Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease

CONTEXT: Free fatty acids (FFAs) are associated with several cardiovascular risk factors and exert harmful effects on the myocardium. OBJECTIVE: The aim of our study was to elucidate the relationship between FFAs and mortality in subjects who underwent coronary angiography. DESIGN, SETTING, AND PARTICIPANTS: Ludwigshafen Risk and Cardiovascular Health is a prospective cohort study of Caucasians who had undergone coronary angiography at baseline (1997-2000). During a median time of follow-up of 5.38 yr, 513 deaths had occurred among 3315 study participants with measured FFAs. MAIN OUTCOME MEASURE: Hazard ratios for mortality according to FFA levels were measured. RESULTS: At the fourth quartile of FFAs, fully adjusted hazard ratios for death from any cause and cardiovascular causes were 1.58 (P = 0.002) and 1.83 (P = 0.001), respectively. In persons with angiographic coronary artery disease (CAD), stable CAD, and unstable CAD, the predictive value of FFAs was similar to that in the entire cohort, but the association did not attain statistical significance in persons without CAD analyzed separately. FFA levels were not related to the presence of angiographic CAD but were elevated in subjects with unstable CAD, compared with probands with stable CAD. Furthermore, FFAs increased with the severity of heart failure and were positively correlated with N-terminal pro-B-type natriuretic peptide (P < 0.001). CONCLUSIONS: FFA levels independently predict all-cause and cardiovascular mortality in subjects with angiographic CAD. A possible diagnostic use of FFAs warrants further studies, but our results may underline the importance of therapeutic approaches to influence FFA metabolism.     

Cross-sectional associations of resistin, coronary heart disease, and insulin resistance

CONTEXT: Recently, resistin was found to be present in atherosclerotic lesions in apoE(-/-) mice. Resistin may be associated with inflammation and atherosclerosis in humans; however, the role of resistin in human disease remains controversial. OBJECTIVE: This study assesses cross-sectional relationships of resistin with coronary heart disease (CHD). DESIGN, SETTING, AND PARTICIPANTS: Blood samples from the third examination of the Strong Heart Study (SHS)--the largest study of CHD in American Indians--were used. Cases who had suffered previous myocardial infarction (n = 100) were selected randomly from the three SHS sites and matched for study site and sex with controls who had no history of cardiovascular disease (CHD or stroke) (n = 100). MAIN OUTCOME MEASURE: Resistin levels by enzyme-linked immunosorbent assay method in cases and controls was the main outcome measure. RESULTS: Resistin levels were higher in cases than controls [median (interquartile range): 3.4 (2.5-4.7) vs. 2.8 (2.1-4.0) ng/ml; P = 0.003] and had univariate correlations with age (Spearman r = 0.21; P < 0.002), fasting insulin (r = 0.21; P = 0.003), insulin resistance by homeostasis model (r = 0.22; P = 0.04), albumin to creatinine ratio (r = 0.19; P = 0.01), and fibrinogen (r = 0.34; P < 0.0001). Cases were more likely to have diabetes (cases 67%; controls 41%; P < 0.0001) but had similar body mass index (cases 31.4 +/- 5.4; controls 30.7 +/- 6.3; P = 0.85). Resistin levels were higher in participants with established nephropathy (albumin to creatinine ratio >300 mg/g, n = 26) compared with those with normo- (n = 122) or microalbuminuria (n = 42). In multivariate analysis, nephropathy (P = 0.0013) but not previous myocardial infarction (P = 0.12) was significantly associated with resistin. CONCLUSIONS: Resistin is not independently associated with CHD. Resistin is elevated in survivors of myocardial infarction; however, this reflects a novel association of raised resistin with diabetic nephropathy.     

