Objectives The study sought to determine the 99th percentile upper reference limit for the high-sensitivity cardiac troponin T assay (hs-cTnT) in 3 large independent cohorts. Background The presently ...recommended 14 ng/l cut point for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization. Methods Data were included from 3 well-characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS). Within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease, and kidney disease (subcohort 1), and further excluding those with subclinical structural heart disease (subcohort 2). Data were analyzed stratified by age, sex, and race. Results The 99th percentile values for the hs-cTnT assay in DHS, ARIC, and CHS were 18, 22, and 36 ng/l (subcohort 1) and 14, 21, and 28 ng/l (subcohort 2), respectively. These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men 65 to 74 years of age with no cardiovascular disease in our study had cardiac troponin T values above the current myocardial infarction threshold. Conclusions Use of a uniform 14 ng/l cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay.
Objectives This study sought to examine the efficacy of ranolazine versus placebo on weekly angina frequency and sublingual nitroglycerin use in subjects with type 2 diabetes mellitus, coronary ...artery disease (CAD), and chronic stable angina who remain symptomatic despite treatment with up to 2 antianginal agents. Background Patients with diabetes have more extensive CAD than those without diabetes, and a high burden of angina. Ranolazine is not only effective in treating angina but also may improve glycemic control, thus providing several potential benefits in this high-risk group. We conducted a randomized trial to test the antianginal benefit of ranolazine in patients with diabetes and stable angina. Methods TERISA (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina) was an international, randomized, double-blind trial of ranolazine versus placebo in patients with diabetes, CAD, and stable angina treated with 1 to 2 antianginals. After a single-blind, 4-week placebo run-in, patients were randomized to 8 weeks of double-blind ranolazine (target dose 1000 mg bid) or placebo. Anginal episodes and nitroglycerin use were recorded with daily entry into a novel electronic diary. Primary outcome was the average weekly number of anginal episodes over the last 6 weeks of the study. Results A total of 949 patients were randomized across 104 centers in 14 countries. Mean age was 64 years, 61% were men, mean diabetes duration was 7.5 years, and mean baseline HbA1c was 7.3%. Electronic diary data capture was 98% in both groups. Weekly angina frequency was significantly lower with ranolazine versus placebo (3.8 95% confidence interval (CI): 3.6 to 4.1 episodes vs. 4.3 95% CI: 4.0 to 4.5 episodes, p = 0.008), as was the weekly sublingual nitroglycerin use (1.7 95% CI: 1.6 to 1.9 doses vs. 2.1 95% CI: 1.9 to 2.3 doses, p = 0.003). There was no difference in the incidence of serious adverse events between groups. Conclusions Among patients with diabetes and chronic angina despite treatment with up to 2 agents, ranolazine reduced angina and sublingual nitroglycerin use and was well tolerated. (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina TERISA; NCT01425359 )
The primary outcome was a composite of a first or subsequent CVD event: cardiovascular death; myocardial infarction, hospitalized unstable angina, or coronary revascularization; ischemic stroke, ...transient ischemic attack, or cerebrovascular revascularization; peripheral arterial revascularization; hospitalization for heart failure; or hospitalization for atrial fibrillation. Multivariate-adjusted marginal Cox proportional hazards modeling using the Wei-Lin-Weissfeld method for recurrent events (2) was used to calculate hazard ratios and 95% confidence intervals for the primary outcome associated with baseline measurements of each adiposity marker.
Objectives The goal of this study was to determine if biomarkers of subclinical myocardial injury and hemodynamic stress identify asymptomatic individuals with left ventricular hypertrophy (LVH) at ...higher risk for heart failure (HF) and death. Background The interaction between LVH, low but detectable cardiac troponin T (cTnT), and elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) on cardiovascular (CV) outcomes in the general population is unknown. Methods Participants in the Dallas Heart Study without clinical HF, LV dysfunction, or chronic kidney disease underwent measurement of LV mass by magnetic resonance imaging (MRI), cTnT by highly sensitive assay, and NT-proBNP analysis (n = 2,413). Subjects were stratified according to LVH and by detectable cTnT (≥3 pg/ml) and increased NT-proBNP (>75th age- and sex-specific percentile) levels. For each analysis, participants were categorized into groups based on the presence (+) or absence (–) of LVH and biomarker levels above (+) or below (–) the predefined threshold. Results Nine percent of participants were LVH+, 25% cTnT+, and 24% NT-proBNP+. Those LVH+ and cTnT+ and/or NT-proBNP+ (n = 144) were older and more likely to be male, with a greater risk factor burden and more severe LVH compared with those who were LVH+ biomarker– (p < 0.01 for each). The cumulative incidence of HF or CV death over 8 years among LVH+ cTnT+ was 21% versus 1% (LVH– cTnT–), 4% (LVH– cTnT+), and 6% (LVH+ cTnT–) (p < 0.0001). The interactions between LVH and cTnT (pinteraction = 0.0005) and LVH and NT-proBNP (pinteraction = 0.014) were highly significant. Individuals who were LVH+ and either cTnT+ or NT-proBNP+ remained at >4-fold higher risk for HF or CV death after multivariable adjustment for CV risk factors, renal function, and LV mass compared with those who were LVH– biomarker–. Conclusions Minimal elevations in biomarkers of subclinical cardiac injury and hemodynamic stress modify the association of LVH with adverse outcomes, identifying a malignant subphenotype of LVH with high risk for progression to HF and CV death.
