Major Coronary Artery Disease Risk Research Articles

LncRNA CDKN2B-AS1 regulates collagen expression

The long noncoding RNA CDKN2B-AS1 harbors a major coronary artery disease risk haplotype, which is also associated with progressive forms of the oral inflammatory disease periodontitis as well as myocardial infarction (MI). Despite extensive research, there is currently no broad consensus on the function of CDKN2B-AS1 that would explain a common molecular role of this lncRNA in these diseases. Our aim was to investigate the role of CDKN2B-AS1 in gingival cells to better understand the molecular mechanisms underlying the increased risk of progressive periodontitis. We downregulated CDKN2B-AS1 transcript levels in primary gingival fibroblasts with LNA GapmeRs. Following RNA-sequencing, we performed differential expression, gene set enrichment analyses and Western Blotting. Putative causal alleles were searched by analyzing associated DNA sequence variants for changes of predicted transcription factor binding sites. We functionally characterized putative functional alleles using luciferase-reporter and antibody electrophoretic mobility shift assays in gingival fibroblasts and HeLa cells. Of all gene sets analysed, collagen biosynthesis was most significantly upregulated (Padj=9.7 × 10− 5 (AUC > 0.65) with the CAD and MI risk gene COL4A1 showing strongest upregulation of the enriched gene sets (Fold change = 12.13, Padj = 4.9 × 10− 25). The inflammatory “TNFA signaling via NFKB” gene set was downregulated the most (Padj=1 × 10− 5 (AUC = 0.60). On the single gene level, CAPNS2, involved in extracellular matrix organization, was the top upregulated protein coding gene (Fold change = 48.5, P < 9 × 10− 24). The risk variant rs10757278 altered a binding site of the pathogen responsive transcription factor STAT1 (P = 5.8 × 10− 6). rs10757278-G allele reduced STAT1 binding 14.4% and rs10757278-A decreased luciferase activity in gingival fibroblasts 41.2% (P = 0.0056), corresponding with GTEx data. CDKN2B-AS1 represses collagen gene expression in gingival fibroblasts. Dysregulated collagen biosynthesis through allele-specific CDKN2B-AS1 expression in response to inflammatory factors may affect collagen synthesis, and in consequence tissue barrier and atherosclerotic plaque stability.

Acute Myocardial Infarction in Women, a Study on Risk Factors, Angiographic Features and Outcomes.

Women with acute coronary syndrome are more likely to have cardiovascular disease risk factors and atypical symptoms as compared to men. In Nepal, there is a rising trend of Coronary Artery Disease and myocardial infarction in women. However, research on acute myocardial infarction in women is lacking. The aim of this study was to study the cardiac risk factors, clinical features, angiographic features, and outcome of acute myocardial infarction in Nepalese women admitted to Hospital. This was a cross sectional study done at Shahid Gangalal National Heart Center Kathmandu from September 2016 to March 2017. Female patients admitted with a diagnosis of acute ST-segment elevation myocardial infarction or non-ST segment elevation myocardial infarction, who fulfilled the inclusion criteria were included in the study. The details of the patients, demographic profile, major clinical symptoms, major coronary artery disease risk factors, angiographic features and outcomes were recorded and assessed during the study period. Coronary angiography was done in 112 patients out of 178 patients. Out of 178 patients, 85.95 % had ST-segment elevation myocardial infarction and 14.05% had non-ST segment elevation myocardial infarction. The mean patient age was 62.53 ± 12.1. 26.4% patients were of age less than 55 years. Major risk factors were central obesity (94.61%), dyslipidemia due to low HDL (78.65%). hypertension (54.49%), smoking (54.49%) and type 2 diabetes (34.83%). The most common atypical symptoms were shortness of breath (35.39 %,) , nausea and vomiting (23. 6%) and epigastric pain (6.74%), Single vessel disease was found in 36%; double vessel disease in 26.3% and triple vessel disease in 28.9% of patients. The primary outcome of in- hospital mortality was 3.37 %. Our study showed that significant number of females had Coronary Artery Disease at early age. Among women with myocardial infarction in Nepal, obesity due to high waist to hip ratio was the most common risk factor followed by dyslipidemia due to low high density lipoproteins, smoking, hypertension, and diabetes. Atypical symptoms were also common findings. Single vessel disease was the most common lesion and left anterior descending artery was the most commonly involved vessel. Mortality was seen in ST-segment elevation myocardial infarction patients only.

