Total Coronary Heart Disease Events Research Articles

Meta-Analysis of 19 Clinical Trials using Omega-3 Fatty Acids Indicate Distinct Outcomes for Icosapent Ethyl

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Consumption of the omega-3 fatty acids (O3FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been associated with a lower risk of cardiovascular disease (CVD). However, randomized clinical trials have failed to show consistent benefit with O3FAs in patients receiving contemporary medical care. Recent trials suggest that the formulation may have an important influence on clinical outcomes. <h3>Objective/Purpose</h3> We conducted a meta-analysis of 19 trials using both mixed O3FA products as well as prescription icosapent ethyl (IPE), which is the ethyl ester of EPA. <h3>Methods</h3> The current meta-analysis includes 15 randomized controlled trials with endpoints including non-fatal myocardial infarction (MI), coronary heart disease (CHD) death, total CHD, CVD death, total CVD, total stroke and major vascular events. The pooled rate ratios (RRs) were calculated using a fixed method. This meta-analysis also includes 4 clinical trials that assess the effect of O3FAs on coronary plaque volume and stability. All trials involved formulations with EPA alone (IPE) or in combination with DHA. <h3>Results</h3> Out of 19 trials using omega-3 fatty acids in patients with CVD risk, 5 of them employed IPE, all of which (100%) met the defined endpoints in statin treated patients. The remaining 14 trials used a combination of EPA and DHA. While only 4 (28%) met the defined endpoint, these trials with mixed O3FAs did not require statin use. <h3>Conclusions</h3> A meta-analysis of 19 CVD trials indicate that only IPE treatment was associated with reduced clinical events in statin-treated patients compared to mixed O3FAs. The basis for the distinct benefits of IPE are not fully understood but appear to be related to broad pleiotropic actions that correlate with on-treatment EPA levels. Elucidating such mechanisms for EPA will provide further insights into our understanding of CVD intervention.

