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Concept: Angina pectoris

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Background Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease. The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown. Methods Using a polygenic score of DNA sequence polymorphisms, we quantified genetic risk for coronary artery disease in three prospective cohorts - 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women’s Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) - and in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors: no current smoking, no obesity, regular physical activity, and a healthy diet. Results The relative risk of incident coronary events was 91% higher among participants at high genetic risk (top quintile of polygenic scores) than among those at low genetic risk (bottom quintile of polygenic scores) (hazard ratio, 1.91; 95% confidence interval [CI], 1.75 to 2.09). A favorable lifestyle (defined as at least three of the four healthy lifestyle factors) was associated with a substantially lower risk of coronary events than an unfavorable lifestyle (defined as no or only one healthy lifestyle factor), regardless of the genetic risk category. Among participants at high genetic risk, a favorable lifestyle was associated with a 46% lower relative risk of coronary events than an unfavorable lifestyle (hazard ratio, 0.54; 95% CI, 0.47 to 0.63). This finding corresponded to a reduction in the standardized 10-year incidence of coronary events from 10.7% for an unfavorable lifestyle to 5.1% for a favorable lifestyle in ARIC, from 4.6% to 2.0% in WGHS, and from 8.2% to 5.3% in MDCS. In the BioImage Study, a favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category. Conclusions Across four studies involving 55,685 participants, genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. Among participants at high genetic risk, a favorable lifestyle was associated with a nearly 50% lower relative risk of coronary artery disease than was an unfavorable lifestyle. (Funded by the National Institutes of Health and others.).

Concepts: Genetics, Epidemiology, Nutrition, Atherosclerosis, Angina pectoris, Coronary artery disease, Atheroma, Artery

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Objectives To investigate the association between alcohol consumption and cardiovascular disease at higher resolution by examining the initial lifetime presentation of 12 cardiac, cerebrovascular, abdominal, or peripheral vascular diseases among five categories of consumption.Design Population based cohort study of linked electronic health records covering primary care, hospital admissions, and mortality in 1997-2010 (median follow-up six years).Setting CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records).Participants 1 937 360 adults (51% women), aged ≥30 who were free from cardiovascular disease at baseline.Main outcome measures 12 common symptomatic manifestations of cardiovascular disease, including chronic stable angina, unstable angina, acute myocardial infarction, unheralded coronary heart disease death, heart failure, sudden coronary death/cardiac arrest, transient ischaemic attack, ischaemic stroke, intracerebral and subarachnoid haemorrhage, peripheral arterial disease, and abdominal aortic aneurysm.Results 114 859 individuals received an incident cardiovascular diagnosis during follow-up. Non-drinking was associated with an increased risk of unstable angina (hazard ratio 1.33, 95% confidence interval 1.21 to 1.45), myocardial infarction (1.32, 1.24 to1.41), unheralded coronary death (1.56, 1.38 to 1.76), heart failure (1.24, 1.11 to 1.38), ischaemic stroke (1.12, 1.01 to 1.24), peripheral arterial disease (1.22, 1.13 to 1.32), and abdominal aortic aneurysm (1.32, 1.17 to 1.49) compared with moderate drinking (consumption within contemporaneous UK weekly/daily guidelines of 21/3 and 14/2 units for men and women, respectively). Heavy drinking (exceeding guidelines) conferred an increased risk of presenting with unheralded coronary death (1.21, 1.08 to 1.35), heart failure (1.22, 1.08 to 1.37), cardiac arrest (1.50, 1.26 to 1.77), transient ischaemic attack (1.11, 1.02 to 1.37), ischaemic stroke (1.33, 1.09 to 1.63), intracerebral haemorrhage (1.37, 1.16 to 1.62), and peripheral arterial disease (1.35; 1.23 to 1.48), but a lower risk of myocardial infarction (0.88, 0.79 to 1.00) or stable angina (0.93, 0.86 to 1.00).Conclusions Heterogeneous associations exist between level of alcohol consumption and the initial presentation of cardiovascular diseases. This has implications for counselling patients, public health communication, and clinical research, suggesting a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary.Registration clinicaltrails.gov (NCT01864031).

Concepts: Myocardial infarction, Atherosclerosis, Angina pectoris, Cardiology, Heart, Cardiovascular disease, Stroke, Cardiovascular diseases

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Background To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome. Methods We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results A total of 5380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P<0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, -0.36 percentage points; P<0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo. Conclusions Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo. (Funded by Takeda Development Center Americas; EXAMINE ClinicalTrials.gov number, NCT00968708 .).

Concepts: Myocardial infarction, Atherosclerosis, Hypertension, Angina pectoris, Diabetes mellitus, Obesity, Cardiovascular disease, Acute coronary syndrome

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Background Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain. Methods After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. Results Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P=0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood. Conclusions Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE ClinicalTrials.gov number, NCT00738179 ; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370 .).

Concepts: Myocardial infarction, Atherosclerosis, Angina pectoris, Cardiovascular disease, Sleep, Sleep apnea, Obstructive sleep apnea, Cardiovascular diseases

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Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.

