Composite Of Nonfatal Myocardial Infarction Research Articles

South Asian ethnicity as a risk factor for major adverse cardiovascular events after renal transplantation.

South Asians (SAs) comprise 25% of all Canadian visible minorities. SAs constitute a group at high risk for cardiovascular disease in the general population, but the risk in SA kidney transplant recipients has never been studied. In a cohort study of 864 kidney recipients transplanted from 1998 to 2007 and followed to June 2009, we identified risk factors including ethnicity associated with major cardiac events (MACEs, a composite of nonfatal myocardial infarction, coronary intervention, and cardiac death) within and beyond 3 months after transplant. Kaplan-Meier methodology and multivariate Cox regression analysis were used to determine risk factors for MACEs. There was no difference among SAs (n = 139), whites (n = 550), blacks (n = 65), or East Asians (n = 110) in baseline risk, including pre-existing cardiac disease. Post-transplant MACE rate in SAs was 4.4/100 patient-years compared with 1.31, 1.16, and 1.61/100 patient-years in whites, blacks, and East Asians, respectively (P < 0.0001 versus each). SA ethnicity independently predicted MACEs along with age, male gender, diabetes, systolic BP, and prior cardiac disease. SAs also experienced more MACEs within 3 months after transplant compared with whites (P < 0.0001), blacks (P = 0.04), and East Asians (P = 0.006). However, graft and patient survival was similar to other groups. SA ethnicity is an independent risk factor for post-transplant cardiac events. Further study of this high-risk group is warranted.

CHARACTERISTIC FEATURES OF PROGRESSIVE CARDIOVASCULAR DISEASE IN TYPE 2 DIABETIC PATIENTS WITHOUT HYPERTENSION-10 YEARS FOLLOW-UP: PP.17.119

Aim: Incidence of cardiovascular disease (CVD) in diabetes is related to not only glucose levels, but also multiple risk factors. Hypertension is a common comorbidity in patients with diabetes, and greatly increases the risk of CVD. To know characteristic features of progressive CVD in diabetes, we investigate relationship between incidence of CVD and risk factors and left ventricular (LV) function at baseline and progression of hypertension in type 2 diabetic patients without hypertension with 10-year follow-up. Subjects and Methods: In 1998 and 1999, 97 type 2 diabetic patients without hypertension who did not have both overt cardiac disease and macro-albuminuria were enrolled. Eighty-four patients (male 54, age 56 (8) years (mean (SD)), BMI 23.0 (2.7) kg/m2) were completed 10-year follow-up. Clinical characteristics and echocardiography was performed at baseline. LV internal diameter was measured by M-mode echocardiography, and fractional shortening (FS) and LV mass were also calculated. LV systolic function was assessed by FS, and LV diastolic function was assessed by the ratio between the peak diastolic velocity and the peak atrial systolic velocity (E/A) and isovolumic relaxation time (IVRT) with Doppler examination. Hypertension was defined that patients with 140 and/or 85 mmHg and more, or use of antihypertensive medications. The primary outcome was a composite of nonfatal myocardial infarction (MI), nonfatal stroke, or death from cardiovascular causes. Results: During 10-year follow-up, 14 patients (17%) had CVD events (8 patients had nonfatal MI, 4 angina pectoris, 1 heart failure, and 1nonfatal stroke.)(CVD group), and 4 patients died of cancer and leukemia, and 66 patients did not have any cardiovascular diseases (N group). CVD group had older age (60 (6) vs 55 (6) years, p < 0.05), elevated systolic blood pressure (130 (10) vs 121 (11) mmHg, p < 0.01), higher LDL cholesterol level (141 (20) vs 123 (36) mg/dl, p < 0.05), and higher presence of retinopathy (64 vs 35 %, p < 0.05) at baseline than N group. During 10 years, 54% of CVD group had newly diagnosed hypertension as compared to 23% in N group, but there were not significant differences between CVD and progression of hypertension. For LV function, CVD group had decreased LV diastolic function as compared to N group (IVRT 78.5 (16.3) vs 70.6 (10.7) ms, p < 0.05). In logistic regression analysis, independent risk factors for CVD were presence of retinopathy (3.059 (1.309–7.153); OR (95% CI), p <0.005), extended IVRT (1.050 (0.999–1.109), p = 0.05), systolic blood pressure at baseline (1.062 (0.998–1.113), p = 0.059). Conclusions: During 10-year follow-up, 17% of type 2 diabetic patients without hypertension had CVD. It suggests that LV diastolic dysfunction is a subclinical important factor for incidence of CVD, and to preserve lower blood pressure level may also be important to prevent CVD in type 2 diabetic patients.

Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial

Objective To investigate whether dietary supplementation with B vitamins or omega 3 fatty acids, or both, could prevent major cardiovascular events in patients with a history of ischaemic heart disease...

Coronary heart disease in moderately hypercholesterolemic, hypertensive black and non-black patients randomized to pravastatin versus usual care: The Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial (ALLHAT-LLT)

In previous analyses in ALLHAT, blacks had a significantly lower risk of coronary heart disease (CHD) in the pravastatin group compared to the usual care group, whereas non-blacks had no benefit from pravastatin. No previous statin trial has reported results separately in blacks. The study aimed to determine if apparent racial differences in CHD in ALLHAT are explained by differences in baseline characteristics, adherence during the trial, or achieved blood pressure and lipid lowering. This was a prespecified subgroup analysis of a randomized controlled trial. Hypertensive, moderately hypercholesterolemic participants were assigned to open-label pravastatin (40 mg/d) or usual care. The outcome was a composite of nonfatal myocardial infarction and fatal CHD. We performed intention-to-treat survival analyses using Cox proportional hazards models, adjusting for baseline covariates (age, sex, aspirin use, history of CHD and diabetes, and baseline hypertension treatment) and time-varying levels of blood pressure and total cholesterol. After adjustment for baseline characteristics, there remained a significant interaction between race and treatment group (P = .02). In stratified models, blacks in the pravastatin group had a 29% lower risk of CHD (hazard ratio [HR] 0.71, 95% CI 0.57-0.90, P = .005) compared to those in the usual care group, whereas non-blacks had no benefit (HR 1.00, 95% CI 0.85-1.19, P = .95). With further adjustment for achieved blood pressure and total cholesterol, the HR in blacks was 0.65 (95% CI 0.45-0.96, P = .03) and in non-blacks was 1.07 (95% CI 0.81-1.41, P = .65). Our results suggest that pravastatin is effective in preventing CHD in blacks.

CRP in Cardiovascular Disease

In primary prevention, traditional risk factors are a useful first step in determining who is at cardiovascular risk, however, it has been noted that a considerable number of those at risk cannot be identified on the basis of traditional risk factors alone. Among blood biomarkers, C-reactive protein (CRP), measured by high-sensitivity assays (hsCRP), has received widespread interest and a large database has been accumulated on its potential role as a predictor of cardiovascular risk, although observed associations between circulating CRP and coronary heart disease (CHD) are unlikely to be causal, as recently indicated by various Mendelian randomization studies. In a meta-analysis of 22 prospective studies, the multivariable adjusted, combined odds ratio for CRP to predict CHD, comparing extreme tertiles, was 1.58 (95% confidence interval, 1.48-1.68). Several recent studies showed a significant contribution of CRP to coronary risk prediction independent of the Framingham Risk Score, with better discrimination, calibration and improved, albeit modest reclassification of subjects at risk. To test the hypothesis whether or not subjects with normal low-density lipoprotein cholesterol but elevated CRP represent a population at increased risk that might benefit from statin treatment, the JUPITER trial randomized 17,802 apparently healthy persons to either 20 mg rosuvastatin daily or placebo. Rosuvastatin significantly reduced the incidence of major cardiovascular events. The rates of the primary endpoint (composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, revascularization, and confirmed death from cardiovascular causes) were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively. Relative risk reduction was 44%. CRP may have more accurately selected high-risk subjects due to its association with very many risk factors, thus representing an integrative marker of the total inflammatory burden of an individual. JUPITER has revitalized the discussion on CRP in clinical practice and will make it more difficult in the future to neglect the evidence built around CRP and cardiovascular risk.

