CoronaryArteryDiseaseRiskFactors

Coronary Artery Disease -Risk Factors
     

• Ridker PM, Hennekens CH, Roitman-Johnson B, et al [ Brigham and Women’s Hosp, Boston; Harvard Med School, Cambridge, Mass; Harvard School of Public Health, Boston; et al]
  Plasma Concentration of Soluble Intercellular Adhesion Molecule 1 and Risks of Future Myocardial Infarction in Apparently Healthy Men
  Lancet 351: 88-92, 1998
       
  Leukocyte adhesion and transmigration to the vascular endothelial wall is thought to be a key step in the atherosclerotic process. This step is mediated by intercellular adhesion molecule [ICAM-1].
     
  It is unknown whether otherwise healthy people who go on to have acute myocardial infarction have elevated concentrations of soluble ICAM-1 [s/CAM-1]. This question was addressed using data from the Physicians’ Health Study.
      
  The study was based on prospectively collected baseline plasma samples from nearly 15,000 healthy U.S. male physicians. Concentrations of s/CAM-1 were measured in the samples of 474 research subjects with their first myocardial infarction and 474 controls who remained healthy during a 9-year follow-up period. The cases and controls were matched in terms of age and smoking status at the time of myocardial infarction. The effects of baseline s/CAM-1 concentration on myocardial infarction risk were analyzed, including the influence of other lipid and nonlipid cardiovascular risk factors. A high sICAM-1 concentration was associated with an increased risk of myocardial infarction. For men in the highest quartile of S/CAM-1 concentration- greater than 260 hg/ml- the relative risk was 1.6, with a 95% confidence interval of 1.1 to 2.4. This relationship was present even in nonsmokers and after adjustment for other risk factors. Multivariate analysis suggested a 1.8 relative risk [ 95% confidence interval, 1.1 to 2.8] for subjects in the highest quartile of s/CAM-1 concentration. Although s/CAM-1 level was significantly correlated with fibrinogen, high-density lipoprotein cholesterol, homocysteine, triglycerides, tissue-type plasminogen-activator antigen, and C-reactive protein, adjusting for these risk factors had little impact on risk. The effects of s/CAM-1 level on myocardial infarction risk appeared to increase with longer follow-up.Thus elevated baseline concentration of s/CAM-1 is associated with an increased risk of later acute myocardial infarction. The findings strengthen the suggestion that ICAM-1 and other cellular mediators of inflammation are involved in the atherogenic process. They also suggest that anti-adhesion treatments could offer a new approach to the prevention of cardiovascular disease. 
    
• Danesh J, Collins R, Appleby P, et al [ Univ of Oxford, England]
  Association of Fibrinogen, C-Reactive Protein, Albumin, or Leucocyte Count with Coronary Heart Disease: Meta -Analyses of Prospective Studies 
  Jama 279: 1477-1482, 1998
    
  Association between coronary heart disease and blood levels of fibrinogen, C-reactive protein, albumin and leukocyte count have been reported. The short term can be influenced by insults that trigger acute phase reactions. A meta- analyses of the available evidence from published prospective epidemiologic studies was conducted to determine the nature of the associations between coronary heart disease and these factors. MEDLINE searches were conducted to find long-term prospective studies published before 1998 that reported on correlations between coronary heart disease and fibrinogen, C-reactive protein, albumin and leukocyte count. Other sources of information were from scanning of relevant reference lists, hand searching of cardiology, epidemiology, and other relevant journals, and discussions with authors of relevant reports. 
    
  There were 4018 patients with coronary heart disease in 18 studies in which fibrinogen was studied. Patients in the top third were compared with those in the bottom third of the baseline measurements. A combined risk ratio of 1.8 was associated with a difference in long-term usual mean fibrinogen levels of 0.1g/dL between the top and bottom thirds [0.35 vs. 0.25 g/dL].
     
  There were 1053 patients with coronary heart disease in 7 studies in which C-reactive protein was studied. The result was a combined risk ratio of 1.7 that was associated with a difference of 4 g/L [38 vs. 42 g/L for an inverse association].
    
