Reducing the Global Burden of Cardiovascular Disease, Part 2: Prevention and Treatment of Cardiovascular Disease.

In this second part of a 2-part series on the global burden of cardiovascular disease, we review the proven, effective approaches to the prevention and treatment of cardiovascular disease. We specifically review the management of acute cardiovascular diseases, including acute coronary syndromes and stroke; the care of cardiovascular disease in the ambulatory setting, including medical strategies for vascular disease, atrial fibrillation, and heart failure; surgical strategies for arterial revascularization, rheumatic and other valvular heart disease, and symptomatic bradyarrhythmia; and approaches to the prevention of cardiovascular disease, including lifestyle factors, blood pressure control, cholesterol-lowering, antithrombotic therapy, and fixed-dose combination therapy. We also discuss cardiovascular disease prevention in diabetes mellitus; digital health interventions; the importance of socioeconomic status and universal health coverage. We review building capacity for conduction cardiovascular intervention through strengthening healthcare systems, priority setting, and the role of cost effectiveness.

Assessing the quality of published genetic association studies in meta-analyses: the quality of genetic studies (Q-Genie) tool.

BACKGROUND: Advances in genomics technology have led to a dramatic increase in the number of published genetic association studies. Systematic reviews and meta-analyses are a common method of synthesizing findings and providing reliable estimates of the effect of a genetic variant on a trait of interest. However, summary estimates are subject to bias due to the varying methodological quality of individual studies. We embarked on an effort to develop and evaluate a tool that assesses the quality of published genetic association studies. Performance characteristics (i.e. validity, reliability, and item discrimination) were evaluated using a sample of thirty studies randomly selected from a previously conducted systematic review. RESULTS: The tool demonstrates excellent psychometric properties and generates a quality score for each study with corresponding ratings of 'low', 'moderate', or 'high' quality. We applied our tool to a published systematic review to exclude studies of low quality, and found a decrease in heterogeneity and an increase in precision of summary estimates. CONCLUSION: This tool can be used in systematic reviews to inform the selection of studies for inclusion, to conduct sensitivity analyses, and to perform meta-regressions.

Impact of lifestyle factors on fracture risk in older patients with cardiovascular disease: a prospective cohort study of 26,335 individuals from 40 countries.

BACKGROUND: fractures are a major health concern among the elderly. People at risk for cardiovascular disease (CVD) are at an increased risk for fractures. The aim of this study was to assess the individual and combined effect of the CVD risk factors of smoking, alcohol consumption and physical activity on fracture risk in a large sample of older individuals with CVD or diabetes with end-organ damage. METHODS: we analysed data for 26,335 adults, aged 55 years or older, who participated in two large antihypertensive drug treatment trials and who had no previous fracture at baseline. Lifestyle factors were assessed by the standardised questionnaire and their individual and combined effects on incident fracture risk were modelled using Cox proportional hazard regression. RESULTS: during the 56-month follow-up, 1,079 incident fractures occurred; 508 (6.51%) among women and 571 (3.08%) among men. Smoking [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.27-1.82] and low physical activity (HR: 1.19, 95% CI: 1.05-1.36) were associated with an increased risk of any fracture, while high alcohol intake showed a directional, but non-significant, relationship with fracture risk (HR: 1.09, 95% CI: 0.64-1.84). Compared with participants with no lifestyle risk factors, those having one, two, or three risk factors had an increased risk of a future fracture (HR: 1.17, 95% CI: 1.03-1.34 for one risk factor; HR: 1.73, 95% CI: 1.38-2.16 for two risk factors; and HR: 2.37, 95% CI: 0.88-6.36 for three risk factors; P for trend <0.001). CONCLUSIONS: a healthier lifestyle advocated to reduce the risk of CVD is associated with a significant and graded reduction in fracture risk.

Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153 152 middle-aged individuals.

AIMS: To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine antithrombotic use and clinical outcomes. METHODS AND RESULTS: Baseline ECGs were collected in 153 152 middle-aged participants (ages 35-70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow-up of 7.4 years) were available in one cohort. Cross-sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China, and Southeast Asia (270-360 cases per 100 000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100 000 persons) (P < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs) (P < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received antithrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke [hazard ratio (HR) 2.29; 95% confidence interval (CI) 1.49-3.52] and death (HR 2.97; 95% CI 2.25-3.93); with similar rates in different countries grouped by income level. CONCLUSIONS: Large variations in AF prevalence occur in different regions and countries grouped by income level, but this is only partially explained by traditional AF risk factors. Antithrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.

From ACE Inhibitors/ARBs to ARNIs in Coronary Artery Disease and Heart Failure (Part 2/5).

The pharmacological inhibition of the renin-angiotensin-aldosterone system as a therapeutic strategy is one of the most significant advances in the treatment and prevention of cardiovascular disease in heart failure with reduced ejection fraction and in coronary artery disease. Recently, the addition of neprilysin inhibition to angiotensin receptor blockade has been shown to be even more effective than angiotensin-converting enzyme inhibition alone in heart failure with reduced ejection fraction, marking an important new milestone in heart failure treatment. This review summarizes the major trials that have informed the clinical role of inhibition of the renin-angiotensin-aldosterone and neprilysin pathways, as well as the limitations of these strategies.