META-ANALYSIS OF 17 CLINICAL TRIALS USING OMEGA-3 FATTY ACIDS IN PATIENTS WITH CARDIOVASCULAR DISEASE

BACKGROUND Cardiovascular disease (CVD) is the primary cause of mortality worldwide. Ischemic events associated with CVD are causatively related to vascular inflammation and atherothrombosis. Certain omega-3 fatty acids, such as eicosapentaenoic acid (EPA), are thought to have anti-inflammatory and anti-thrombotic properties. Icosapent ethyl (IPE) is an ethyl ester of EPA, currently approved by Health Canada as prescription IPE. At 4 g/d, IPE significantly reduced clinical events in high-risk patients with diabetes and other risk factors of CV disease in the REDUCE-IT trial. Previous clinical trials, with the majority of them administering a combination of EPA and the O3FA, docosahexaenoic acid (DHA), have been conducted with mixed outcomes. This study aimed to determine whether O3FA formulations of EPA alone versus mixed combinations can confer protection in patients with CVD. METHODS AND RESULTS The meta-analysis included 13 randomized controlled trials with endpoints including non-fatal myocardial infarction (MI), coronary heart disease (CHD) death, total CHD, CVD death, total CVD, total stroke and major vascular events. The pooled rate ratios (RRs) were calculated using a fixed method. This meta-analysis also included 4 clinical trials that assessed the effect of omega-3 fatty acids on coronary plaque volume and stability. All trials involved formulations with EPA alone or in combination with DHA. Out of 17 trials using omega-3 fatty acids in patients with CVD risk, 5 employed EPA alone, all of which (100%) met the defined endpoints. The remaining 12 trials used a combination of EPA and DHA, of which only 4 (33%) met the defined endpoints, but only in patients where statin use was not prespecified. The differences in outcomes did not correlate with triglyceride lowering. CONCLUSION In a meta-analysis of O3FA trials, the formulation of EPA alone as icosapent ethyl (IPE) was superior to mixtures containing DHA in statin-treated patients. The benefits with IPE are attributed to potential anti-inflammatory, anti-oxidant and anti-thrombotic actions. Elucidating such mechanisms for EPA will lead to further insights into our understanding of atherosclerosis and strategies for CVD treatment. Cardiovascular disease (CVD) is the primary cause of mortality worldwide. Ischemic events associated with CVD are causatively related to vascular inflammation and atherothrombosis. Certain omega-3 fatty acids, such as eicosapentaenoic acid (EPA), are thought to have anti-inflammatory and anti-thrombotic properties. Icosapent ethyl (IPE) is an ethyl ester of EPA, currently approved by Health Canada as prescription IPE. At 4 g/d, IPE significantly reduced clinical events in high-risk patients with diabetes and other risk factors of CV disease in the REDUCE-IT trial. Previous clinical trials, with the majority of them administering a combination of EPA and the O3FA, docosahexaenoic acid (DHA), have been conducted with mixed outcomes. This study aimed to determine whether O3FA formulations of EPA alone versus mixed combinations can confer protection in patients with CVD. The meta-analysis included 13 randomized controlled trials with endpoints including non-fatal myocardial infarction (MI), coronary heart disease (CHD) death, total CHD, CVD death, total CVD, total stroke and major vascular events. The pooled rate ratios (RRs) were calculated using a fixed method. This meta-analysis also included 4 clinical trials that assessed the effect of omega-3 fatty acids on coronary plaque volume and stability. All trials involved formulations with EPA alone or in combination with DHA. Out of 17 trials using omega-3 fatty acids in patients with CVD risk, 5 employed EPA alone, all of which (100%) met the defined endpoints. The remaining 12 trials used a combination of EPA and DHA, of which only 4 (33%) met the defined endpoints, but only in patients where statin use was not prespecified. The differences in outcomes did not correlate with triglyceride lowering. In a meta-analysis of O3FA trials, the formulation of EPA alone as icosapent ethyl (IPE) was superior to mixtures containing DHA in statin-treated patients. The benefits with IPE are attributed to potential anti-inflammatory, anti-oxidant and anti-thrombotic actions. Elucidating such mechanisms for EPA will lead to further insights into our understanding of atherosclerosis and strategies for CVD treatment.

Quantitative Association Between Serum/Dietary Magnesium and Cardiovascular Disease/Coronary Heart Disease Risk: A Dose-Response Meta-analysis of Prospective Cohort Studies.

The quantitative association between serum/dietary magnesium and cardiovascular disease (CVD) remains unclear. We conducted a dose-response meta-analysis to evaluate the quantitative association between serum/dietary magnesium and CVD, including coronary heart disease (CHD). PubMed, China National Knowledge Infrastructure, and Web of Science were searched for publications. STATA 12.0 was used to analyze data. We used the random-effects model to reduce heterogeneity. Eighteen prospective cohort studies with 544,581 participants and 22,658 CVD cases were included. The follow-up duration was 1-28 years. The pooled relative risk (RR) of CVD for the relatively normal versus lowest serum and dietary magnesium level was 0.64 {[95% confidence interval (CI): 0.51-0.80] and 0.90 [95% CI: 0.84-0.96]}. The pooled RR of CHD for the relatively normal versus lowest serum and dietary magnesium level was 0.70 (95% CI: 0.57-0.85) and 0.86 (95% CI: 0.77-0.94). We noted a significant association between increasing serum magnesium levels (per 0.1-mg/dL increase) and risk of CVD (RR: 0.93, 95% CI: 0.88-0.97) and CHD (RR: 0.90, 95% CI: 0.84-0.96) and between dietary magnesium levels (per 100-mg/d increase) and risk of CVD (RR: 0.90, 95% CI: 0.83-0.96) and CHD (RR: 0.92, 95% CI: 0.82-0.98). Serum/dietary Mg level comparisons presented a 7%-10% decrease in CVD/CHD risk. The dose-response meta-analyses showed linear relationships between serum magnesium and CVD (Pnonlinearity = 0.833) or CHD (Pnonlinearity = 0.193) and dietary magnesium and CVD (Pnonlinearity = 0.463) or CHD (Pnonlinearity = 0.440). Increasing dietary magnesium or serum magnesium level is linearly and inversely associated with the risk of total CVD and CHD events.