Changing the Treatment Paradigm for Type 2 Diabetes

Based on the results of the U.K. Prospective Diabetes Study (UKPDS), “… treatment of type 2 diabetes [should] include aggressive efforts to lower blood glucose levels as close to normal as possible. …” This was the recommendation the American Diabetes Association promulgated based on the results of the UKPDS when published (1). The suggestion was soon adopted by official guidelines in every region of the world (2). They are generally consistent in recommending an A1C goal of <7.0%. However, the results of the UKPDS remained inconclusive with respect to cardiovascular (CV) complications because of a risk reduction that was only close to statistical significance (−16%, P = 0.052). In support of the UKPDS results, however, a recent meta-analysis of randomized trials in type 2 diabetes (3) calculated a 19% reduction in the incidence of any type of macrovascular event associated with improved long-term glycemic control. Moreover, a strong association between glycemic control and micro- and macrovascular disease has been highlighted in type 1 diabetic patients (4,5). Nevertheless, these results have been challenged by recent large-scale intervention trials. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial randomized >10,000 subjects with type 2 diabetes and vascular disease, or multiple CV risk factors, to an intensive treatment program targeting normal blood glucose values and A1C <6%, or a standard treatment program aiming at A1C between 7 and 7.9%. The intensive blood glucose arm was prematurely stopped because of excess mortality (hazard ratio [HR] 1.22, 95% CI 1.01–1.46; P = 0.04) and lack of significant reduction of primary outcome, i.e., a composite of nonfatal myocardial infarction, nonfatal stroke, or death from CV causes (HR 0.90, 0.78–1.04; P = 0.16) (6). After a median 5-year follow-up, the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE), …

Bleeding Increases the Risk of Ischemic Events in Patients With Peripheral Arterial Disease

Patients with peripheral arterial disease are at high risk of ischemic events and therefore are treated with antithrombotics. In patients with coronary artery disease or cerebrovascular disease, bleeding is related to the subsequent occurrence of ischemic events. Our objective was to assess whether this is also the case in patients with peripheral arterial disease. All patients from the Dutch Bypass and Oral Anticoagulants or Aspirin (BOA) Study, a multicenter randomized trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery, were included. The primary outcome event was the composite of nonfatal myocardial infarction, nonfatal ischemic stroke, major amputation, and cardiovascular death. To identify major bleeding as an independent predictor for ischemic events, crude and adjusted hazard ratios with 95% confidence intervals were calculated with multivariable Cox regression models. From 1995 until 1998, 2650 patients were included with 101 nonfatal major bleedings. During a mean follow-up of 14 months, the primary outcome event occurred in 218 patients; 22 events were preceded by a major bleeding. The mean time between major bleeding and the primary outcome event was 4 months. Major bleeding was associated with a 3-fold increased risk of subsequent ischemic events (crude hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.6; adjusted hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.7). In patients with peripheral arterial disease, as in patients with coronary artery disease or cerebrovascular disease, major bleeding was independently associated with major ischemic complications. Without compromising the benefits of antithrombotics, these findings call for caution relative to the risks of major bleeding.

Improving the Prognosis in Patients With Diabetes: What Will ADVANCE Tell Us?

