhibitors was a preventive factor and DD ACE genotype was a risk factor. Before recoding, the RERI, AP and S showed inconsistent results (RERI = 0.26 95% CI: -0.30; 0.82, AP = 0.30 95% CI: -0.28; 0.88, S = 0.35 95% CI: 0.02; 7.38), with the first two measures suggesting positive interaction and the third negative interaction. After recoding the use of ACE inhibitors, they showed consistent results (RERI = -0.37 95% CI: -1.23; 0.49, AP = -0.29 95% CI: -0.98; 0.40, S = 0.43 95% CI: 0.07; 2.60), all indicating negative interaction. Preventive factors should not be used to calculate measures of interaction on an additive scale without recoding.
Most patients with cardiovascular disease (CVD) do not take recommended medications long-term. The use of fixed-dose combinations (FDCs) improves adherence in several clinical areas. Previous trials ...of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment.
To assess whether FDC delivery of aspirin, statin, and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors, systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C).
The UMPIRE trial, a randomized, open-label, blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe. The trial follow-up concluded in July 2012.
Participants were randomly assigned (1:1) to an FDC-based strategy (n=1002) containing either (1) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol or (2) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide or to usual care (n=1002).
Adherence to medication (defined as self-reported use of antiplatelet, statin, and ≥2 BP-lowering medications) and changes in SBP and LDL-C from baseline.
At baseline, mean BP was 137/78 mm Hg, LDL-C was 91.5 mg/dL, and 1233 (61.5%) of 2004 participants reported use of antiplatelet, statin, and 2 or more BP-lowering medications. Median follow-up was 15 months (interquartile range, 12-18 months). The FDC group had improved adherence vs usual care (86% vs 65%; relative risk RR of being adherent, 1.33; 95% CI, 1.26-1.41; P < .001) with concurrent reductions in SBP (-2.6 mm Hg; 95% CI, -4.0 to -1.1 mm Hg; P < .001) and LDL-C (-4.2 mg/dL; 95% CI, -6.6 to -1.9 mg/dL; P < .001) at the end of the study. Although there was consistency of effects across predefined subgroups, evidence existed of larger benefits in patients with lower adherence at baseline. In this subgroup of 727 participants (36%), adherence at the end of study was 77% vs 23% (RR, 3.35; 95% CI, 2.74-4.09; P < .001 for interaction), SBP was reduced by 4.9 mm Hg (95% CI 7.3-2.6 mm Hg; P = .01 for interaction), and LDL-C was reduced by 6.7 mg/dL (95% CI, 10.5-2.8 mg/dL; P = .11 for interaction). There were no significant differences in serious adverse events or cardiovascular events (50 5% in the FDC group and 35 3.5% in the usual care group; RR, 1.45; 95% CI, 0.94-2.24; P=.09) between the groups.
Among patients with or at high risk of CVD, use of an FDC strategy for blood pressure, cholesterol, and platelet control vs usual care resulted in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C.
clinicaltrials.gov Identifier: NCT01057537.
Diabetes is largely a self-managed disease; thus, care outcomes are closely linked to self-management behaviours. Structured self-management education (DSME) interventions are, however, largely ...unavailable in Africa.
We sought to characterise DSME interventions in two urban low-resource primary settings; and to explore diabetes self-management knowledge and behaviours, of persons living with diabetes (PLD).
A convergent parallel mixed-methods study was conducted between January and February 2021 in Accra, Ghana. The sampling methods used for selecting participants were total enumeration, consecutive sampling, purposive and judgemental sampling. Multivariable regression models were used to study the association between diabetes self-management knowledge and behaviours. We employed inductive content analysis of informants' experiences and context, to complement the quantitative findings.
In total, 425 PLD (70.1% (n = 298) females, mean age 58 years (SD 12), with a mean blood glucose of 9.4 mmol/l (SD 6.4)) participated in the quantitative study. Two managers, five professionals, two diabetes experts and 16 PLD participated in in-depth interviews. Finally, 24 PLD were involved in four focus group discussions. The median diabetes self-management knowledge score was 40% ((IQR 20-60). For every one unit increase in diabetes self-management knowledge, there were corresponding increases in the diet (5%;95% CI: 2%-9%, p<0.05), exercise (5%; 95% CI:2%-8%, p<0.05) and glucose monitoring (4%;95% CI:2%-5%, p<0.05) domains of the diabetes self-care activities scale respectively. The DSME interventions studied, were unstructured and limited by resources. Financial constraints, conflicting messages, beliefs, and stigma were the themes underpinning self-management behaviour.
The DSME interventions studied were under-resourced, and unstructured. Diabetes self-management knowledge though limited, was associated with self-management behaviour. DSME interventions in low resource settings should be culturally tailored and should incorporate sessions on mitigating financial constraints. Future studies should focus on creating structured DSME interventions suited to resource-constrained settings.
PDF