Marine Omega-3 Supplementation and Cardiovascular Disease: An Updated Meta-Analysis of 13 Randomized Controlled Trials Involving 127 477 Participants.

BackgroundWhether marine omega‐3 supplementation is associated with reduction in risk of cardiovascular disease (CVD) remains controversial.Methods and ResultsThis meta‐analysis included study‐level data from 13 trials. The outcomes of interest included myocardial infarction, coronary heart disease (CHD) death, total CHD, total stroke, CVD death, total CVD, and major vascular events. The unadjusted rate ratios were calculated using a fixed‐effect meta‐analysis. A meta‐regression was conducted to estimate the dose–response relationship between marine omega‐3 dosage and risk of each prespecified outcome. During a mean treatment duration of 5.0 years, 3838 myocardial infarctions, 3008 CHD deaths, 8435 total CHD events, 2683 strokes, 5017 CVD deaths, 15 759 total CVD events, and 16 478 major vascular events were documented. In the analysis excluding REDUCE‐IT (Reduction of Cardiovascular Events with Icosapent Ethyl‐Intervention Trial), marine omega‐3 supplementation was associated with significantly lower risk of myocardial infarction (rate ratio [RR] [95% CI]: 0.92 [0.86, 0.99]; P=0.020), CHD death (RR [95% CI]: 0.92 [0.86, 0.98]; P=0.014), total CHD (RR [95% CI]: 0.95 [0.91, 0.99]; P=0.008), CVD death (RR [95% CI]: 0.93 [0.88, 0.99]; P=0.013), and total CVD (RR [95% CI]: 0.97 [0.94, 0.99]; P=0.015). Inverse associations for all outcomes were strengthened after including REDUCE‐IT while introducing statistically significant heterogeneity. Statistically significant linear dose–response relationships were found for total CVD and major vascular events in the analyses with and without including REDUCE‐IT.ConclusionsMarine omega‐3 supplementation lowers risk for myocardial infarction, CHD death, total CHD, CVD death, and total CVD, even after exclusion of REDUCE‐IT. Risk reductions appeared to be linearly related to marine omega‐3 dose.

Recent Clinical Trials Shed New Light on the Cardiovascular Benefits of Omega-3 Fatty Acids.

Three recent clinical trials have demonstrated the benefits of marine omega-3 fatty acids on cardiovascular disease end points. In the Vitamin D and Omega-3 Trial (VITAL), 840 mg/d of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) resulted in a 28% reduced risk for heart attacks, 50% reduced risk for fatal heart attacks, and 17% reduced risk for total coronary heart disease events. In the ASCEND trial (A Study of Cardiovascular Events in Diabetes), cardiovascular disease death was significantly reduced by 19% with 840 mg/d of EPA and DHA. However, the primary composite end points were not significantly reduced in either study. In REDUCE-IT (the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), there was a 25% decrease in the primary end point of major cardiovascular events with 4 g/d EPA (icosapent ethyl) in patients with elevated triglycerides (135-499 mg/dL) who also were taking a statin drug. For clinical practice, we now have compelling evidence of the cardiovascular benefits of omega-3 fatty acids. The findings of REDUCE-IT provide a strong rationale for prescribing icosapent ethyl for patients with hypertriglyceridemia who are on a statin. For primary prevention, the goal is to increase the population intake of omega-3 fatty acids to levels currently recommended, which translates to consuming at least one to two servings of fish/seafood per week. For individuals who prefer taking omega-3 fatty acid supplements, recent findings from clinical trials support the benefits for primary prevention.

