Impact of Diabetes Mellitus on the Evaluation of Stable Chest Pain Patients: Insights From the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) Trial

Background: The impact of diabetes mellitus on the clinical presentation and noninvasive test (NIT) results among stable outpatients presenting with symptoms suggestive of coronary artery disease (CAD) has not been well described. Methods and Results: The PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial enrolled 10 003 patients with known diabetic status, of whom 8966 were tested as randomized and had interpretable NIT results (1908 with diabetes mellitus, 21%). Differences in symptoms and NIT results were evaluated using logistic regression. Patients with diabetes mellitus (versus without) were similar in age (median 61 versus 60 years) and sex (female 54% versus 52%), had a greater burden of cardiovascular comorbidities, and had a similar likelihood of nonchest pain symptoms (29% versus 27%). The Diamond‐Forrester/Coronary Artery Surgery Study score predicted that patients with diabetes mellitus (versus without) had similar likelihood of obstructive CAD (low 1.8% versus 2.7%; intermediate 92.3% versus 92.6%; high 5.9% versus 4.7%). Physicians estimated patients with diabetes mellitus to have a higher likelihood of obstructive CAD (low to very low: 28.3% versus 40.1%; intermediate 63.9% versus 55.9%; high to very high 7.8% versus 4.0%). Patients with diabetes mellitus (versus without) were more likely to have a positive NIT result (15% versus 11%; adjusted odds ratio, 1.23; P=0.01). Conclusions: Stable chest pain patients with and without diabetes mellitus have similar presentation and pretest likelihood of obstructive CAD; however, physicians perceive that patients with diabetes mellitus have a higher pretest likelihood of obstructive CAD, an assessment supported by increased risk of a positive NIT. Further evaluation of diabetes mellitus's influence on CAD assessment is required. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes

BACKGROUND The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338.

Cardiovascular Diseases in India Compared With the United States.

This review describes trends in the burden of cardiovascular diseases (CVDs) and risk factors in India compared with the United States; provides potential explanations for these differences; and describes strategies to improve cardiovascular health behaviors, systems, and policies in India. The prevalence of CVD in India has risen over the past 2 decades due to population growth, aging, and a stable age-adjusted CVD mortality rate. Over the same time period, the United States has experienced an overall decline in age-adjusted CVD mortality, although the trend has begun to plateau. These improvements in CVD mortality in the United States are largely due to favorable population-level risk factor trends, specifically with regard to tobacco use, cholesterol, and blood pressure, although improvements in secondary prevention and acute care have also contributed. To realize similar gains in reducing premature death and disability from CVD, India needs to implement population-level policies while strengthening and integrating its local, regional, and national health systems. Achieving universal health coverage that includes financial risk protection should remain a goal to help all Indians realize their right to health

High-sensitivity C-reactive protein elevation in patients with prior myocardial infarction in the United States

ImportanceThe extent to which levels of high-sensitivity C-reactive protein (hs-CRP), a known marker of increased cardiovascular risk, are elevated and are associated with standard cardiovascular risk factors in patients with a history of myocardial infarction (MI) is unknown.ObjectivesTo determine the pattern and determinants of the distribution of hs-CRP in those with a prior MI in the United States using a nationally representative sample.Design and participantsAdults with hs-CRP data in the National Health and Nutrition Examination Surveys from 1999-2010.ResultsAmong 1296 individuals in our cohort, the median age was 65 years and the median hs-CRP level was 2.69 mg/L, measured an average of 7.1 years after the MI. Among these patients, 22% had hs-CRP levels of &lt;1 mg/L, 61% had ≥2 mg/L, and 48% had ≥3 mg/L. Increasing hs-CRP was associated in a multivariable model with increasing body mass index (partial R2 [pR2] 0.113, P &lt; .001), increasing non-high-density lipoprotein [HDL] (pR2 0.030, P &lt; .001), increasing age (pR2 0.008, P = .017), and decreasing HDL (pR2 0.005, P = .046). Adjusted mean hs-CRP was also higher in women (3.6 vs 2.7 mg/L; P &lt; .001), in people with hypertension (3.5 vs. 2.8, P = .030), and among smokers (4.2 vs 2.3 mg/L; P &lt; .001), and lower in people with hyperlipidemia (2.8 vs. 3.5, P = .007). Standard cardiovascular risk factors accounted for only 22% of the variability in hs-CRP levels.Conclusions and relevanceAmong patients with prior MI, elevated hs-CRP is prevalent several years after the MI, and standard cardiovascular risk factors explain only a small proportion of hs-CRP variability. In light of emerging evidence on the importance of inflammation in the pathogenesis of cardiovascular disease, the high prevalence of elevated hs-CRP in patients with prior MI in the United States may have public health implications

Long-Term Mortality of Older Patients With Acute Myocardial Infarction Treated in US Clinical Practice.

