Chlamydia pneumoniae and future risk in patients with coronary heart disease

AIM: To evaluate the association between previous exposure to Chlamydia pneumoniae and future coronary risk in patients with coronary heart disease. METHODS: A prospective, nested, case-control design was used. The patient sample was derived from a trial study of bezafibrate for the treatment of coronary heart disease. Anti-Chlamydia pneumoniae antibodies (IgG and IgA) in the baseline sera of 136 patients who had coronary events during follow-up (mean 6.2 years) were compared with those in 136 age- and gender-matched patients from the same trial without subsequent coronary events. RESULTS: Mean titers of IgG and IgA antibodies were similar in cases and controls. The relative odds of future coronary events in patients who were seropositive at baseline were 1.0 (95% CI, 0.54-1.84) for IgG and 0.74 (95% CI, 0.41-1.31) for IgA. The relative odds did not change after adjustment for multiple confounding variables. The risk of future coronary events did not increase with increasing anti-Chlamydia pneumoniae antibody titers. CONCLUSIONS: Prior exposure to Chlamydia pneumoniae in patients with chronic coronary heart disease is not associated with increased risk of recurrent coronary events.     

可溶性粘附分子与冠状动脉支架植入后心脏事件的关系

目的:检测冠心病患者冠状动脉支架植入前的可溶性细胞粘附分子水平,探讨其与以后以发生心脏事件的关系。方法:对2000年4月～2002年3月在我院接受冠状动脉支架植入的107例患者,以ELISA法检测支架植入前基础血浆可溶性粘附分子水平,并进行随访。结果:20例患者失访,随访率81.3％,随访时间3～24(平均17.4)月。随访期间心绞痛症状复发13例(14.9％),非致命性心梗2例(2.3％),猝死1(1.1％)。发生心脏事件组基础可溶性细胞间粘附分子-1(sICAM-1)水平较无心脏事件组升高(P<0.01),而可溶性血管细胞粘附分子-1(sVCAM-1)、可溶性E选择素(sE-selectin)水平在两组间无显著性差异(P>0.05)。以Kaplan-Meier法计算无心脏事件生存率,slCAM-1≥276ng/ml组2年无心脏事件生存率为67.8％,而sICAM-1<276ng/ml组为88.4％,两组间有显著性差异(P<0.01)。结论:冠状动脉支架植入前基础血浆sICAM-1水平升高的患者术后无心脏事件生存率低,sICAM-1可作为冠状动脉支架植入后心脏事件发生的预测指标。     

Reflection in the arterial system and the risk of coronary heart disease

BACKGROUND: Although it was reported that the augmentation index and inflection time are closely related to reflection in the arterial system and large artery function, it is not known whether these indices of the ascending aortic pressure waveform increase the risk of coronary heart disease (CHD). The purpose of this study was to evaluate whether the aortic reflection of the ascending aortic pressure waveform is related to an increased risk of CHD. METHODS: We enrolled 190 men and women who had chest pain, normal contractions, no local asynergy, and no history of myocardial infarction. We measured the ascending aortic pressure using a fluid-filled system. The inflection time was defined as the time interval from initiation of a systolic pressure waveform to the inflection point. We investigated the association between the inflection time and augmentation index of the ascending aorta and the risk of CHD. RESULTS: Both the inflection time and augmentation index were associated with an increased risk of CHD. The crude prevalence rates of CHD were 66.0% for the shortest quartile and 10.6% for the longest quartile of the inflection time, and 17.0% for the lowest quartile and 40.4% for the highest quartile of the augmentation index. The multiple-adjusted odds ratio of CHD was 30.8 (95% confidence interval [CI] 7.43-128.05) for the shortest quartile of the inflection time compared with the longest quartile and was 3.82 (95% CI 1.26-11.59) for the highest quartile of the augmentation index compared with the lowest quartile. CONCLUSIONS: The augmentation index and inflection time were associated with an increased risk of CHD.     