Quantifying Importance of Major Risk Factors for Coronary Heart Disease

To optimize preventive strategies for coronary heart disease (CHD), it is essential to understand and appropriately quantify the contribution of its key risk factors. Our objective was to compare the associations of key modifiable CHD risk factors-specifically lipids, systolic blood pressure (SBP), diabetes mellitus, and smoking-with incident CHD events based on their prognostic performance, attributable risk fractions, and treatment benefits, overall and by age. Pooled participant-level data from 4 observational cohort studies sponsored by the National Heart, Lung, and Blood Institute were used to create a cohort of 22 626 individuals aged 45 to 84 years who were initially free of cardiovascular disease. Individuals were followed for 10 years from baseline evaluation for incident CHD. Proportional hazards regression was used to estimate metrics of prognostic model performance (likelihood ratio, C index, net reclassification, discrimination slope), hazard ratios, and population attributable fractions for SBP, non-high-density lipoprotein cholesterol (non-HDL-C), diabetes mellitus, and smoking. Expected absolute risk reductions for antihypertensive and lipid-lowering treatment were assessed. Age, sex, and race capture 63% to 80% of the prognostic performance of cardiovascular risk models. In contrast, adding either SBP, non-HDL-C, diabetes mellitus, or smoking to a model with other risk factors increases the C index by only 0.004 to 0.013. However, primordial prevention could have a substantial effect as demonstrated by population attributable fractions of 28% for SBP≥130 mm Hg and 17% for non-HDL-C≥130 mg/dL. Similarly, lowering the SBP of all individuals to <130 mm Hg or lowering low-density lipoprotein cholesterol by 30% would be expected to lower a baseline 10-year CHD risk of 10.7% to 7.0 and 8.0, respectively (absolute risk reductions: 3.7% and 2.7%, respectively). Prognostic performance decreases with age (C indices for age groups 45-54, 55-64, 65-74, 75-84 are 0.75, 0.72, 0.66, and 0.62, respectively), whereas absolute risk reductions increase (SBP: 1.1%, 2.3%, 5.4%, 10.3%, respectively; non-HDL-C: 1.1%, 2.0%, 3.7%, 5.9%, respectively). Although individual modifiable CHD risk factors contribute only modestly to prognostic performance, our models indicate that eliminating or controlling these individual factors would lead to substantial reductions in total population CHD events. Metrics used to judge importance of risk factors should be tailored to the research objectives.

Dietary linoleic acid and risk of coronary heart disease: a systematic review and meta-analysis of prospective cohort studies.

Previous studies on intake of linoleic acid (LA), the predominant n-6 fatty acid, and coronary heart disease (CHD) risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of dietary LA intake and CHD risk. We searched MEDLINE and EMBASE databases through June 2013 for prospective cohort studies that reported the association between dietary LA and CHD events. In addition, we used unpublished data from cohort studies in a previous pooling project. We pooled the multivariate-adjusted relative risk (RR) to compare the highest with the lowest categories of LA intake using fixed-effect meta-analysis. We identified 13 published and unpublished cohort studies with a total of 310 602 individuals and 12 479 total CHD events, including 5882 CHD deaths. When the highest category was compared with the lowest category, dietary LA was associated with a 15% lower risk of CHD events (pooled RR, 0.85; 95% confidence intervals, 0.78-0.92; I(2)=35.5%) and a 21% lower risk of CHD deaths (pooled RR, 0.79; 95% confidence intervals, 0.71-0.89; I(2)=0.0%). A 5% of energy increment in LA intake replacing energy from saturated fat intake was associated with a 9% lower risk of CHD events (RR, 0.91; 95% confidence intervals, 0.87-0.96) and a 13% lower risk of CHD deaths (RR, 0.87; 95% confidence intervals, 0.82-0.94). In prospective observational studies, dietary LA intake is inversely associated with CHD risk in a dose-response manner. These data provide support for current recommendations to replace saturated fat with polyunsaturated fat for primary prevention of CHD.

Progression of Coronary Calcium and Incident Coronary Heart Disease Events

The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events. CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression. Progression of CAC is associated with an increased risk for future hard and total CHD events.