The rising tide of diabetes fueled by an epidemic of obesity is worrisome, particularly in view of the anticipated increase in cardiovascular morbidity and mortality associated with such changes in the future. There is an urgent need to offset this predicted rise in cardiovascular events by improving the current understanding of the importance of the independent and net benefits of glycemic and blood-pressure control, and the use of multirisk interventions in patients with diabetes. Current knowledge about the benefits of various interventions is reviewed: glycemic control, blood pressure-lowering, lipid lowering, and others. Also, some of the unresolved questions relating to the optimal management of Type 2 diabetes are identified. The extent to which results of the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release (MR) Controlled Evaluation) will answer some of these questions is considered. ADVANCE is a large, multicenter, randomized controlled trial, and uses a factorial 2 × 2 design to determine the effects on macrovascular and microvascular outcomes of blood pressure-lowering (using an angiotensin-converting enzyme inhibitor and diuretic combination) and of intensive glucose control using a gliclazide MR-based regimen. 11,140 patients were randomized, and followed for 5.5 years for two primary outcomes: (1) a composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death, and (2) new or worsening nephropathy or microvascular eye disease. The ADVANCE trial is likely to provide generalizable data on the benefits of blood pressure-lowering, regardless of initial blood pressure and intensive glucose control beyond current glycemic targets, and may resolve current issues about the net benefits of the two interventions. Am J Hypertens 2007;20: 19S–22S © 2007 American Journal of Hypertension, Ltd.

Anxiety Worsens Prognosis in Patients With Coronary Artery Disease

This study examined the effect of anxiety on mortality and nonfatal myocardial infarction (MI) in patients with coronary artery disease (CAD). Inconsistent data exist regarding the impact of anxiety on the prognosis of patients with CAD. The authors conducted a prospective cohort study at an outpatient cardiology clinic of 516 patients with CAD (mean age 68 years at entry, 82% male) by administering the Kellner Symptom Questionnaire annually. The primary outcome was the composite of nonfatal MI or all-cause mortality. During an average follow-up of 3.4 years, we documented 44 nonfatal MIs and 19 deaths. A high cumulative anxiety score was associated with an increased risk of nonfatal MI or death. Comparing the highest to lowest tertile of anxiety score, the age-adjusted hazard ratio was 1.97 (95% confidence interval 1.03 to 3.78, p = 0.04). In a multivariate Cox model after adjusting for age, gender, education, marital status, smoking, hypertension, diabetes mellitus, previous MI, body mass index, and total cholesterol, each unit increase in the cumulative mean anxiety score was associated with increased risk of nonfatal MI or total mortality; the hazard ratio was 1.06 (95% confidence interval 1.01 to 1.12, p = 0.02). A high level of anxiety maintained after CAD diagnosis constitutes a strong risk of MI or death among patients with CAD.

Osteopontin, coronary calcification, and cardiovascular events: future diagnostic and therapeutic targets for disease prevention?The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.

This editorial refers to ‘Prognostic significance of plasma osteopontin levels in patients with chronic stable angina’† by P. Minoretti et al., on page 802 Minoretti et al. 1 describe the independent prognostic significance of plasma osteopontin (OPN). OPN was measured in baseline plasma samples from 799 patients with stable angina pectoris and angiographically documented coronary artery disease (CAD). Participants were prospectively followed for a median of 2.7 years. The primary study endpoint was a composite of non-fatal myocardial infarction and cardiovascular death. Age, number of diseased vessels, and treatment with statins were independent predictors of baseline plasma OPN levels. In univariate analysis, the log-transformed OPN level, levels of C-reactive protein, hypertension, and statin use were associated with future adverse events. Levels of OPN and C-reactive protein and hypertension remained independent predictors of adverse cardiovascular outcome in multivariable analysis. The study was limited to a patient population with angiographically documented stable CAD. Future studies in populations with subclinical disease (e.g. <50% angiographic stenosis or plaque by other imaging modalities) will be crucial to assess the prognostic value of OPN in primary disease prevention. OPN is a calcium-binding, phosphorylated glycoprotein, which was originally identified as a mediator involved in bone remodelling. However, subsequent studies demonstrated that OPN … *Corresponding author. Tel: +1 216 445 7579; fax: +1 216 445 6855. E-mail address : schoenp1{at}ccf.org

