Genetic polymorphisms as risk factors for coronary artery disease

The acute myocardial infarction is a multi factor disease, and various risk factors participate in its occurrence and progression. Recently, many investigators have paid their attention to the genetic polymorphisms as new risk factors for coronary artery disease. These include the polymorphisms or mutations of the gene which relates to hypertension, diabetes, the platelet function, the property of the blood vessel, the blood coagulation fibrinogenolysis system, and serum lipids. The tendency toward the occurrence and progression of coronary artery disease might be decided genetically by combining these genetic polymorphisms.     

Risk factors in the pathogenesis of coronary artery disease

In men, plaque rupture is strongly correlated with total cholesterol, and smoking is a predictor of acute thrombosis. In women younger than 50, plaque erosion correlates with smoking, whereas in women older than 50, thrombosis is secondary to plaque rupture and correlates with total cholesterol.     

Association between white blood cell count and risk factors of coronary artery disease

BACKGROUND: Epidemiologic studies have shown a correlation between white blood cell (WBC) count and risk of developing myocardial infarction. Aim of this study is to assess the association between WBC and the other risk factors of coronary heart disease in a southern Italian population. METHODS: Baseline data for the 1091 subjects (522 males and 569 females) enrolled in the "Montecorvino Rovella Project" were used to study factors associated with leukocytes. RESULTS: WBC count was significantly higher in smokers (8711.1 +/- 1892 cells/dl) than in ex-smokers (6720 +/- 1608 cells/dl) and in those who never smoked (6674 +/- 1608 cells/dl). By multiple linear regression analysis, WBC count showed a positive association with triglycerides (p < 0.01), cholesterol (p < 0.05) fasting glucose levels (p < 0.01) and diastolic blood pressure (p < 0.05). CONCLUSIONS: In this southern Italian population, elevated WBC count has been associated with other risk factors of coronary artery disease, particularly smoking, and has identified a high risk atherogenic profile. Even if the independency of the role of WBC is still under investigation, WBC count should be taken into account in establishing the coronary risk of apparently healthy people.     

Angiotensinogen and angiotensin-I converting enzyme gene polymorphisms and the risk of coronary artery disease in Chinese

We investigated extracts of timothy grass pollen from four seasons (1989, 1990, 1991, and 1994) by protein content, SDS-PAGE, immunoblot, RAST, RAST inhibition, and crossed immunoelectrophoresis. Extract of the pollen from 1991 showed the lowest yield in quantitative assays. SDS-PAGE, crossed immunoelectrophoresis, RAST, and RAST inhibition expressed approximately comparable patterns for all extracts except that from 1991. Obviously, the quality of grass pollens, as shown for some ragweed (Ambrosia elatior) pollens depend on year of collection. Our findings are partially in agreement with some earlier examinations of the quality of timothy pollen from different pollen seasons.     

Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary artery disease

Although first suggested at the turn of the 20th century, there is a renewed interest in the infectious theory of atherosclerosis. Studies done in many laboratories around the world over the past several years have shown an association between markers of inflammation and coronary atherosclerosis with an exacerbation of the inflammatory process during acute myocardial ischemia, particularly in the early stages of reperfusion. It is also being recognized that the traditional risk factors, such as smoking, dyslipidemia, hypertension and diabetes mellitus, do not explain the presence of coronary atherosclerosis in a large proportion of patients. We believe that in certain genetically susceptible people, infection with very common organisms, such as Chlamydia pneumoniae or cytomegalovirus, may lead to a localized infection and a chronic inflammatory reaction. Persistence of infection may relate to the degree of inflammation and severity of atherosclerosis. Early trials with appropriate antibiotic agents in some patients with a recent history of acute myocardial infarction have led to very salutary results. If patients with an infectious basis of atherosclerosis can be identified, a therapy directed at eradication of the offending organism may be appropriate.     