Most Important Outcomes Research Papers on Cardiovascular Disease in Women

Cardiovascular disease (CVD) in women has been historically understudied. For many years, heart disease had been thought to be primarily a “man’s disease.” Consequently, women have been significantly under-represented in longitudinal studies of disease history and in clinical trials. High-quality data from women at the extremes of age, with multiple co-morbidities, and from racial and ethnic minorities have been particularly rare. In order to increase awareness of cardiovascular prevention among women, in 1999 the American Heart Association (AHA) published its first women-specific clinical recommendations for the prevention of CVD.1 In 2004, the AHA and multiple other collaborating organizations subsequently sponsored “Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women,” which underwent updates in 2007 and 2011. As a result of these and other related initiatives, the rate of public awareness of CVD as the leading cause of death among US women has increased from 30% in 1997 to 54% in 2009.2 CVD-associated death among US women has declined significantly over this time period.3,4 Yet substantial work still needs to be done to improve women’s cardiovascular health. CVD remains the number one killer among women.4 As the obesity epidemic continues, we are actually finding increases in coronary heart disease (CHD) death among young women 35 to 54 years of age.2 Morbidity and mortality from stroke and hypertension remain high.4 In addition, substantial outcomes disparities continue for women from racial and ethnic minorities.4 We have therefore dedicated our topic summaries in this issue of Circulation: Cardiovascular Quality and Outcomes to CVD in women. We have included only those studies where authors provided a convincing a priori reason to study a particular disease process or clinical intervention in women and reported primary endpoints that were sex-specific. We have included articles on the representation of women …

Clinical usefulness of the metabolic syndrome for the risk of coronary heart disease does not exceed the sum of its individual components in older men and women. The Three-City (3C) Study

ObjectivesTo investigate the respective associations and clinical usefulness of the metabolic syndrome (MetS) and its individual components to predict the risk of first coronary heart disease (CHD) events in elderly.DesignThe...

Meta-Analysis of Multiple Primary Prevention Trials of Cardiovascular Events Using Aspirin

Several meta-analyses have focused on determination of the effectiveness of aspirin (acetylsalicylic acid) in primary prevention of cardiovascular (CV) events. Despite these data, the role of aspirin in primary prevention continues to be investigated. Nine randomized trials have evaluated the benefits of aspirin for the primary prevention of CV events: the British Doctors' Trial (BMD), the Physicians' Health Study (PHS), the Thrombosis Prevention Trial (TPT), the Hypertension Optimal Treatment (HOT) study, the Primary Prevention Project (PPP), the Women's Health Study (WHS), the Aspirin for Asymptomatic Atherosclerosis Trial (AAAT), the Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial, and the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial. The combined sample consists of about 90,000 subjects divided approximately evenly between those taking aspirin and subjects not taking aspirin or taking placebo. A meta-analysis of these 9 trials assessed 6 CV end points: total coronary heart disease, nonfatal myocardial infarction (MI), total CV events, stroke, CV mortality, and all-cause mortality. No covariate adjustment was performed, and appropriate tests for treatment effect, heterogeneity, and study size bias were applied. The meta-analysis suggested superiority of aspirin for total CV events and nonfatal MI, (p <0.05 for each), with nonsignificant results for decreased risk for stroke, CV mortality, and all-cause mortality. There was no evidence of a statistical bias (p >0.05). In conclusion, aspirin decreased the risk for CV events and nonfatal MI in this large sample. Thus, primary prevention with aspirin decreased the risk for total CV events and nonfatal MI, but there were no significant differences in the incidences of stroke, CV mortality, all-cause mortality and total coronary heart disease.

Diabetes and the risk of coronary heart disease in the general Japanese population: The Japan Public Health Center-based prospective (JPHC) study