Impact of a Genetic Risk Score on Myocardial Infarction Risk Across Different Ethnic Populations.

BACKGROUND: Myocardial infarction (MI) risk varies by ethnicity, although the influence of genetic factors remains unclear. Using a genetic risk score (GRS), we examined the association between 25 coronary artery disease (CAD)-related single nucleotide polymorphisms and MI across 6 ethnic groups. METHODS: We studied 8556 participants in the INTERHEART case-control study from 6 ethnic groups: Europeans, South Asians, Southeast Asians, Arabs, Latin Americans, and Africans. Associations between the GRS and MI were tested in each group by logistic regression and overall by meta-analysis. RESULTS: Overall, the GRS increased the odds of MI by 1.07 (95% confidence interval [CI], 1.04-1.09) per risk allele in the unadjusted model, with little change (odds ratio, 1.06; 95% CI, 1.04-1.09) after adjusting for demographic and modifiable factors. In Europeans, South Asians, Southeast Asians, and Arabs, the GRS was significantly associated with MI, with minimal heterogeneity observed. In these groups, a score > 23 risk alleles (highest 4 quintiles) was associated with only a 5% difference in population attributable risk (PAR) (36% to 41%) for MI. The GRS was not significant in Latin Americans or Africans. In the overall cohort, modest changes, beyond clinical factors, in PAR (88% to 91%), concordance statistic (0.73 to 0.74), and continuous net reclassification improvement (12%) were observed with the GRS. CONCLUSIONS: A CAD GRS is associated with MI across a multiethnic cohort, with significant and consistent effects across 4 distinct ethnicities. However, it only modestly improves MI risk prediction beyond clinical factors.

Pharmacogenetics in cardiovascular disease: the challenge of moving from promise to realization: concepts discussed at the Canadian Network and Centre for Trials Internationally Network Conference (CANNeCTIN), June 2009.

Pharmacogenetics in cardiovascular medicine brings the potential for personalized therapeutic strategies that improve efficacy and reduce harm. Studies evaluating the impact of genetic variation on pharmacologic effects have been undertaken for most major cardiovascular drugs, including antithrombotic agents, ß-adrenergic receptor blockers, statins, and angiotensin-converting enzyme inhibitors. Across these drug classes, many polymorphisms associated with pharmacodynamic, pharmacokinetic, or surrogate outcomes have been identified. However, their impact on clinical outcomes and their ability to improve clinical practice remains unclear. This review will examine the current clinical evidence supporting pharmacogenetic testing in cardiovascular medicine, provide clinical guidance based on the current evidence, and identify further steps needed to determine the utility of pharmacogenetics in cardiovascular care.

The mini-mental state examination, clinical factors, and motor vehicle crash risk.

OBJECTIVES: To examine the association between Mini-Mental State Examination (MMSE) score and motor vehicle crash (MVC) risk in a large cohort of community-dwelling participants with cardiovascular disease (CVD) or diabetes mellitus. DESIGN: Prospective observational study. SETTING: Participants enrolled in the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial and Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease clinical trial, which included individuals aged 55 and older with CVD or diabetes mellitus. PARTICIPANTS: Totally 17,538 frequent drivers (defined as driving at least once per week) who had completed a baseline MMSE. MEASUREMENTS: Involvement in a MVC as the driver. RESULTS: Baseline MMSE score was divided into four categories: 30, 27-29, 24-26, and <24. The median MMSE score was 29 (interquartile range 27-30), and 726 (4.1%) has a MMSE score of less than 24 at baseline. After a mean follow-up of 4.5 years, 1,068 (6.1%) participants were drivers in a MVC. Lower scores were not associated with future MVCs (MMSE score 29-27, hazard ratio (HR)=1.06, 95% confidence interval (CI)=0.93-1.22); MMSE score 26-24, HR=0.96, 95% CI=0.78-1.19; MMSE score<24, HR=0.72, 95% CI=0.50-1.05) on multivariable analysis. A MVC within the previous 2 years (HR=2.68, 95% CI=2.29-3.13) was the strongest predictor of future MVCs. Other clinical factors associated with greater MVC risk were depression, falls within the previous year, sleep apnea, and lower baseline systolic blood pressure. CONCLUSION: In a population of frequent drivers, the MMSE does not predict MVCs. Other clinical factors have a stronger association with MVC risk.

Exploring gene-environment relationships in cardiovascular disease.

Identifying gene-environment interactions that affect cardiovascular disease or associated cardiometabolic diseases may identify novel pathways of cardiovascular disease development, and improve our understanding of how genetic factors impact cardiovascular risk. Several studies have identified environmental or behavioural factors that alter genetic risks associated with cardiovascular disease, lipid traits, diabetes/metabolic syndrome, obesity, and hypertension. Though some interactions have been consistently observed, most require replication in additional studies. Moreover, further research is needed to identify the mechanisms underlying these interactions, and their clinical impact. This review will examine the current evidence supporting gene-environment interactions in cardiometabolic diseases, and highlight additional steps that are needed to determine the clinical utility of these observations.