Ankle brachial pressure index usefulness as predictor factor for coronary heart disease in diabetic patients

Ankle brachial pressure index (ABPI) is a non-invasive marker of atherosclerosis, helpful to identify subjects at high-risk for coronary heart disease (CHD) among large populations with cardiovascular disease (CVD) risk factors. The diagnostic role of ABPI has been also recognized in patients with diabetes. In the present study, the role of an ABPI score < 0.90 in predicting CHD has been evaluated in a large series of patients with Type 2 diabetes mellitus and compared to other known CVD risk factors. Nine hundred and sixty-nine (mean age was 66.1 yr) consecutive patients with Type 2 diabetes mellitus were evaluated. The patients were followed-up for 18.3+/-5.2 months (range 12- 24) and all events of CHD, defined as myocardial infarction, unstable and resting angina or coronary atherosclerosis at the instrumental investigation (at the coronary angiography and/or perfusion stress testing) were recorded. A rate of 17.5% of CHD events were recorded in diabetic population during the follow-up period. The relative risk of CHD was significantly increased for male patients [odds ratio (OR): 1.6; 95% confidence interval (CI): 1.1-2.2], patients with age > or = 66 yr (OR: 1.8; 95% CI: 1.3-2.5), body mass index (BMI) > 30 (OR: 1.5; 95% CI: 1.1-2.1), waist circumference > 88 cm for females and 102 cm for males (OR: 1.5; 95% CI: 1.0-2.1), proteinuria > or = 30 microg per min (OR: 1.6; 95% CI: 1.1-2.3), LDL-cholesterol > or = 100 mg/dl (OR: 2.1; 95% CI: 1.5-3.0), glycated hemoglobin > 7% (OR: 1.6; 95% CI: 1.1-2.3), insulin therapy (OR: 1.9; 95% CI: 1.3-2.9), and ABPI < 0.90 (OR: 3.7; 95% CI: 2.2- 6.2). BMI was higher in patients with ABPI < 0.90 than in those with ABPI > or = 0.90 (p<0.05). At the multivariate analysis, ABPI < 0.90 was the best factor independently associated with CHD (p<0.001). APBI < 0.90 is strongly associated to CHD in Type 2 diabetic patients. We recommend to use ABPI in diabetic patients and to carefully monitor diabetic subjects with an ABPI lower than 0.90.     

Association of renal functional impairment and the severity of coronary artery disease.

OBJECTIVE: Cardiovascular diseases are the most common cause of death in patients with renal failure. Glomerular filtration rate (GFR) is used for the assessment of the renal functional status. In this study we aimed to examine the association between severity of coronary stenosis and renal function by quantifying the coronary lesions, angiographically and calculating the renal function with the use of GFR. METHODS: Forty-three patients with decreased renal function (calculated GFR<80 ml/min) with a mean age of 67.8+/-9.0 years and 49 patients without impaired renal function (calculated GFR>/=80 ml/min) with a mean age of 52.5+/-10.3 years were studied consecutively from March 2005 to September 2005. Glomerular filtration rate was calculated according to a given formula. All patients underwent selective coronary artery angiography and Gensini scoring system was used for the detection of severity of coronary atherosclerosis. RESULTS: In linear regression analysis, a negative correlation was found between renal function and the severity of coronary atherosclerosis (r=0.326, p=0.002). All patients were classified into quartiles of Gensini score level. In multivariate analysis, the multiple-adjusted odds ratio (OR) of the risk of decreased renal function was 0.99 (95% CI 0.24-4.15) for quartile 2, 4.38 (95% CI 1.11-17.20, p=0.03) for quartile 3, and 7.01 (95% CI 1.72-28.61, p=0.007) for quartile 4 of Gensini score level compared with the quartile 1. CONCLUSION: Coronary atherosclerosis quantified by Gensini score is significantly associated with the severity of decreased renal function and this association is independent of age and other cardiovascular risk factors.     

Serum levels of soluble adhesion molecules as prognostic factors for acute liver failure