ObjectiveAlthough diabetes has a great impact on coronary heart disease (CHD) in Western populations, there is limited evidence that diabetes influences CHD in the Japanese population. MethodsThe Japan Public Health Center-based prospective (JPHC) study conducted a follow-up of 31,192 individuals aged 40–69 years with no history of cardiovascular disease or cancer. Subjects were classified at baseline as normal, borderline diabetic or diabetic based on fasting and non-fasting blood glucose levels and the use of medication to treat diabetes. A Cox proportional hazards model was used to determine the association between diabetes and the risk of fatal and non-fatal CHD events after adjustment for potential confounders. ResultsDuring 12.9 years of follow-up (1990–2006), we identified 266 fatal and non-fatal coronary events using validated criteria. With normal individuals serving as a control, the hazard ratios for total incident CHD events after adjusting for sex, age, study community and fasting were 1.65 (95% CI, 1.19–2.29) and 3.05 (2.03–4.59) in the borderline and diabetic groups, respectively. These associations remained significant after adjustment for conventional risk factors. The population attributable fractions (PAF) of borderline diabetes and diabetes for CHD events were 6.9% and 6.3%, respectively. Furthermore, there was a trend for an association between an impaired fasting glucose (5.6–6.9mmol/l) and an increased risk of CHD events. ConclusionsThis prospective study suggests that diabetes and elevated glucose levels are associated with incident CHD in the general Japanese population. The PAF of diabetes for fatal and non-fatal coronary events was estimated to be moderate.

Population Trends of Recurrent Coronary Heart Disease Event Rates Remain High

Survivors of nonfatal coronary heart disease (CHD) can reduce their risk of further events by various preventive interventions. The impact of such measures as delivered over 11 years, on population rates of subsequent major CHD events, has not been extensively studied. This study determined population trends in the prevalence of clinically manifest CHD and the proportion of major CHD events that occur in this population. A population longitudinal person-based event-linked file of CHD extracted from State Hospital Morbidity Data and Death Registry for 1980 to 2005 was used to identify, for each year from 1995 to 2005, survivors who had a hospitalization for CHD over the previous 15 years (population with established CHD), and to examine the occurrence of CHD death and hospitalization with a principal diagnosis of myocardial infarction in both populations with and without established CHD. The average annual age-standardized prevalence of CHD in the Perth metropolitan region (population 1.6 million) was 28 373 (8.8%) in men and 14 966 (4.0%) in women. Age-specific prevalence increased exponentially with age, from <1% in 35 to 39 age group to 42% in 80 to 84 age group in men and half that in women. The percentage of total CHD events (n=28 941) that occurred in the population with established CHD was approximately 43% in both men and women, 55% and 51%, respectively, for CHD death and 35% and 36% for nonfatal myocardial infarction. More than 40% of major CHD events annually occur in persons with manifest disease, highlighting the imperative to implement systems of care that support effective secondary prevention.

Paired Comparison of Observed and Expected Coronary Heart Disease Rates over 12 Years from the Atherosclerosis Risk In Communities Study

To quantify the relationship between coronary heart disease (CHD) risk factor levels and changes over time and population-wide CHD morbidity and mortality. We used a paired cohort and community surveillance of hospitalized myocardial infarction and CHD deaths of community members 53 to 64 years of age in four geographic areas to compare observed community CHD to expected CHD rates and trends based on cohort risk factors. Observed CHD rates declined by 1% to 3% per year in all communities except one, whereas CHD death rates declined 3% to 6% per year in all communities. Risk factor trends predicted a 2% to 3% per year decline in both total events and death. In all communities except one, expected rates of total CHD events were lower than the observed rates, whereas expected and observed CHD death rates were similar. Across all communities women had a higher CHD death rate than expected. Overall, trends in CHD risk factors provide a useful indicator of changes in community event rates and of CHD death, but caution is warranted in prediction of absolute risk of CHD events.

Relation Between the Framingham Risk Score, Coronary Calcium, and Incident Coronary Heart Disease Among Low-Risk Men