Concepts: Myocardial infarction, Atherosclerosis, Angina pectoris, Heart, The Canon of Medicine, Cardiovascular disease, Clopidogrel, Acute coronary syndrome

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BACKGROUND: Type VI dual left anterior descending artery (LAD) is a rare coronary anomaly, the first case of which has recently been described. This is the first report of type VI dual LAD anomaly in which the patient presented with non-ST-segment elevation myocardial infarction and percutaneous coronary intervention was performed in the anomalously originating LAD. CASE PRESENTATION: A 52-year-old man with diabetes, hypertension and hyperlipidemia presented with chest pain without ST elevation on EKG, although the patient’s troponin I level was elevated. Coronary angiography revealed a short LAD originating from the left main coronary artery and a long LAD originating from the proximal portion of the right coronary artery (RCA). Three-dimensional reconstruction of computed tomography of images revealed that the long LAD originated from the proximal RCA and coursed between the right ventricular outflow tract (RVOT) and the aortic root before entering the mid anterior interventricular groove. The high take-off RCA originated underneath the RVOT, pointing downwards and forming an acute angle with the proximal portion of the long LAD. The anomalous long LAD displayed significant stenosis. We performed successful percutaneous coronary intervention (PCI) in the anomalous artery. CONCLUSION: With accurate understanding of the coronary anatomy and appropriate hardware selection, successful PCI can be performed in the in the long LAD in patients with type VI dual LAD anomaly.

Concepts: Myocardial infarction, Atherosclerosis, Angina pectoris, Cardiology, Heart, Atheroma, Cardiovascular system, Left coronary artery

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Ischemic heart disease is a complex disease process caused by the development of coronary atherosclerosis, with downstream effects on the left ventricular myocardium. It is characterized by a long preclinical phase, abrupt development of myocardial infarction, and more chronic disease states such as stable angina and ischemic cardiomyopathy. Recent advances in computed tomography (CT) and cardiac magnetic resonance (CMR) now allow detailed imaging of each of these different phases of the disease, potentially allowing ischemic heart disease to be tracked during a patient’s lifetime. In particular, CT has emerged as the noninvasive modality of choice for imaging the coronary arteries, whereas CMR offers detailed assessments of myocardial perfusion, viability, and function. The clinical utility of these techniques is increasingly being supported by robust randomized controlled trial data, although the widespread adoption of cardiac CT and CMR will require further evidence of clinical efficacy and cost effectiveness.

Concepts: Myocardial infarction, Atherosclerosis, Angina pectoris, Cardiology, Heart, Atheroma, Artery, Coronary circulation

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INTRODUCTION There is no research that evaluated the tendency to reduce the traditional cardiovascular risk in patients with different values of coronary artery calcium score (CACS). The aim of the study was to evaluate the influence of the CACS examination for the reduction of the global cardiovascular risk. PATIENTS AND METHODS Research was conducted as prospective single center study. 180 subjects (aged 58.8) were included in the trial. Calcifications in computed tomography were calculated using the Agatston scale and “2DVScore with Color” semiautomatic presets by 2 experts. The selected cardiovascular risk factors were analyzed along with clinical procedures. RESULTS Invasive coronary angiography was performed on 60 patients (33.2%). Among these, the invasive examination did not show significant changes in the coronaries of 26 patients (43.3%), while in the other 26 patients (43.3%), coronary angioplasty (stents) were performed. Qualification for cardiac surgery without stents implantation was taken for eight subjects (13.3%). CABG procedures were performed exclusively in group III who had a CACS≥400AU; while angioplasty was performed 10 times more frequently in group III as compared to group II. A significant correlation between the CACS and cardiovascular risks was observed related to age, weight, systolic and diastolic blood pressure.  CONCLUSIONS The CACS results let to invasive coronary angioplasty to be performed in selected patients, or in some cases to qualify patients for coronary artery bypass grafts. This can strengthen the role of CACS as support for classic CVR risk evaluation. Additional continuing education about the role of the CACS should be implemented.

Concepts: Myocardial infarction, Atherosclerosis, Angina pectoris, Cardiology, Heart, Atheroma, Blood pressure, Coronary artery bypass surgery

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Background Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. Methods We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. Results The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. Conclusions When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878 .).

Concepts: Cholesterol, Myocardial infarction, Atherosclerosis, Angina pectoris, Cardiovascular disease, Low-density lipoprotein, Statin, Atheroma

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Prolonged QRS duration is a predictor of poor prognosis in patients with coronary artery disease. The association between the duration of QRS and myocardial reperfusion is not very well understood. Our aim was to assess the relationship between the measurements of QRS duration and myocardial blush grade (MBG) in patients with ST elevation myocardial infarction (STEMI) who were treated with a primary percutaneous intervention.

Concepts: Myocardial infarction, Atherosclerosis, Angina pectoris, Coronary artery disease, Heart, Percutaneous coronary intervention, Atheroma, Artery