Prevalence of extracranial carotid and vertebral artery disease in Chinese patients with coronary artery disease

Electrotonic responses recorded extra- or intracellularly from peripheral nerve preparations show a "sag" to hyperpolarizing current pulses. The biophysical nature of this "inward rectification" is still under discussion since the phenomenon has not been noted at voltage-clamped single nerve fibres, and since Cs+, which reduces inward rectification, is not a specific ion channel blocker. In this study, we found that low micromolar concentrations of ZD 7288, a specific blocker of the hyperpolarization-activated cationic current (Ih) in the soma of central mammalian neurons, result in a complete block of inward rectification in the electrotonic responses of isolated rat spinal dorsal roots. In addition, ZD 7288 enhanced the activity-dependent slowing of conduction seen in compound C fibre action potentials of isolated rat vagus nerves and augmented the post-tetanic hyperpolarization following trains of action potentials in unmyelinated and myelinated axons. The data suggest that ZD 7288 is a potent blocker and a useful research tool for the study of hyperpolarization-activated inward rectification (Ih) of peripheral nerve preparations.     

Cardiovascular risk factors associated with clinically isolated and diffuse atherosclerosis in Spanish patients with coronary artery disease

BACKGROUND: Patients with coronary artery disease (CAD) associated with peripheral (PAD) or cerebrovascular disease (CVD), a condition called diffuse atherosclerosis, have a higher risk of death than patients with isolated CAD. The prevalence of diffuse atherosclerosis and the atherogenic risk factors associated with this condition in our geographic area have not been described previously. METHODS: A cohort of 2597 patients (62 +/- 10.8 years, 665 women) consecutively admitted at Bellvitge Hospital because of acute coronary syndromes were studied. CAD patients were divided in two groups with diffuse and located atherosclerosis according to whether they had or they had not an associated PAD or CVD. Baseline history, physical data and lipid profile were recorded in each patient according to a standardized questionnaire. RESULTS: A total of 370 patients (14.2%) had diffuse atherosclerosis. Among them, there were more men and women older than 55 years than among those with isolated CAD. Patients with diffuse atherosclerosis were more frequently hypertensive, diabetic and former smokers than those with isolated CAD (60.5% vs. 49.4%, P < 0.01; 37.4% vs. 24.5%, P < 0.01; and 47% vs. 35.7%, P < 0.01, respectively). There were no significant differences in the mean values of total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and triglycerides between both groups of patients, but patients with diffuse atherosclerosis had a lower HDL-C/TC ratio, with borderline statistical significance (0.18 +/- 0.06 vs. 0.19 +/- 0.06, P = 0.06). Using multiple logistic regression analysis, the variables associated with diffuse atherosclerosis in men were age greater than 55 years (OR 1.97, CI 1.33-2.93), hypertension (OR 1.50, CI 1.14-2.20), diabetes (OR 1.78, CI 1.20-2.70), smoking (former smokers) (OR 2.09, CI 1.36-3.24) and HDL-C/TC < 0.20 (OR 1.60, CI 1.18-2.17); and in women hypertension (OR 3.43, CI 1.48-7.94) and diabetes (OR 2.58, CI 1.55-4.80). CONCLUSIONS: Clinically overt diffuse atherosclerosis is a relatively common disease. Older patients and those with hypertension, diabetes or low HDL-C/TC ratio are more likely to have diffuse atherosclerosis than those without these conditions.     

Lipoprotein(a) interactions with lipid and nonlipid risk factors in early familial coronary artery disease