Background/Aims: In patients with septic shock, the degree of liver dysfunction is correlated with serum levels of soluble intercellular adhesion molecule (sICAM)-1. We aimed to assess the usefulness of serum levels of soluble adhesion molecules as prognostic factors for acute liver failure (ALF). Methods: Serum levels of soluble platelet endothelial cell adhesion molecule (sPECAM)-1, sICAM-3, soluble endothelial (sE) selectin, sICAM-1, soluble platelet selectin, and soluble vascular cell adhesion molecule-1 on admission were measured in 37 ALF patients and 34 healthy controls. Results: Twenty-two ALF patients (59%) reached to fatal outcomes. Serum levels of sPECAM-1, sICAM-3, sE-selectin and sICAM-1 were higher in ALF patients than healthy controls. In 37 ALF patients, by the multivariate logistic regression analysis, ratio of direct to total bilirubin (per 0.1 increase; OR 0.11, 95% CI 0.01-0.99), serum sPECAM-1 level (per 100 ng/ml increase; OR 4.37, 95% CI 1.23-15.5) and serum sICAM-1 level (per 100 ng/ml increase; OR 0.49, 95% CI 0.27-0.89) were associated with fatal outcomes. Using receiver operating characteristics curve, each area under the curve of serum sPECAM-1 and sICMA-1 levels as prognostic factors was 0.71 and 0.74, respectively. Conclusion: Serum sPECAM-1 and sICAM-1 levels may be useful for predicting the prognosis of ALF.     

Risk of coronary heart disease in subjects with chest discomfort: the Framingham Heart Study

PURPOSE: To examine the risk of coronary heart disease (CHD) events in subjects of the Framingham Study reporting new chest discomfort. SUBJECTS AND METHODS: Original cohort subjects with chest discomfort were classified by their history into three groups: definite angina, possible angina, or nonanginal chest discomfort. Subjects were followed for 2 years for CHD events, including coronary insufficiency, myocardial infarction, or CHD death. RESULTS: Compared to that in subjects without chest discomfort, the relative odds of a CHD event was 3.7 (95% confidence interval [CI] 2.11, 6.60) in men with definite angina and 3.0 (95% CI 1.33, 6.69) in men with possible angina. Comparable increased CHD risk was also observed in women with definite or possible angina, with relative odds of 5.4 (95% CI 3.08, 9.30) and 2.9 (95% CI 1.13, 7.17), respectively. The increase in CHD risk associated with definite or possible angina persisted after adjustment for cardiac risk factor profile. There was no increase in risk associated with nonanginal chest discomfort. CONCLUSION: CHD risk is increased in subjects with new chest discomfort that on the basis of history is consistent with definite or possible angina, whereas CHD risk is not increased in subjects with nonanginal chest discomfort. The presence of chest discomfort and its characteristics facilitate the classification of subjects into meaningful categories that offer prognostic information beyond that provided by traditional CHD risk factors.     

Relation between soluble intercellular adhesion molecule-1, statin therapy, and long-term risk of clinical cardiovascular events in patients with previous acute coronary syndrome (from PROVE IT-TIMI 22)

High levels of adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1), are associated with long-term risk of cardiac events in patients with and without stable coronary artery disease. The relation between sICAM-1 and long-term risk after acute coronary syndromes (ACSs) and the influence of statin treatment has not been explored. Using a nested case-control design, patients with ACS who were enrolled in the PROVE IT-TIMI 22 trial were matched for age, gender, smoking, diabetes, type of ACS presentation, and revascularization for index event (583 patients with recurrent events vs 581 controls). Patients with recurrent events were identified as such by death, myocardial infarction, or hospitalization for recurrent ACS. Soluble ICAM-1 was measured at study entry (approximately 7 days after ACS). After adjusting for statin regimen and other risk factors, patients in quartiles 2 to 4 were at a higher risk of clinical events compared with those in quartile 1 (odds ratio 1.6 for quartile 4 vs 1, 95% confidence interval 1.1 to 2.3, p = 0.02). The risk of adverse events in patients with sICAM-1 levels in quartiles 2 to 4 was most marked in subjects who were allocated to standard dose statin therapy, even after adjusting for low-density lipoprotein cholesterol and C-reactive protein at day 30. The risk in quartiles 2 to 4 was somewhat attenuated in the intensive therapy group. In conclusion, in this large study of patients with ACS, we provide evidence that increased endothelial activation after ACS is independently associated with increased long-term risk of death, myocardial infarction, or recurrent ACS.     

Serum parathyroid hormone levels predict coronary heart disease: the Troms? Study.

BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with hypertension, coronary atherosclerosis and other cardiovascular diseases. We aimed to evaluate serum parathyroid hormone (PTH) levels as an independent risk factor for coronary heart disease (CHD) in subjects with serum calcium within the reference range. DESIGN: Population-based cross-sectional study. METHODS: The Troms? Study was attended by 27159 subjects aged 25-79 years. Serum PTH was measured in 3570 subjects. They all completed a questionnaire on medical history, including questions on angina pectoris and myocardial infarction along with a food-frequency questionnaire. A total of 1459 men and 1753 women with serum calcium 2.20-2.60 mmol/l, serum creatinine<121 micromol/l and who did not use diuretics were included in the present study. Linear regression was used to reveal associations between PTH, age, body mass index, serum calcium, calcium intake, cholesterol, blood pressure, glycosylated haemoglobin (HbA1c) and smoking status. A logistic regression model was used to find the independent predictors of CHD. RESULTS: When stratified for age the rate of CHD was higher in the subjects with serum PTH > 6.8 pmol/l than in those with normal or low serum PTH levels [relative risk 1.67, 95% confidence interval (CI) 1.26-2.23 in men and 1.78, 95% CI 1.22-2.57 in women]. The highest PTH quartile (> 3.50 pmol/l in men and > 3.30 pmol/l in women) predicted CHD, with odds ratios of 1.70 (95% CI 1.08-2.70) for men and 1.73 (95% CI 1.04-2.88) for women, versus the lowest PTH quartile (< 1.90 pmol/l for men and <1.80 pmol/l for women). CONCLUSIONS: Serum PTH predicts CHD in subjects with calcium levels within the reference range. This may indicate a role for PTH in the development of CHD.     

Dietary fiber intake and reduced risk of coronary heart disease in US men and women: the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study

BACKGROUND: Prospective studies suggest that dietary fiber intake, especially water-soluble fiber, may be inversely associated with the risk of coronary heart disease (CHD). METHODS: We examined the relationship between total and soluble dietary fiber intake and the risk of CHD and cardiovascular disease (CVD) in 9776 adults who participated in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study and were free of CVD at baseline. A 24-hour dietary recall was conducted at the baseline examination, and nutrient intakes were calculated using Food Processor software. Incidence and mortality data for CHD and CVD were obtained from medical records and death certificates during follow-up. RESULTS: During an average of 19 years of follow-up, 1843 incident cases of CHD and 3762 incident cases of CVD were documented. Compared with the lowest quartile of dietary fiber intake (median, 5.9 g/d), participants in the highest quartile (median, 20.7 g/d) had an adjusted relative risk of 0.88 (95% confidence interval [CI], 0.74-1.04; P =.05 for trend) for CHD events and of 0.89 (95% CI, 0.80-0.99; P =.01 for trend) for CVD events. The relative risks for those in the highest (median, 5.9 g/d) compared with those in the lowest (median, 0.9 g/d) quartile of water-soluble dietary fiber intake were 0.85 (95% CI, 0.74-0.98; P =.004 for trend) for CHD events and 0.90 (95% CI, 0.82-0.99; P =.01 for trend) for CVD events. CONCLUSION: A higher intake of dietary fiber, particularly water-soluble fiber, reduces the risk of CHD.     

Plasma N-terminal pro-B-type natriuretic peptide for prediction of death or nonfatal myocardial infarction following percutaneous coronary intervention

B-type natriuretic peptide (BNP) and the N-terminus of pro-BNP (NT-pro-BNP) have prognostic value in patients with heart failure and patients with acute coronary syndromes. Little is known about the prognostic value of baseline NT-pro-BNP alone or in combination with C-reactive protein (CRP) for clinical outcome after percutaneous coronary intervention (PCI). Within a single center registry of contemporaneous PCI, we investigated the prognostic value of baseline plasma NT-pro-BNP and CRP concentrations for the prediction of death or nonfatal myocardial infarction (MI) during 12 to 14 months of follow-up. Among 1,172 consecutive patients, the occurrence of death or MI increased significantly with baseline NT-pro-BNP before PCI (first quartile 0 of 294, second quartile 6 of 291 [2.1%], third quartile 4 of 294 [1.4%], fourth quartile 22 of 293 [7.5%)]; p <0.0001). NT-pro-BNP in the top quartile significantly predicted death (odds ratio [OR] 13.37, 95% confidence interval [CI] 4.50 to 40.38, p <0.0001) and was associated with nonfatal MI (OR 2.53, 95% CI 0.77 to 8.34, p = 0.22) An abnormal CRP was significantly associated with death (OR 3.47, 95% CI 1.26 to 9.54, p = 0.019). Stepwise multivariate logistic regression analysis identified age >65 years and NT-pro-BNP as independent significant predictors of death/MI (age OR 3.18, 95% CI 1.32 to 7.67, p = 0.01; NT-pro-BNP OR 4.57, 95% CI 2.07 to 10.10, p = 0.0001). Baseline NT-pro-BNP before PCI provides important, independent prognostic information for the occurrence of death or nonfatal MI during long-term follow-up.     

Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study

OBJECTIVE: To examine the risk of clinical coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) compared with age- and sex-matched non-RA subjects, and to determine whether RA is a risk factor for CHD after accounting for traditional CHD risk factors. METHODS: We assembled a population-based incidence cohort of 603 Rochester, Minnesota residents ages >or=18 years who first fulfilled the American College of Rheumatology (ACR) 1987 criteria for RA between January 1, 1955 and January 1, 1995, and 603 age- and sex-matched non-RA subjects. All subjects were followed up through their complete inpatient and outpatient medical records, beginning at age 18 years until death, migration, or January 1, 2001. Data were collected on CHD events and traditional CHD risk factors (diabetes mellitus, hypertension, dyslipidemia, body mass index, smoking) using established diagnostic criteria. CHD events included hospitalized myocardial infarction (MI), unrecognized MI, coronary revascularization procedures, angina pectoris, and sudden CHD deaths. Conditional logistic regression and Cox regression models were used to estimate the risk of CHD associated with RA, both prior to and following RA diagnosis, after adjusting for CHD risk factors. RESULTS: During the 2-year period immediately prior to fulfillment of the ACR criteria, RA patients were significantly more likely to have been hospitalized for acute MI (odds ratio [OR] 3.17, 95% confidence interval [95% CI] 1.16-8.68) or to have experienced unrecognized MIs (OR 5.86, 95% CI 1.29-26.64), and less likely to have a history of angina pectoris (OR 0.58, 95% CI 0.34-0.99) compared with non-RA subjects. After the RA incidence date, RA patients were twice as likely to experience unrecognized MIs (hazard ratio [HR] 2.13, 95% CI 1.13-4.03) and sudden deaths (HR 1.94, 95% CI 1.06-3.55) and less likely to undergo coronary artery bypass grafting (HR 0.36, 95% CI 0.16-0.80) compared with non-RA subjects. Adjustment for the CHD risk factors did not substantially change the risk estimates. CONCLUSION: Patients with RA have a significantly higher risk of CHD when compared with non-RA subjects. RA patients are less likely to report symptoms of angina and more likely to experience unrecognized MI and sudden cardiac death. The risk of CHD in RA patients precedes the ACR criteria-based diagnosis of RA, and the risk cannot be explained by an increased incidence of traditional CHD risk factors in RA patients.     

Levels of soluble cell adhesion molecules in patients with angiographically defined coronary atherosclerosis

Adhesion molecules on the endothelial cell membrane play an important role in the pathogenesis of atherosclerosis. Levels of soluble forms of cell adhesion molecules are reportedly elevated in patients with peripheral artery vessel disease and in patients with an atherosclerotic aorta. The present study investigated the association of serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), and soluble P-selectin (sP-selectin) with coronary heart disease (CHD) and the extent of coronary atherosclerosis, and examined the influence of serum levels of lipids, lipoproteins and apolipoproteins (apo) in subjects with (n=52, M/F:43/9) and without (controls, n=40, M/F:25/15) angiographically proven coronary atherosclerosis. After controlling for age and gender, levels of sVCAM-1 (least squares mean +/- std error: 565+/-36 ng/ml vs 540+/-41 ng/ml, ns), sICAM-1 (261+/-17ng/ml vs 247+/-19ng/ml, ns), and sP-selectin (142+/-8ng/ml vs 149+/-10 ng/ml, ns) in patients with coronary atherosclerosis were not different from those in controls, as assessed by an analysis of covariance. After also adjusting for body mass index, hypertension, diabetes mellitus, and smoking by a multiple logistic function analysis, the association of sVCAM-1, sICAM-1, and sP-selectin with CHD was still not significant. Levels of sVCAM-1, sICAM-1, and sP-selectin were also not related to the extent of coronary atherosclerosis as judged by the number of stenosed vessels. However, inverse (p<0.05) relationships were observed between sVCAMs and serum levels of HDL3-cholesterol, apo A-II, and lipoprotein containing apo A-I and A-II, between sICAMs and levels of apo A-II and Lp A-I/A-II (Lp A-I/A-II), and between sP-selectin and lipoprotein containing only apo A-I. In conclusion, serum levels of soluble VCAM-1, ICAM-1, and P-selectin were not related to CHD or the extent of coronary atherosclerosis, but were inversely related to serum levels of high-density lipoprotein-related lipoproteins.     