The Prospective Army Coronary Calcium Project is evaluating the predictive value of coronary artery calcium (CAC) in unselected, healthy, lower-risk, 40- to 50-year-old men. Although this study has found that coronary calcium is predictive of future coronary heart disease (CHD), criteria are needed to narrow the screening population to those in whom CAC measurement is most efficient (vs unselected screening of low-risk men). In 1,634 unselected volunteer men (mean age 42 years, mean 10-year CHD Framingham risk score [FRS] 4.6%, CAC prevalence 22.4%), we evaluated the independent relation between CAC and incident CHD over 5.6 years including hard events (hospitalized unstable angina, myocardial infarction, and CHD death) and coronary revascularization. The cohort was analyzed in tertiles of FRS for the relation between CAC and CHD outcomes. FRS tertile cutpoints were 0% to 3% (n = 547), >3% to 5% (n = 547), and >5% (n = 540) 10-year CHD risk. Over a mean follow-up of 5.6 +/- 1.5 years (range 1.0 to 8.3), there were 22 total CHD events, including 14 hard events and 8 revascularizations. Most events occurred in the highest FRS tertile (n = 14) versus the middle (n = 6) and lowest (n = 2) risk tertiles (p = 0.005). CAC and CHD events increased across FRS tertiles. Only in the highest FRS tertile was there a significant relation between CAC and CHD outcomes (hazard ratio 9.3). In conclusion, CAC screening could be of benefit in refining risk assessment of low-risk men, but only when the FRS exceeds approximately 5%.

Markers of atherosclerosis and inflammation for prediction of coronary heart disease in older adults.

Although both inflammatory and atherosclerosis markers have been associated with coronary heart disease (CHD) risk, data directly comparing their predictive value are limited. The authors compared the value of 2 atherosclerosis markers (ankle-arm index (AAI) and aortic pulse wave velocity (aPWV)) and 3 inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)) in predicting CHD events. Among 2,191 adults aged 70-79 years at baseline (1997-1998) from the Health, Aging, and Body Composition Study cohort, the authors examined adjudicated incident myocardial infarction or CHD death ("hard" events) and "hard" events plus hospitalization for angina or coronary revascularization (total CHD events). During 8 years of follow-up between 1997-1998 and June 2007, 351 participants developed total CHD events (197 "hard" events). IL-6 (highest quartile vs. lowest: hazard ratio = 1.82, 95% confidence interval: 1.33, 2.49; P-trend < 0.001) and AAI (AAI < or = 0.9 vs. AAI 1.01-1.30: hazard ratio = 1.57, 95% confidence interval: 1.14, 2.18) predicted CHD events above traditional risk factors and modestly improved global measures of predictive accuracy. CRP, TNF-alpha, and aPWV had weaker associations. IL-6 and AAI accurately reclassified 6.6% and 3.3% of participants, respectively (P's < or = 0.05). Results were similar for "hard" CHD, with higher reclassification rates for AAI. IL-6 and AAI are associated with future CHD events beyond traditional risk factors and modestly improve risk prediction in older adults.

Is diabetes a coronary risk equivalent? Systematic review and meta‐analysis

To determine whether patients with diabetes without prior myocardial infarction (MI) have the same risk of total coronary heart disease (CHD) events as non-diabetic patients with previous myocardial infarction. Using MEDLINE, EMBASE, Cochrane and MeSH in this systematic review and meta-analysis, extensive searching was carried out by cross-referencing from original articles and reviews. The study consisted of cohort or observational studies with hard clinical endpoints, including total CHD events (fatal or non-fatal myocardial infarction), stratified for patients with diabetes but no previous myocardial infarction, and patients without diabetes but with previous myocardial infarction. Studies with less than 100 subjects, follow-up of less than 4 years and/or without provisions for calculating CHD event rates were excluded. The review of articles and data extraction was performed by two independent authors, with any disagreements resolved by consensus. Thirteen studies were included involving 45,108 patients. The duration of follow-up was 5-25 years (mean 13.4 years) and the age range was 25-84 years. Patients with diabetes without prior myocardial infarction have a 43% lower risk of developing total CHD events compared with patients without diabetes with previous myocardial infarction (summary odds ratio 0.56, 95% confidence interval 0.53-0.60). This meta-analysis did not support the hypothesis that diabetes is a 'coronary heart disease equivalent'. Public health decisions to initiate cardio-protective drugs in patients with diabetes for primary CHD prevention should therefore be based on appropriate patients' CHD risk estimates rather than a 'blanket' approach of treatment.