  There were 5337 patients with coronary heart disease in the 7 largest studies in which leukocyte count was studied. The result was an associated risk ratio of 1.4 associated with a difference of 2.8 x 109 /L [8.4 vs. 5.6 x 109/L].
      
  There are moderate but highly statistically significant associations with coronary heart disease; relevance of these associated factors to the causation of coronary heart disease needs to be further studied, though the mechanisms that might account for such associations remain unclear.
     
• Birkmeyer NJO, for the Northern New England Cardiovascular Disease Study Group [ Dartmouth Med School, Hanover, NH; Optima Health Care, Manchester, NH, Eastern Maine Med Ctr, Bangor, et al]
  Obesity and Risk of Adverse Outcomes Associated with Coronary Artery Bypass Surgery
  Circulation 97: 1689-1694, 1998
       
  Obesity is thought to be a high risk factor for perioperative morbidity and mortality, with cardiac and other major surgery. These perceptions are contributed by factors associated with obesity, such as hypertension, hypercholesterolemia, and diabetes. The independent combination of obesity to risks of in-hospital death, intra-and post-operative cerebrovascular accident, postoperative bleeding, and sternal wound infection, associated with coronary artery bypass grafting was assessed.
     
  There were 11,101 patients having coronary artery bypass grafting, for which data was collected on age, sex, height, weight, medical history, current medical status, and treatment factors. Body mass index was used as the measure of obesity. Nonobese was categorized as first to 74th percentiles, obese was categorized as 75th to 94th percentiles, and severely obese was categorized as 75th to 94th percentiles, and severely obese was categorized as 95th to 100th percentiles. Factors that were defined prospectively included adverse outcomes occurring in hospital, death intraoperative/postoperative cerebrovascular accident, postoperative bleeding and sternal infection. Logistic regression was used to assess association between obesity and postoperative outcomes to adjust for potentially confounding variables. 
      
  Increased mortality rate or postoperative cerebrovascular accidents were not associated with obesity, but risks of sternal infection were substantially increased in obese and severely obese; also rates of postoperative bleeding were significantly lower in the obese and severely obese.
   
  The perception among clinicians that obesity predisposes to various postoperative complications with coronary artery bypass grafting is not supported, with the exception of sternal infection.
      
• Avorn J, Monette J, Lacour A, et al [Harvard Med School, Boston; Universite de Montreal]
  Persistence of Use of Lipid-Lowering Medications : A Cross National Study
  Jama 279: 1458-1462, 1998
    
  The clinical usefulness of lipid-lowering regimens has been documented in reducing rates of cardiac morbidity and mortality. Little is known about how these drugs are taken outside managed care settings, among the poor, among minorities, and in those older than 65 years. Reasons for stopping use of a drug include patient noncompliance or a physician decision to discontinue therapy when adverse effects outweigh benefits. Predictors of persistence with therapy were estimated in typical populations of patients in Canada and United States.
     
  There were 5611 Medicaid patients in USA and 1676 patients older than 65 years in Canada, who were studied for 1 year. The proportion of days during the year the patient had lipid-lowering drugs, was followed as well as predictors of good vs poor persistence with therapy. The drugs taken included clofibrate, colestipol, cholestyramine, gemfibrozil, niacin, probucol, and 3-hydroxy-3-methylglutaryl coenzyme.
      
  For about 40% of the study year, patients did not fill prescriptions for lipid-lowering drugs in both populations. There were higher persistence rates with 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitors. Significantly higher rates of persistence were seen in patients with hypertension, diabetes, or coronary artery disease. Lower rates of drug use were seen among poorest patients compared with less indigent, despite virtually complete drug coverage. Only 52% of surviving patients were still filling prescriptions for drugs when rates of use were measured in the US population for 5 years after the study.
    
  For more than a third of the year under study, patients did not fill prescriptions for lipid lowering drugs. In the choice of drug prescribed, comorbidity, socioeconomic status, rates of persistence varied despite universal coverage of drugs costs. Lipid-lowering therapy was stopped altogether by about half the surviving original cohort in the US after 5 years.
       