BackgroundThere is limited information about the long-term survival of older patients after myocardial infarction (MI).Methods and resultsCRUSADE (Can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines) was a registry of MI patients treated at 568 US hospitals from 2001 to 2006. We linked MI patients aged ≥65&nbsp;years in CRUSADE to their Medicare data to ascertain long-term mortality (defined as 8 years post index event). Long-term unadjusted Kaplan-Meier mortality curves were examined among patients stratified by revascularization status. A landmark analysis conditioned on surviving the first year post-MI was conducted. We used multivariable Cox regression to compare mortality risks between ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction patients. Among 22&nbsp;295 MI patients ≥ age 65 years (median age 77&nbsp;years), we observed high rates of evidence-based medication use at discharge: aspirin 95%, β-blockers 94%, and statins 81%. Despite this, mortality rates were high: 24% at 1&nbsp;year, 51% at 5&nbsp;years, and 65% at 8&nbsp;years. Eight-year mortality remained high among patients who underwent percutaneous coronary intervention (49%), coronary artery bypass graft (46%), and among patients who survived the first year post-MI (59%). Median survival was 4.8&nbsp;years (25th, 75th percentiles 1.1, 8.5); among patients aged 65-74&nbsp;years it was 8.2&nbsp;years (3.3, 8.9) while for patients aged ≥75&nbsp;years it was 3.1&nbsp;years (0.6, 7.6). Eight-year mortality was lower among ST-segment-elevation myocardial infarction than non-ST-segment-elevation myocardial infarction patients (53% versus 67%); this difference was not significant after adjustment (hazard ratio 0.94, 95% confidence interval, 0.88-1.00).ConclusionsLong-term mortality remains high among patients with MI in routine clinical practice, even among revascularized patients and those who survived the first year

Long-Term Mortality of Older Patients With Acute Myocardial Infarction Treated in US Clinical Practice.

BackgroundThere is limited information about the long-term survival of older patients after myocardial infarction (MI).Methods and resultsCRUSADE (Can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines) was a registry of MI patients treated at 568 US hospitals from 2001 to 2006. We linked MI patients aged ≥65 years in CRUSADE to their Medicare data to ascertain long-term mortality (defined as 8 years post index event). Long-term unadjusted Kaplan-Meier mortality curves were examined among patients stratified by revascularization status. A landmark analysis conditioned on surviving the first year post-MI was conducted. We used multivariable Cox regression to compare mortality risks between ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction patients. Among 22 295 MI patients ≥ age 65 years (median age 77 years), we observed high rates of evidence-based medication use at discharge: aspirin 95%, β-blockers 94%, and statins 81%. Despite this, mortality rates were high: 24% at 1 year, 51% at 5 years, and 65% at 8 years. Eight-year mortality remained high among patients who underwent percutaneous coronary intervention (49%), coronary artery bypass graft (46%), and among patients who survived the first year post-MI (59%). Median survival was 4.8 years (25th, 75th percentiles 1.1, 8.5); among patients aged 65-74 years it was 8.2 years (3.3, 8.9) while for patients aged ≥75 years it was 3.1 years (0.6, 7.6). Eight-year mortality was lower among ST-segment-elevation myocardial infarction than non-ST-segment-elevation myocardial infarction patients (53% versus 67%); this difference was not significant after adjustment (hazard ratio 0.94, 95% confidence interval, 0.88-1.00).ConclusionsLong-term mortality remains high among patients with MI in routine clinical practice, even among revascularized patients and those who survived the first year

Worth their weight? An update on new and emerging pharmacologic agents for obesity and their potential role for persons with cardiac conditions

Obesity is associated with cardiovascular (CV) conditions, including but not limited to atherosclerotic disease, heart failure, and atrial fibrillation. Despite this, the impact of intentional weight loss on CV outcomes for persons with obesity and established CV conditions remains poorly studied. New and emerging pharmacologic therapies for weight loss primarily targeting the incretin/nutrient sensing axes induce substantial and sustained weight loss. The glucagon-like-peptide 1 receptor agonists (GLP-1 RA) liraglutide and semaglutide have US FDA approval for the treatment of obesity, and the application for an obesity indication for the dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide is presently under FDA review. Extensive phase II and IIIa randomized controlled trials are underway evaluating permutations of combined GLP-1 RA, GIP receptor agonist, GIP receptor antagonist, and glucagon receptor agonists. Clinical outcome trials of these therapies in persons with obesity at high risk of established CV conditions should make it possible to estimate the role of intentional weight loss in managing CV risk via these medications. High-dose once weekly injectable semaglutide (2.4 mg/week) use among persons with obesity and heart failure with preserved ejection fraction was effective at both reducing weight and improving health status; exercise capacity was also improved. Ongoing CV outcome trials of oral semaglutide and once weekly injectable tirzepatide will help to establish the role of these therapies among persons with other CV conditions. In addition to these two therapies targeting a CV claim or indication, many other new therapeutics for weight loss, as reviewed, are currently in development. The impact of pharmacologic-induced weight loss on CV conditions for persons with obesity and established CV conditions is currently under investigation for multiple agents. These therapies may offer new avenues to manage CV risk in persons with obesity and with established or at high risk for CV disease