Differential leucocyte count and the risk of future coronary artery disease in healthy men and women: the EPIC-Norfolk Prospective Population Study

Abstract. Rana JS, Boekholdt SM, Ridker PM, Jukema JW, Luben R, Bingham SA, Day NE, Wareham NJ, Kastelein JJP, Khaw K‐T. (Academic Medical Center, Amsterdam, The Netherlands; University of Pittsburgh, Pittsburgh, PA, USA; Leiden University Medical Center, The Netherlands; and Institute of Public Health, University of Cambridge, Cambridge, UK). Differential leucocyte count and the risk of future coronary artery disease in healthy men and women: the EPIC‐Norfolk Prospective Population Study. J Intern Med 2007; 262 : 678–689. Background: We examined the relationship between granulocyte, lymphocyte and monocyte counts and risk of coronary heart disease (CHD) and cardiovascular disease (CVD) in men and women. There is paucity of data on the differential leucocyte count and its relationship with the risk of CHD and CVD. Methods: This prospective study comprised 7073 men and 9035 women who were 45–79 years of age and were residents of Norfolk. United Kingdom. Results: During an average of 8 years of follow‐up we identified 857 incident CHD events and 2581 CVD incident events. Increased total leucocyte count was associated with increased risk for both CHD and CVD. The highest quartile of granulocyte count was associated with increased risk when compared to lowest quartile for CHD (men HR 1.70 95% CI: 1.30–2.21; women HR 1.24 95% CI: 0.91–1.69) and for CVD (men HR 1.46 95% CI: 1.24–1.71; women HR 1.20 95% CI: 1.02–1.42). The association remained unchanged when the analyses were restricted to nonsmokers and when risk was assessed for every 1000 cells L^?1 increase in cell count. In multivariable models, despite adjusting for C‐reactive protein (CRP), the granulocyte count remained an independent predictor of CHD and CVD risk, especially amongst men. Lymphocyte or monocyte counts were not significantly associated with increased risk. In all analyses, additionally adjusting for CRP did not affect the results materially. Conclusions: In conclusion, we found that the higher risk for CHD and CVD associated with increased total leucocyte count seems to be accounted for by the increased granulocyte count.     

Exercise-induced silent myocardial ischemia and coronary morbidity and mortality in middle-aged men.

OBJECTIVES: We investigated the prognostic significance of exercise-induced silent myocardial ischemia in both high and low risk men with no prior coronary heart disease (CHD). BACKGROUND: Silent ischemia predicts future coronary events in patients with CHD, but there is little evidence of its prognostic significance in subjects free of CHD. METHODS: We investigated the association of silent ischemia, as defined by ST depression during and after maximal symptom-limited exercise test, with coronary risk in a population-based sample of men with no prior CHD followed for 10 years on average. RESULTS: Silent ischemia during exercise was associated with a 5.9-fold (95% CI 2.3 to 11.8) CHD mortality in smokers, 3.8-fold (95% CI 1.9 to 7.9) in hypercholesterolemic men and 4.7-fold (95% CI 2.4 to 9.1) in hypertensive men adjusting for other risk factors. The respective relative risks (RRs) of any acute coronary event were 3.0 (95% CI 1.7 to 5.1), 1.9 (95% CI 1.2 to 3.1) and 2.2 (95% CI 1.4 to 3.5). These associations were weaker in men without these risk factors. Furthermore, silent ischemia after exercise was a stronger predictor for the risk of acute coronary events and CHD death in smokers and in hypercholesterolemic and hypertensive men than in men without risk factors. CONCLUSIONS: Exercise-induced silent myocardial ischemia was a strong predictor of CHD in men with any conventional risk factor, emphasizing the importance of exercise testing to identify asymptomatic high risk men who could benefit from risk reduction and preventive measures.     