An interaction between high plasma lipoprotein(a) [Lp(a)], unfavorable plasma lipids, and other risk factors may lead to very high risk for premature CAD. Plasma Lp(a), lipids, and other coronary risk factors were examined in 170 cases with early familial CAD and 165 control subjects to test this hypothesis. In univariate analysis, relative odds for CAD were 2.95 (P < .001) for plasma Lp(a) above 40 mg/dL. Nearly all the risk associated with elevated Lp(a) was found to be restricted to persons with historically elevated plasma total cholesterol (6.72 mmol/L [260 mg/dL] or higher) or with a total/HDL cholesterol ratio > 5.8. Nonlipid risk factors were also found to at least multiply the risk associated with Lp(a). When Lp(a) was over 40 mg/dL and plasma total/HDL cholesterol > 5.8, relative odds for CAD were 25 (P = .0001) in multiple logistic regression. If two or more nonlipid risk factors were also present (including hypertension, diabetes, cigarette smoking, high total homocysteine, or low serum bilirubin), relative odds were 122 (P < 1 x 10(-12)). The ability of nonlipid risk factors to increase risk associated with Lp(a) was dependent on at least a mildly elevated total/HDL cholesterol ratio. In conclusion, high Lp(a) was found to greatly increase risk only if the total/HDL cholesterol ratio was at least mildly elevated, an effect exaggerated by other risk factors. Aggressive lipid lowering in those with elevated Lp(a) therefore appears indicated.     

Perioperative assessment and management of risk from coronary artery disease

PURPOSE: To summarize available evidence on preoperative cardiac risk stratification so that the internist may 1) use clinical and electrocardiographic findings to stratify a patient's perioperative risk for myocardial infarction and death; 2) decide which tests provide useful additional risk-related information; and 3) understand the benefits, risks, and evidence surrounding the decision to undertake coronary revascularization before elective noncardiac surgery. DATA SOURCES: A MEDLINE search and review of the reference lists of identified articles. Sensitivities, specificities, and likelihood ratios for diagnostic tests were calculated, and a quality rating for study methods was applied. DATA EXTRACTION: Myocardial infarction and mortality were the major outcomes considered, and a quality rating for study methods was applied. DATA SYNTHESIS: Clinical and electrocardiographic findings, organized by multivariate prediction indices, accurately identify patients as having low, intermediate, or high risk for myocardial infarction or death. Pharmacologic stress imaging with thallium or echocardiography probably improves risk stratification for intermediate-risk patients having vascular surgery. These tests have not been shown to be effective prognostic indicators for patients having nonvascular surgery. No studies of angiography for risk prediction have been reported. Decision analyses and retrospective series suggest that the risks incurred by doing coronary angiography and revascularization before elective surgery outweigh the benefits. Prospective, controlled studies of coronary revascularization are lacking. Evidence from a randomized, controlled trial has shown a survival benefit with the perioperative use of beta-blockers in patients at risk for coronary artery disease. CONCLUSIONS: Evaluation of all surgical patients by use of clinical indices is recommended. Low-risk patients need no further evaluation before surgery. High-risk patients need optimal management of their high-risk problems, including (if appropriate) beta-blocker use, and may need to have their elective procedures canceled. Intermediate-risk patients probably benefit from further noninvasive stress testing, especially if they are having vascular surgery. Further clinical trials are needed for most areas of concern.     

A quantitative analysis of the relationship between the Cook-Medley Hostility Scale and traditional coronary artery disease risk factors.

One possible explanation for the association between Cook-Medley Hostility Scale (Ho Scale; W. W. Cook & D. M. Medley, 1954) scores and premature coronary artery disease (CAD) morbidity and mortality is that hostile persons also have elevations on CAD risk factors. Meta-analyses with fixed and random-effects models were used to evaluate the relationship between Ho Scale scores and CAD risk factors in the empirical literature. Ho Scale scores were significantly related to body mass index, waist-to-hip ratio, insulin resistance, lipid ratio, triglycerides, glucose, socioeconomic status (SES), alcohol consumption, and smoking. Although there was also heterogeneity among study outcomes, the results of conservative random effects models provide confidence in the obtained relationships. On the basis of available evidence, researchers might give attention to obesity, insulin resistance, damaging health behaviors, and SES as potential contributing factors in understanding the association between Ho Scale scores and CAD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Management of risk factors after coronary heart disease in European countries