Prognostic significance of plasma osteopontin levels in patients with chronic stable angina

Levels of the secreted glycophosphoprotein osteopontin (OPN) have been associated with the presence and extent of coronary artery disease (CAD). The present study assessed the relationship between plasma OPN concentrations and prognosis in patients with chronic stable angina (CSA). OPN was measured in baseline plasma samples from 799 patients with stable angina pectoris and angiographically documented CAD. Participants were prospectively followed-up for a median of 2.7 years (maximum 4.1 years). The primary study endpoint was the composite of non-fatal myocardial infarction and death from cardiovascular causes. In the univariate Cox proportional hazard analysis, the log-transformed OPN level [hazard ratio (HR) 1.79, 95% CI 1.35-2.36, P < 0.001] was significantly related to adverse outcome. In addition, hypertension, levels of C-reactive protein, and statin use were associated with future adverse events. Levels of OPN (HR, 1.88; P < 0.001) and C-reactive protein (HR, 1.42; P = 0.003), as well as the presence of hypertension (HR, 2.39; P = 0.008) remained statistically significant, independent predictors of adverse cardiovascular outcome in a multivariable Cox proportional hazard analysis. Baseline levels of OPN are an independent predictor of future adverse cardiac events in patients with CSA and may be useful for risk stratification.

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Elevated serum neopterin predicts future adverse cardiac events in patients with chronic stable angina pectoris

Serum levels of neopterin, an immune modulator secreted by activated macrophages, are elevated in patients with acute coronary syndromes compared with stable angina patients and control subjects. In unstable angina, serum neopterin levels correlate with the presence of vulnerable coronary stenosis, multiple complex coronary lesions, and patient outcome. The present study assessed the prognostic significance of raised serum neopterin concentrations in patients with stable angina pectoris. We carried out a 1-year follow-up prospective study in 297 patients with chronic stable chest pain undergoing diagnostic coronary angiography. The primary study endpoint was the composite of non-fatal myocardial infarction, unstable angina, and cardiac death. Fifty-one patients (17.2%) had adverse coronary events during follow-up. Mean serum neopterin levels were significantly higher in patients with events compared with those without (P=0.02). On multiple regression analysis, neopterin levels (P=0.021), severity of coronary artery disease (P=0.009), and a history of previous myocardial infarction (P=0.001) were independent predictors of adverse events. Serum neopterin is an independent predictor of major adverse coronary events in patients with chronic stable angina pectoris. This marker of macrophage activation may be useful for risk stratification in patients with chronic stable angina.

Critical Commentary

Testosterone exerts some effects on the cardiovascular system that could be considered beneficial; some other effects may potentially increase the risk of cardiovascular (CV) events. Neither the long-term efficacy nor safety of testosterone treatment has been studied in an adequately-powered randomized trial.The Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) study is a randomized, double-blind, placebo-controlled, parallel group, non-inferiority, multicenter study. Eligible participants are men, 45 to 80 years, with serum testosterone concentration <300 ng/dL and hypogonadal symptoms, who have evidence pre-existing CV disease or increased risk of CV disease. Approximately 6,000 subjects will be randomized to either 1.62% transdermal testosterone gel or a matching placebo gel daily for an anticipated duration of up to 5 years. The primary outcome is CV safety defined by the major adverse CV event composite of nonfatal myocardial infarction, nonfatal stroke, or death due to CV causes. The trial will continue until at least 256 adjudicated major adverse CV event endpoints have occurred to assess whether the 95% (2-sided) upper confidence limit for a hazard ratio of 1.5 can be ruled out. Secondary endpoints include prostate safety defined as the incidence of adjudicated high grade prostate cancer and efficacy in domains of sexual function, bone fractures, depression, anemia, and diabetes.As of July 1, 2021, 5,076 subjects had been randomized.The TRAVERSE study will determine the CV safety and long-term efficacy of testosterone treatment in middle-aged and older men with hypogonadism with or at increased risk of CV disease.