Physical activity,coronary heart disease,and inflammatory response

BACKGROUND: We sought to estimate the risk for coronary heart disease (CHD) associated with leisure time physical activity (LTPA) and work-related physical strain (WRPS) after careful adjustment for other established risk factors and to elucidate the association of physical activity with various hemostatic and inflammatory markers. METHODS: Case-control study including 312 patients aged 40 to 68 years with stable CHD (angiographically confirmed) and 479 age- and sex-matched controls. Main outcome measures were odds ratio for CHD associated with LTPA and WRPS and associations of physical activity with inflammatory and other biochemical markers after adjustment for covariates. RESULTS: LTPA showed a clear inverse association with risk of CHD. Compared with subjects who reported no summer LTPA, the odds ratio for CHD was 0.85 (95% confidence interval [CI], 0.47-1.53) in the category <1 h/wk; 0.60 (95% CI, 0.38-0.95) in the category 1-2 h/wk; and 0.39 (95% CI, 0.26-0.59) in the category >2 h/wk, after full adjustment for covariates. Similar results were obtained for winter LTPA. By contrast, there was a strong positive association between WRPS and risk of CHD. Furthermore, levels of C-reactive protein, serum amyloid A, interleukin 6, and intercellular adhesion molecule 1 were inversely and independently associated with LTPA, but not with WRPS. CONCLUSIONS: This study provides further evidence that LTPA, but not WRPS, is associated with a decreased risk of CHD, effective at even moderate levels. It further demonstrates that LTPA is associated with beneficial effects on the inflammatory response. This may represent one mechanism to explain the benefits of LTPA on coronary risk.     

Comparison of N-terminal pro-B-natriuretic peptide, C-reactive protein, and creatinine clearance for prognosis in patients with known coronary heart disease

BACKGROUND: The purpose of this study was to investigate the prognostic role of N-terminal pro-B-natriuretic peptide (NT-proBNP) serum level compared with C-reactive protein (CRP) level and creatinine clearance (CrCl) for the subsequent risk of cardiovascular events in a large cohort of patients with stable coronary heart disease (CHD). METHODS: Serum concentrations of NT-proBNP and CRP and CrCl were measured at baseline in a cohort of 1051 patients aged 30 to 70 years with CHD. The Cox proportional hazards model was used to determine the prognostic value of NT-proBNP, CRP, and CrCl on a combined cardiovascular disease (CVD) end point (fatal and nonfatal myocardial infarction and stroke). RESULTS: During follow-up (mean of 48.7 months), 95 patients (9.0%) experienced a secondary CVD event. Patients in the top quartile of the NT-proBNP distribution at baseline had a hazard ratio (HR) of 3.34 (95% confidence interval [CI], 1.74-6.45) for subsequent secondary CVD events compared with those in the bottom quartile (P for trend <.001) after controlling for age, sex, smoking status, history of diabetes mellitus, initial management of CHD, rehabilitation clinic, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and treatment with lipid-lowering drugs. For CRP, the corresponding HR was 1.76 (95% CI, 0.96-3.24) (P value for trend, .06). Patients with CrCl levels lower than 60 mL/min had an HR of 2.39 (95% CI, 1.06-5.40) compared with patients with a CrCl of 90 mL/min or higher (P for trend, .002). If all 3 markers were included simultaneously in 1 model, NT-proBNP still showed predictive ability for recurrent CVD events. CONCLUSION: N-terminal proBNP may be a clinically useful marker weeks after an acute coronary event and may provide complementary prognostic information to established risk determinants.     

Depression and medication adherence in outpatients with coronary heart disease: findings from the Heart and Soul Study

BACKGROUND: Depression leads to adverse outcomes in patients with coronary heart disease (CHD). Medication nonadherence is a potential mechanism for the increased risk of CHD events associated with depression, but it is not known whether depression is associated with medication nonadherence in outpatients with stable CHD. METHODS: We examined the association between current major depression (assessed using the Diagnostic Interview Schedule) and self-reported medication adherence in a cross-sectional study of 940 outpatients with stable CHD. RESULTS: A total of 204 participants (22%) had major depression. Twenty-eight (14%) of 204 depressed participants reported not taking their medications as prescribed compared with 40 (5%) of 736 nondepressed participants (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.7-4.7; P<.001). Twice as many depressed participants as nondepressed participants (18% vs 9%) reported forgetting to take their medications (OR, 2.4; 95% CI, 1.6-3.8; P<.001). Nine percent of depressed participants and 4% of nondepressed participants reported deciding to skip their medications (OR, 2.2; 95% CI, 1.2-4.2; P = .01). The relationship between depression and nonadherence persisted after adjustment for potential confounding variables, including age, ethnicity, education, social support, and measures of cardiac disease severity (OR, 2.2; 95% CI, 1.2-3.9; P = .009 for not taking medications as prescribed). CONCLUSIONS: Depression is associated with medication nonadherence in outpatients with CHD. Medication nonadherence may contribute to adverse cardiovascular outcomes in depressed patients.     