BACKGROUND: Despite clinical and epidemiological evidence of benefits from sustained management of vascular risk factors following coronary heart disease, the implication of physicians in secondary prevention remains limited. In 1994, several European scientific societies published jointly guidelines for the prevention of coronary heart disease in clinical practice, ranking as the highest priority the reduction of risk factors in coronary patients. METHODS: The European Society of Cardiology launched at the same period a study on the prevalence and management of vascular risk factors of coronary patients in Europe, the EUROASPIRE project. Six months after a coronary event 3,569 patients, from a total population of 4,863 affected individuals recruited in hospitals of 9 European countries, were interviewed and examined to estimate the levels and management of their vascular risk factors. RESULTS: At least six months after discharge, one patient out of five kept on smoking, one out of four was still obese, one out of two had high blood pressure levels and 44% total cholesterolemia over 5.5 mmol/L. More than 8 smoking patients out of 10 attempted to stop smoking and 8 obese patients out of 10 attempted to lose weight. More than 40% of patients, treated or not for hypertension, had systolic blood pressure levels over 140 mm Hg, and almost one patient out of two, treated or not treated for dyslipemia, a total cholesterolemia over 5.5 mmol/L. CONCLUSIONS: Given the high prevalence of vascular risk factors in coronary patients, efficient secondary prevention aiming at the reduction of the levels of these risk factors, may have a major impact on the decrease of morbidity and mortality of these patients. Thus, joined European efforts to elaborate, diffuse and evaluate secondary prevention strategies towards physicians and patients should be rapidly developed to facilitate the achievement of such benefits for coronary patient health.     

Association of risk factor variables and coronary artery disease documented with angiography

Stepwise linear discrimination was used to analyze risk factors in 431 consecutive patients who underwent coronary angiography to determine which variables were most closely associated with coronary artery disease. Twenty-one risk factors were considered: total plasma cholesterol and triglycerides; the cholesterol and triglyceride content of high-density lipoproteins (HDL), low-density lipoproteins (LDL) and very low density lipoproteins (VLDL); and the percentage of total cholesterol and triglycerides in each fraction. Age, smoking history, family history, hypertension, diabetes mellitus and relative weight were also considered. Coronary artery disease was assessed using three standard grading scores. There were significant differences in risk factors between males and females. In males, LDL cholesterol and age were selected by multivariate analysis. In females, the ratio of HDL cholesterol to total cholesterol, as well as relative weight, family history, age and smoking were selected. The discriminating value of HDL cholesterol as the percentage of total cholesterol was significantly greater than that of HDL cholesterol itself. Despite highly significant associations between risk factors and the presence of coronary artery disease, the discrimination did not provide sufficient separation of the groups to give results that are useful diagnostically in individual patients.     

Lipid-lowering therapy for patients with or at risk of coronary artery disease

Several studies have shown that effective lipid-lowering therapy slows the progression of atherosclerotic lesions in the coronary and carotid arteries. Recent clinical trials have confirmed and extended previous work showing that lowering cholesterol reduces the risk of coronary events. A clear reduction in major coronary events during treatment for 5 years with the hydroxymethylglutaryl-coenzyme A reductase inhibitor pravastatin was observed in the West of Scotland study and in the preliminary results of the Cholesterol and Recurrent Events study. The Scandinavian Simvastatin Survival Study has provided the first unequivocal demonstration of improved survival as a result of lipid-lowering therapy. These three trials, which together included over 15,000 patients studied for 5 years, have provided good evidence that noncardiovascular mortality is not affected by substantial reductions in blood cholesterol.     

Relationship between obesity and risk factors of coronary heart disease in nondiabetics

We analysed the data of 395 nondiabetic obese (BMI 25-42.2, impaired glucose tolerance, IGT, 257 and normal glucose tolerance, NGT, 138) and 482 nonobese subjects (BMI 15.9-24.9, IGT 170 and NGT 312). The blood pressure, plasma glucose, insulin, triglyceride and total cholesterol in obese were higher than that in nonobese, while HDL-c level was lower after controlling for age and sex (P < 0.001). This difference remained to be significant even after the adjustment of age, sex, insulin and 2-hours plasma glucose. Therefore, it was suggested that obesity was easy of access to coronary heart disease risk factors independent of hyperglycemia and hyperinsulinemia.     