Objectives The goal of this study was to investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort. Background Natriuretic peptides stimulate ...lipolysis, reduce weight gain, and promote adipocyte browning in animal models, but data are lacking in humans. Methods A total of 2,619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP); and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index. Results Median BNP and NT-proBNP levels in the study cohort (mean age 44 years; 56% women, 48% African Americans, 32% obese) were 3.0 and 28.1 pg/ml, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance, including lower visceral fat, liver fat, and homeostasis model assessment of insulin resistance index, and increased lower body fat and higher adiponectin (p < 0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral fat (beta coefficient = −0.08; p < 0.0001) and liver fat (beta coefficient = −0.14; p < 0.0001) and positively associated with lower body fat (beta coefficient = 0.07; p < 0.0001) independent of age, sex, race, and obesity status; findings were similar with BNP. Adjustment for body composition, homeostasis model assessment of insulin resistance index, circulating androgens, and adipocytokines did not attenuate the associations. Conclusions Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides.
Background Patients with an acute myocardial infarction (AMI) who have glucose abnormalities are at increased risk for death and adverse ischemic outcomes. The contemporary prevalence of glucose ...abnormalities among AMI patients in the United States, as determined by hemoglobin A1c (HbA1c), is unknown. Methods Patients hospitalized with AMI in a 24-site US AMI registry from 2005 to 2008 were examined for the presence of dysglycemia using HbA1c, which was analyzed at a core laboratory. Patients were categorized by American Diabetes Association guidelines as having diabetes (HbA1c ≥ 6.5%), prediabetes (HbA1c 5.7%-6.4%), or normoglycemia. Baseline demographic, clinical, and metabolic characteristics, as well as long-term all-cause mortality, were compared among groups. Results Among 2,853 patients with AMI, 1,083 (38%) had diabetes, of which 196 (18%) were newly diagnosed. There were an additional 887 patients (31%) with prediabetes and 883 patients (31%) who had normal glucose metabolism. Patients with metabolic abnormalities were older, were more frequently female, and had higher prevalence of cardiac and noncardiac comorbidities, including multivessel disease and left ventricular systolic dysfunction. Patients with increasing metabolic abnormalities had higher mortality over the 3 years after the AMI (8.6% in those with normoglycemia, 10.6% in prediabetes, 11.3% in newly diagnosed diabetes, and 20.3% in known diabetes; log rank P < .001). Conclusions In a large US AMI registry, we found that nearly 7 in 10 patients had dysglycemia, with 38% having diabetes and an additional 31% with prediabetes based on HbA1c levels. Over half of the patients who did not have a known diagnosis of diabetes at the time of admission had either newly diagnosed diabetes or prediabetes. Progressively greater severity of dysglycemia was also associated with incremental increase in long-term mortality. These data highlight the AMI hospitalization as a key opportunity to screen for glucose abnormalities so that appropriate interventions and patient education efforts can be implemented prior to discharge.
Abstract Background The effect of saxagliptin on cardiovascular outcomes according to different hemoglobin A1c (HbA1c) levels has not been described. Thus, we analyzed the SAVOR-TIMI 53 trial to ...compare the cardiovascular effects of saxagliptin vs placebo according to baseline HbA1c. Methods A total of 16,492 patients with type 2 diabetes (HbA1c 6.5%-12.0% in the 6 months before randomization) and either a history of established cardiovascular disease or multiple risk factors for atherosclerosis were randomized to saxagliptin or placebo in addition to usual care. Patients were followed for a median of 2.1 years. The primary endpoint was cardiovascular death, myocardial infarction, or ischemic stroke. Results Patients were stratified by HbA1c at randomization into the following prespecified groups: <7%, 7%-<8%, 8%-<9%, and ≥9%. Baseline HbA1c ≥7% was associated with increased risk of cardiovascular death, myocardial infarction, or ischemic stroke (adjusted hazard ratio HRadj 1.35; 95% confidence interval CI, 1.17-1.58) but not hospitalization for heart failure (HRadj 1.09; 95% CI, 0.88-1.36). Saxagliptin neither increased nor decreased the risk of cardiovascular death, myocardial infarction, or ischemic stroke in patients with HbA1c <7% (HR 1.01; 95% CI, 0.78-1.31), 7%-<8% (HR 0.98; 95% CI, 0.80-1.20), 8%-<9% (HR 1.09; 95% CI, 0.85-1.39), ≥9% (HR 0.95; 95% CI, 0.77-1.18) ( P -interaction = .89). Conclusions Baseline HbA1c is associated with increased risk of macrovascular events but not hospitalization for heart failure. There was no heterogeneity in the effect of saxagliptin on cardiovascular events by baseline HbA1c, with cardiovascular death, myocardial infarction, or ischemic stroke neither increased nor decreased across the spectrum of baseline HbA1c values.