• Jeppesen J, Hein HO, Saudicani P, et al [ Copenhagen Univ Hosp; Glostrup Univ Hosp, Denmark]
  Triglyceride Concentration and Ischemic Heart Disease: An Eight-Year Follow-up in the Copenhagen Male Study
  Circulation 97: 1029-1036, 1998
      
  There is continuing debate about the significance of triglycerides [TG] as a risk factor for ischemic heart disease [IHD]. Most studies have found a positive relationship between TG levels and IHD risk; however, after adjustment for high density lipoprotein cholesterol [HDL-C], the predictive value of TG is eliminated or diminished. Data from a large prospective study were evaluated to assess the relationship between fasting TG level and IHD risk.
      
  The analysis included data on 2906 men, aged 53 to 74 years. All patients were free of overt cardiovascular disease at baseline, when measurements of fasting lipids and other IHD risk factors were obtained. Eight year follow up data were analyzed to examine the effect of TG levels on risk of IHD, compared with HDL-C levels. 
     
  An initial IHD episode occurred in 229 men during the follow-up. The rate of such events was 4.6% for men in the lowest third of TG level, 7.7% for those in the middle third, and 11.5% for those in the highest third. After adjustment for other risk factors, such as age, body mass index, alcohol, smoking, physical activity, hypertension, non-insulin dependent diabetes mellitus, social class, low density lipoprotein-cholesterol and HDL-C, patients with higher TG levels were at higher risk for IHD. Relative risks were 1.5 [95% confidence interval, 1.0 to 2.3] for men in the middle third of TG levels and 2.2 [95% confidence interval, 1.4 to 3.4] for men in the highest third. After stratification by HDL-C level, IHD risk clearly increased within each level of HDL-C. This was so even among men with a high HDL-C level, which is believed to be protective against IHD. Thus high TG levels are an important risk factor in men, independent of high HDL-C levels and measurements of TG levels must be included in the risk factor profiles, with increased attention of levels above 2.5 mmol/L.
       
• Hulley S, for the Heart and Estrogen/Progestin Replacement Study [HERS] Research Group [Univ of California, San Fransisco, Johns Hopkins Univ, Baltimore, Md; Wake Forest Univ, Winston-Salem, NC; et al]
  Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women
  JAMA 280: 605-613, 1998
    
  Observational studies report that coronary heart disease [CHD] rates are lower in postmenopausal women who take estrogen than in those who do not. However, this potential has not been confirmed in clinical trials. The effect of estrogen plus progestin therapy on risk of CHD events in postmenopausal women with established coronary disease was investigated in a randomized, blinded, placebo-controlled, secondary prevention trial.
    
  A total of 2763 women with CHD seen in outpatient and community settings at 20 U.S. clinical centres were included. All were younger than 80 years, with a mean age of 66.7 years. All were postmenopausal and had an intact uterus. The women were given either daily doses of 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate or placebo. The mean follow-up was 4.1 years. Eighty-two percent of the women assigned to hormone treatment were still using the therapy at the end of 1 year, and 75% at the end of 3 years.
     
  The occurrence of nonfatal myocardial infarction or death from CHD was comparable in two groups, despite a net 11% lower low-density lipoprotein cholesterol level and 10% higher high-density lipoprotein cholesterol level in he hormone group. There was a significant time trend, with more CHD events occurring in the hormone group than the placebo group within the first year and fewer in years 4 and 5. A greater proportion of the women in the hormone group had venous thromboembolic events and gallbladder disease. Several other end points, for which the statistical power was limited, were also comparable between groups, including fractures, cancer and total mortality. Hormone treatment did not decrease the overall rate of CHD events in postmenopausal women with established coronary disease. However, it did increase the rate of thromboembolic events and gallbladder disease. Based on findings of no overall cardiovascular benefit and a pattern of early increase in the risk of CHD events, this treatment is not recommended for the secondary prevention of CHD. However, continuing this treatment in women already receiving it may be appropriate.