Prevalence of coronary heart disease and major cardiovascular risk factors in Thailand

BACKGROUND: Coronary heart disease (CHD) is expected to become one of the major health problems in developing countries such as Thailand where prevalence data are scarce. This study reports the prevalence of CHD, as indicated by electrocardiogram (ECG) Minnesota coding, and its risk factors in Thailand. METHODS: In 1991 we conducted a cross-sectional ECG survey in a multistage random sample of the Thai population, aged > or =30. All major cardiovascular risk factors were measured. Standard supine 12-lead ECG data were collected; amplitudes and intervals were measured manually and entered into a computer. Abnormal tracings were verified by five cardiologists, and agreement among at least three of them was accepted as final. RESULTS: The total sample included 3822 men and 4967 women aged > or =30 years. The age-standardized prevalence rate of CHD was 9.9/1000 (men 9.2/1000, women 10.7/ 1000). The age-standardized level of major cardiovascular risk factors among men and women respectively were: total cholesterol 4.8 mmol/l (187.3 mg/dl), 5.1 mmol/l (197.7 mg/dl); hypercholesterolaemia (> or =6.2 mmol/l) 12.2%, 16.9%; systolic blood pressure (mmHg) 117.8, 117.7; diastolic blood pressure (mmHg) 76.9, 75.8; body mass index (kg/m2) 21.7, 22.8; fasting blood sugar 4.8 mmol/l (87.9 mg/dl), 5.0 mmol/l (90.3 mg/dl); hypertension (> or =160/95 +/- on antihypertensive drugs) 6.3%, 8.1%; smoking 65.1%, 8.5%; diabetes mellitus (> or =7.8 mmol/l) 2.4%, 3.7%; obesity (>25 kg/m2) 15.2%, 27.2%. CONCLUSIONS: Most of the age-adjusted mean values and proportion of major cardiovascular disease risk factors as well as the prevalence of total CHD in the Thai population were much lower than the median of those values found in developing countries.     

Effects of antihypertensive drugs on coronary artery disease risk: a meta-analysis

1. The effects of antihypertensive drugs on lipids may also influence their effect on coronary artery disease (CAD). However, the clinical significance of these effects and the extent to which they persist during long-term therapy is uncertain. 2. We performed a meta-analysis on 23 randomized trials published between 1988 and 1994 that compared the effects of atenolol, celiprolol (a beta-blocker with beta 2-adrenoceptor intrinsic sympathomimetic activity), enalapril, nifedipine and doxazosin on plasma cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides and blood pressure (BP). 3. Predicted changes in CAD risk were calculated by incorporating the results for these parameters into the Framingham equations. 4. While there were no differences in antihypertensive efficacy between the drugs, atenolol significantly (P < 0.05) reduced HDL-C and increased total cholesterol, LDL-C and triglycerides compared with celiprolol, enalapril, doxazosin and nifedipine. 5. The magnitude of the effects on lipids was not significantly influenced by the duration of therapy (up to 3 years for atenolol and doxazosin and up to 2 years for celiprolol). 6. The improvement in Framingham equation point scores (systolic BP formula) was significantly (P < 0.05) less for atenolol (-0.54; confidence intervals (CI) -0.29-(-0.78)) than for celiprolol (-1.69; CI -0.68-2.70), doxazosin (-1.67; CI -1.11-(-2.23)), enalapril (-1.43; CI 0.23-(-3.07)) and nifedipine (-1.91; CI -1.22-(-2.59)). Similar results were obtained for the Framingham diastolic BP formula. 7. These results suggest that the adverse effects of atenolol ]on plasma lipids do not improve with prolonged therapy and are theoretically great enough to reduce its efficacy in reducing CAD by approximately two thirds compared with antihypertensive drugs that do not adversely affect plasma lipids. However it must be emphasized that these are theoretical effects. In order to determine the actual differences between these drugs on CAD end points, studies using these end points are required.