Background Patients with diabetes mellitus (DM) experience higher rates of in-stent restenosis and greater benefit from drug-eluting stents implant at the time of percutaneous coronary intervention ...(PCI), necessitating prolonged dual anti-platelet therapy (DAPT). While DAPT reduces risk of ischemic events post-PCI, it also increases risk of bleeding. Whether bleeding rates differ among patients with and without DM, receiving long-term DAPT is unknown. Methods Among patients who underwent PCI and were maintained on DAPT for 1 year in a multicenter US registry, we assessed patient-reported bleeding over one year following PCI in patients with and without DM. Multivariable, hierarchical Poisson regression was used to evaluate the association of DM with bleeding during follow-up. Results Among 2334 PCI patients from 10 US hospitals (mean age 64, 54% ACS), 32.6% had DM. In unadjusted analyses, patients with DM had fewer bleeding events over the year following PCI (DM vs no DM: BARC = 1: 78.0% vs 87.7%, P < .001; BARC ≥2: 4.3% vs 5.3%, P = .33). Following adjustment, patients with (vs without DM) had a lower risk of BARC ≥1 bleeding during follow-up (relative risk RR 0.89, 95% CI 0.83–0.96). This decreased bleeding risk persisted after removing bruising from the endpoint definition. Conclusions In a real-world PCI registry, patients with DM experienced lower risk of bleeding risk on DAPT. As patients with DM also derive greater ischemic benefit from drug-eluting stents, which requires prolonged DAPT, our findings suggest that the balance between benefit and risk of this therapeutic approach may be even more favorable in patients with DM than previously considered.
A Test in Context Gore, M. Odette, MD, MSCS; McGuire, Darren K., MD, MHSc
Journal of the American College of Cardiology,
12/2016, Letnik:
68, Številka:
22
Journal Article
Recenzirano
Odprti dostop
Abstract Measurement of glycated hemoglobin (HbA1c ), the most widely accepted indicator of long-term glycemic exposure, is central for the diagnosis and management of diabetes mellitus. Levels of ...HbA1c track epidemiologically with diabetic complications, and glycemic control, as reflected by HbA1c reduction, results in decreased risk of microvascular complications, including diabetic kidney disease, neuropathy, and retinopathy. The relationship between HbA1c reduction and cardiovascular disease prevention in patients with diabetes is more complex, with data from large randomized trials published over the past decade providing clear evidence that lowering of HbA1c per se is an inadequate marker for a therapeutic regimen’s impact on cardiovascular outcomes and patient survival. Recent revisions in professional society guidelines moved away from uniform recommendations and toward a more nuanced, patient-centered approach to HbA1c therapeutic targets. The context and key evidence underpinning these recent changes are discussed in this paper, alongside a brief overview of HbA1c contemporary assays and their limitations.
Background Physical activity (PA) participation differs by ethnicity, but contributing factors and cardiovascular (CV) outcomes related to these disparities are not well understood. We determined ...whether health beliefs regarding the benefit of PA contribute to ethnic differences in participation and assessed how these differences impact CV mortality. Methods The Dallas Heart Study is a longitudinal study of CV health. We assessed PA participation and health perceptions by questionnaire among 3,018 African American, Hispanic, and white men and women at baseline visit (2000-2002). Participant mortality was obtained through 2008 using the National Death Index. Results African Americans (odds ratio 0.65, 95% CI 0.53-0.80) and Hispanics (odds ratio 0.34, 95% CI 0.26-0.45) were less likely to be physically active compared with whites even after accounting for income, educational status, age, sex, body mass index, diabetes, hypertension, and hyperlipidemia. Beliefs regarding the benefits of PA did not contribute to this disparity, as >94% of individuals felt PA was effective in preventing a heart attack across ethnicity. Physical activity participation was associated with a lower risk of all-cause mortality (hazard ratio HR 0.66, 95% CI 0.46-0.93) and CV disease death (HR 0.56, 95% CI 0.32-0.97) in multivariable adjusted models. Similar results were seen when restricting to African Americans (CV disease death, HR 0.57, 95% CI 0.31-1.05). Conclusions Ethnic minorities reported less PA participation, and lack of PA was associated with higher CV mortality overall and among African Americans. Health perception regarding the benefits of PA did not contribute to this difference, indicating there are other ethnic-specific factors contributing to physical inactivity that require future study.
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