Coronary Heart Disease Attributable to Passive Smoking: CHD Policy Model

Passive smoking is a major risk factor for coronary heart disease (CHD), and existing estimates are out of date due to recent and substantial changes in the level of exposure. To estimate the annual clinical burden and cost of CHD treatment attributable to passive smoking. Annual attributable CHD deaths, myocardial infarctions (MI), total CHD events, and the direct cost of CHD treatment. A Monte Carlo simulation estimated the CHD events and costs as a function of the prevalence of CHD risk factors, including passive-smoking prevalence and a low (1.26) and high (1.65) relative risk of CHD due to passive smoking. Estimates were calculated using the CHD Policy Model, calibrated to reproduce key CHD outcomes in the baseline Year 2000 in the U.S. At 1999-2004 levels, passive smoking caused 21,800 (SE=2400) to 75,100 (SE=8000) CHD deaths and 38,100 (SE=4300) to 128,900 (SE=14,000) MIs annually, with a yearly CHD treatment cost of $1.8 (SE=$0.2) to $6.0 (SE=$0.7) billion. If recent trends in the reduction in the prevalence of passive smoking continue from 2000 to 2008, the burden would be reduced by approximately 25%-30%. Passive smoking remains a substantial clinical and economic burden in the U.S.

Predicted coronary risk for adults with coronary heart disease and low HDL-C: an analysis from the US National Health and Nutrition Examination Survey

ABSTRACTPurpose: To assess the national prevalence of low levels of high-density lipoprotein cholesterol (HDL-C) among adults with coronary heart disease (CHD) and the relationship between low HDL-C and predicted rates of recurrent CHD events.Methods: This study used data from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) to examine the prevalence of risk factors for recurrent CHD events among survey respondents with existing CHD. The predicted probability of recurrent CHD events in the next 10 years was estimated using published Framingham Heart Study equations for secondary CHD prevention. All data analyses were weighted to produce national estimates using the NHANES sampling weights.Results: This study included 1291 survey participants aged ≥ 40 years who self-reported having coronary heart disease, angina, or heart attack. Of the study subjects with available HDL-C data, the percentage of respondents who had low HDL-C (< 40 mg/dL), intermediate HDL-C (40 to < 60 mg/dL), and high HDL-C (≥ 60 mg/dL) was 29%, 50%, and 21%, respectively, based on the national weighted population estimate. For respondents with low HDL-C, the prevalence of diabetes in men and the prevalence of smoking in women were significantly higher than those with high HDL-C ( p < 0.05). The predicted 10-year coronary risk for subjects with low HDL-C was considerably higher than for subjects with intermediate and high HDL-C. Although subjects with low HDL-C comprised only 29% of the population, they contributed approximately 38% of the subjects with predicted CHD events.Limitations: The assessment of certain CHD risk factors and the existence of CHD in the NHANES surveys relied on self-reports, which are subject to recall bias.Conclusions: Study results showed that US adults with CHD and low HDL-C will likely contribute a disproportionately high percentage to total CHD events in the next 10 years, suggesting the need for greater awareness of the consequences of low HDL-C.

Japan Arteriosclerosis Longitudinal Study-Existing Cohorts Combine (JALS-ECC)

The Japan Arteriosclerosis Longitudinal Study-Existing Cohorts Combine (JALS-ECC) is a pooled study based on individual participant data from existing prospective cohort studies in Japan. Its purpose was to consider associations between risk factors and cardiovascular disease (CVD) outcomes, as well as differences between subgroups, defined by age, gender or geographical region, which could not be detected in the smaller samples. Individual records for 66,691 participants in 21 cohort studies were pooled, accounting for a total of 575,628 person-years. From this data, there were 409 deaths attributed to stroke and 169 deaths attributed to coronary heart disease (CHD). Total stroke and CHD events were 1,478 and 178, respectively. Of the 1,424 total stroke events with a reported stroke subtype, 975 were classified as ischemic, 267 as hemorrhagic, and 178 as subarachnoid hemorrhage. The JALS-ECC collected data from existing cohort studies covering a diverse Japanese population, which has provided information about the effects of modifiable factors on the risks of the CVD. Such information should provide a reliable basis for establishing prevention strategies.