Association Between Major Coronary Artery Disease Risk Factors in The City of Cape Town Firefighter and Rescue Service

Background:Many CAD risk factors occur concurrently, increasing the odds of the development of other risk factors, which is particularly seen in male and older firefighters.Objective:The purpose of this study was to determine the association and odds ratios between the various CAD risk factors in firefighters.Methods:This study used a quantitative, cross-sectional and correlational design. A total of 124 full-time firefighters, males and females, were conveniently recruited from the City of Cape Town Fire and Rescue Service. A researcher generated questionnaire was used to collect participant sociodemographic information, and all research procedures were conducted according to the ACSM guidelines. The study took place between September and November 2019.Results:There were significant associations between hypertension and age [χ2(1) = 18.0, p &lt; 0.001, OR = 6.3 (95% CI: 2.6, 15.5)], hypertension and obesity [χ2(1) = 7.9, p = 0.005, OR = 3.0 (95% CI: 1.4, 6.6)], hypertension and diabetes [χ2(1) = 5.1, p = 0.040, OR = 4.0 (95% CI: 1.1, 14.8)], and hypertension and dyslipidaemia [χ2(1) = 8.5, p = 0.004, OR = 3.1 (95% CI: 1.4, 6.7)], family history and central obesity [χ2(1) = 3.9, p = 0.04, OR = 2.4 (95% CI: 0.9, 5.8)], and family history and central obesity [χ2(1) = 3.9, p = 0.04, OR = 2.4 (95% CI: 0.9, 5.8)].Conclusion:Increased age, central obesity, hypertension and dyslipidaemia increased the odds of developing other major CAD risk factors, which was predominantly apparent in male firefighters of mixed ethnicity. The City of Cape Town Fire and Rescue Service should emphasize the mitigation of these major CAD risk factors through education and behavioural modification, especially as male firefighters aged.

A comparative study of efficacy of atorvastatin alone and its combination with fenofibrate on lipid profile in type 2 diabetes mellitus patients with hyperlipidemia.

Mixed dyslipidemia is characterized by increased low-density lipoprotein cholesterol (LDL-C) elevated triglycerides (TGs) and decrease high-density lipoprotein cholesterol (HDL-C). It is more common in diabetes and is associated with an increased risk of coronary artery disease. Monotherapy with statins or fibrates may not effectively control all lipid parameters. The atorvastatin-fenofibrate combination has been shown to have highly beneficial effect on lipid parameters in type 2 diabetes associated with combined hyperlipidemia (CHL). In an open-label study, we evaluated the efficacy of atorvastatin alone and in combination with fenofibrate in 60 types 2 diabetes mellitus patients associated with hyperlipidemia. Patients were randomly assigned to receive atorvastatin 10 mg (Group 1) or combination of atorvastatin 10 mg and fenofibrate 145 mg (Group 2) once daily for 12 weeks. The effect of drugs on lipid profile was evaluated before and after treatment. After 12 weeks, the reduction in total cholesterol (TC), TGs, LDL-C, VLDL-C was 28%, 20%, 37% and 20% in Group 1 (P < 0.001 for all) as compared with 31%, 39%, 33% and 40% in Group 2 (P < 0.001 for all). There was insignificant rise in HDL-C in Group 1 (P = 0.71) and insignificant decrease in HDL-C (P = 0.70) in Group 2. During the combination therapy, the decrease in TC, TGs and VLDL-C was greater than atorvastatin alone. The combination of atorvastatin with fenofibrate in type 2 diabetes patients with CHL may have a favorable effect on some major coronary artery disease risk factors.

Modifications of Coronary Risk Factors

In addition to the revascularization and glycemic management interventions assigned at random, the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) design includes the uniform control of major coronary artery disease risk factors, including dyslipidemia, hypertension, smoking, central obesity, and sedentary lifestyle. Target levels for risk factors were adjusted throughout the trial to comply with changes in recommended clinical practice guidelines. At present, the goals are low-density lipoprotein cholesterol <2.59 mmol/L (<100 mg/dL) with an optional goal of <1.81 mmol/L (<70 mg/dL); plasma triglyceride level <1.70 mmol/L (<150 mg/dL); blood pressure level <130 mm Hg systolic and <80 mm Hg diastolic; and smoking cessation treatment for all active smokers. Algorithms were developed for the pharmacologic management of dyslipidemia and hypertension. Dietary prescriptions for the management of glycemia, plasma lipid profiles, and blood pressure levels were adapted from existing clinical practice guidelines. Patients with a body mass index >25 were prescribed moderate caloric restriction; after the trial was under way, a lifestyle weight-management program was instituted. All patients were formally prescribed both endurance and resistance/flexibility exercises, individually adapted to their level of disability and fitness. Pedometers were distributed as a biofeedback strategy. Strategies to achieve the goals for risk factors were designed by BARI 2D working groups (lipid, cardiovascular and hypertension, and nonpharmacologic intervention) and the ongoing implementation of the strategies is monitored by lipid, hypertension, and lifestyle intervention management centers.