Soluble intercellular adhesion molecule-1 as a predictor of early adverse events in patients with chest pain compatible with myocardial ischemia

STUDY OBJECTIVE: Inflammation plays an important role in acute coronary syndromes, and some evidence indicates that patients with a more pronounced vascular inflammatory response have a poorer outcome. Soluble intercellular adhesion molecule-1 (sICAM-1) is a specific marker for vascular endothelial cell activation. The aim of this study was to investigate the prognostic value of plasma sICAM-1 levels in patients with acute chest pain compatible with myocardial ischemia. METHODS: This prospective study was conducted at 2 urban university medical centers. The study cohort consisted of 119 consecutive patients with chest pain in whom myocardial ischemia was suspected clinically at presentation. Patients with conditions that affect sICAM-1 levels were ineligible. Cardiac troponin I (cTnI), C-reactive protein, and sICAM-1 levels were assayed at presentation to the emergency department. The primary end point was the occurrence of a serious cardiac event (death, nonfatal acute myocardial infarction, coronary revascularization) in the hospital. RESULTS: Although sICAM-1 levels tended to be higher in patients with a serious cardiac event, there was no significant association. In contrast, a cTnI level greater than 0.2 ng/mL was a powerful predictor of an in-hospital serious cardiac event (odds ratio 16.3, 95% confidence interval [CI] 4.7 to 55.9; P <.0001). Soluble ICAM-1 levels of more than 260 ng/mL at presentation had a sensitivity for predicting a serious cardiac event of 63% (95% CI 46% to 81%) but a specificity of only 47% (95% CI 38% to 57%). CONCLUSION: In a heterogeneous population of patients with chest pain compatible with myocardial ischemia, elevated sICAM-1 levels are poor predictors of an individual patient suffering a serious cardiac event in the hospital.     

Red blood cell membrane concentration of cis-palmitoleic and cis-vaccenic acids and risk of coronary heart disease

Although previous studies have suggested associations between plasma palmitoleic acid and coronary heart disease (CHD) risk factors, including blood pressure, inflammation, and insulin resistance, little is known about the relation of palmitoleic acid and CHD. This ancillary study of the Physicians' Health Study was designed to examine whether red blood cell (RBC) membrane cis-palmitoleic acid and cis-vaccenic acid-2 fatty acids that can be synthesized endogenously-are associated with CHD risk. We used a risk set sampling method to prospectively select 1,000 incident CHD events and 1,000 matched controls. RBC membrane fatty acids were measured using gas chromatography. The CHD cases were ascertained using an annual follow-up questionnaire and validated by an End Point Committee through a review of the medical records. In a conditional logistic regression analysis adjusting for demographics, anthropometric, lifestyle factors, and co-morbidity, the odds ratios and 95% confidence intervals (CIs) for CHD were 1.0 (referent), 1.29 (95% CI 0.95 to 1.75), 1.08 (95% CI 0.78 to 1.51), 1.25 (95% CI 0.90 to 1.75), and 1.48 (95% CI 1.03 to 2.14) across consecutive quintiles of RBC membrane cis-palmitoleic acid (p for trend = 0.041). The odds ratio associated with each SD higher RBC membrane cis-palmitoleic acid level was 1.19 (95% CI 1.06 to 1.35) in a multivariate-adjusted model. Finally, RBC membrane cis-vaccenic acid was inversely associated with CHD risk (odds ratio 0.79, 95% CI 0.69 to 0.91, per SD increase). In conclusion, our data showed a positive association between RBC membrane cis-palmitoleic acid and CHD risk in male physicians. Furthermore, RBC membrane cis-vaccenic acid was inversely related to CHD.