Cholesterol Primer for Health Professionals

As research continues in the field of coronary artery disease, more information is revealed about various etiological factors. Emerging lipoprotein risk factors have been identified and are now starting to surface as instrumental in the cause and prevention of coronary artery disease. In order to conduct comprehensive cholesterol screening programs and counseling sessions a health professional must have a thorough understanding of lipid metabolism. Recent changes in cholesterol guidelines make it necessary to have a review that addresses the specifics of lipid management. A health professional needs an appropriate knowledge base to be able to understand a major coronary artery disease risk factor and thereby more effectively educate the public about lipid management and coronary artery disease risk reduction. Therefore, the purpose of this article is to review the role of cholesterol in both normal physiological functioning and disease causation and to examine the research concerning new emerging cholesterol risk factors.

Safety and Efficacy of Long-Term Statin-Fibrate Combinations in Patients With Refractory Familial Combined Hyperlipidemia

No monotherapy is able to tackle effectively all atherogenic features of familial combined hyperlipidemia: high low-density lipoprotein (LDL) cholesterol, triglycerides (TG), and plasma fibrinogen, as well as low high-density lipoprotein (HDL) cholesterol. The present study investigated the safety and efficacy of combined pravastatin or simvastatin with gemfibrozil or ciprofibrate treatment on total cholesterol, LDL, TG, plasma fibrinogen, and apoproteins B and A-I in patients with refractory familial combined hyperlipidemia, with or without coronary artery disease. From the initial 420 patients included in the study, 389 (294 men and 95 women, mean age 51 years [range 30 to 65]) completed the study. These patients were followed for a mean period of 29 months (1 year [n = 107], 2 years [n = 102], 3 years [n = 95], and 4 years [n = 85]). Patients given a hypolipidemic diet were randomly assigned to pravastatin + gemfibrozil (n = 135, 20 and 1,200 mg/day, respectively), simvastatin + gemfibrozil (n = 130, 20 and 1,200 mg), or simvastatin + ciprofibrate (n = 124, 20 and 100 mg). Lipid parameters, apoproteins B and A-I, and plasma fibrinogen were assessed every 3 months. Physical and laboratory investigations for adverse effects were performed every month for the first 3 months and every 3 months thereafter. No patient exhibited myopathy or rhabdomyolysis. Five patients (1.3%) were withdrawn from the study because of high transaminases (more than threefold the upper normal limit). Five nonfatal coronary artery disease events were recorded. All 3 combination treatments were more effective in normalizing lipid profile than any monotherapy in the past. Simvastatin + ciprofibrate was more effective than pravastatin + gemfibrozil in reducing LDL, TG, and plasma fibrinogen levels. Simvastatin + gemfibrozil increased HDL levels more than the other 2. The apoprotein B decrease was analogous to the LDL reduction by all combinations, whereas apoprotein A-I was increased more with simvastatin + gemfibrozil. The data suggest that the statin-fibrate combinations used in the study are safe and have a favorable effect on all major coronary artery disease risk factors in patients with refractory familial combined hyperlipidemia with or without coronary artery disease. Early detection of the rare drug-induced reversible hepatotoxicity calls for close monitoring of patients.

Prevalence and effects of nonpharmacologic treatment of "isolated" low-HDL cholesterol in patients with coronary artery disease.

To determine the the prevalence of isolated low high-density lipoprotein cholesterol and its response to hygienic therapy in coronary patients after major cardiac events. Data before and after phase II cardiac rehabilitation and exercise training were assessed in 275 consecutive patients from two institutions. All patients had known coronary artery disease and underwent a 12-week program of aggressive hygienic therapy. The prevalence of isolated low high-density lipoprotein cholesterol in this cohort was determined and its response to vigorous nonpharmacologic therapy was assessed and compared with that of other coronary patients undergoing similar therapy. At baseline, 113 (41%) had low high-density lipoprotein cholesterol, including 70 (25%) with isolated low high-density lipoprotein cholesterol. In contrast, 147 (53%) had "high-risk" low-density lipoprotein-cholesterol > or = 130 mg/dL. In the subgroup with isolated low high-density lipoprotein cholesterol, improvements occurred in body mass index, metabolic equivalents, high-density lipoprotein cholesterol, and low-density lipoprotein/high-density lipoprotein cholesterol. Compared with 205 patients without isolated low high-density lipoprotein cholesterol, this subgroup had much greater improvements in high-density lipoprotein cholesterol (+17% versus +2%; P < .001) and low-density lipoprotein/high-density lipoprotein cholesterol (-11% versus -6%; P < .02), with similar improvements in most other major coronary artery disease risk factors. These results suggest that isolated low high-density lipoprotein cholesterol is prevalent in patients with coronary artery disease and is sensitive to aggressive hygienic interventions.