Plasma resistin levels and risk of myocardial infarction and ischemic stroke

CONTEXT: Resistin is a hormone that has been linked to insulin resistance, inflammatory processes, and coronary heart disease in case-control studies; however, prospective data on the association between plasma resistin levels and future risk of cardiovascular disease are lacking. OBJECTIVE: The objective of the study was to investigate the association between plasma resistin levels and risk of future myocardial infarction (MI) and ischemic stroke (IS) in a large prospective cohort. METHODS: We investigated the association between plasma resistin levels and risk of MI and IS in a case-cohort design among 26,490 middle-aged subjects from the European Investigation into Cancer and Nutrition-Potsdam Study without history of MI or stroke at time of blood draw. Plasma resistin levels were measured in baseline blood samples of 139 individuals who developed MI, 97 who developed IS, and 817 individuals who remained free of cardiovascular events during a mean follow-up of 6 yr. RESULTS: After multivariable adjustment for established cardiovascular risk factors including C-reactive protein, individuals in the highest compared with the lowest quartile of plasma resistin levels had a significantly increased risk of MI (relative risk 2.09; 95% confidence interval 1.01-4.31; P for trend = 0.01). In contrast, plasma resistin levels were not significantly associated with risk of IS (relative risk 0.94; 95% confidence interval 0.51-1.73; P for trend = 0.88). CONCLUSION: Our data suggest that high plasma resistin levels are associated with an increased risk of MI but not with risk of IS. Further studies are needed to evaluate the predictive value of plasma resistin levels for cardiovascular disease.     

Resistin, acute coronary syndrome and prognosis results from the AtheroGene study

OBJECTIVE: Resistin, an adipocyte and macrophage derived cytokine, causes insulin resistance and glucose intolerance. We investigated the impact of resistin as a diagnostic marker in patients with acute coronary syndrome and its prognostic value for future cardiovascular events. METHODS: Resistin levels were determined in 1153 patients with stable angina (SAP), 380 patients with unstable angina, 278 patients with non-ST-elevation myocardial infarction (NSTEMI) and 111 patients with ST-elevation myocardial infarction (STEMI). All patients have been followed up for a median follow-up of 2.6 years. During follow-up, 70 patients died from cardiovascular causes. RESULTS: Compared to SAP, resistin levels (5.1 ng/mL in SAP) were elevated in patients with angina at rest (5.89 ng/mL, P=0.001), in patients with NSTEMI (6.00 ng/mL, P<0.001), and in patients with STEMI (5.98 ng/mL, P<0.001). Resistin levels rose at 3-6h after chest pain onset (5.46 ng/mL), persisted elevated among those individuals presenting between 6 and 12h after chest pain onset (5.57 ng/mL) and peaked in individuals presenting more than 12h after chest pain onset (5.74 ng/mL). An increase of one standard deviation of resistin levels was associated with a 1.22-fold (95% CI 1.04-1.43; P=0.02) risk for future fatal cardiovascular events in a model adjusted for risk factors and clinical and therapeutic variables. When adjustment for renal function was applied, this association lost its statistical significance. CONCLUSIONS: Resistin levels are elevated in patients presenting with unstable angina, NSTEMI and STEMI and might play a role as a diagnostic marker. In addition, systemic resistin level is moderately associated with future cardiovascular death in patients with documented coronary artery disease.     

血清抵抗素水平与动脉粥样硬化的相关性研究

目的探讨血清抵抗素与动脉粥样硬化的关系及其可能在糖尿病大血管并发症中所起的作用。方法病例选自2004年9月至2005年3月北京军区总医院的行冠状动脉造影的患者共88例,分为单纯冠心病组、糖尿病合并冠心病组、单纯糖尿病组以及正常对照组。受试者空腹采血,行生化检查及血清抵抗素、高敏C反应蛋白(hs-CRP)、可溶性肿瘤坏死因子受体2(sTNF-R2)的测定。结果各组患者血清抵抗素以及hs-CRP、sTNF-R2均高于正常对照组(P<0·05);抵抗素与sTNF-R2呈正相关(r=0·24,P=0·025),而与hs-CRP无显著相关性(P=0·613);多元回归分析显示,性别(b=0·194,P=0·029)及冠状动脉病变支数(b=0·155,P=0·001)是影响血清抵抗素水平的因素;随着冠脉病变支数的增加,血清抵抗素呈增高的趋势(P=0·004)。结论冠心病患者,特别是糖尿病合并冠心病患者,血清抵抗素水平增高;冠脉病变支数是影响血清抵抗素的重要因素;血清抵抗素水平与炎症标志呈正相关,提示抵抗素可能作为炎症因子在动脉粥样硬化以及糖尿病大血管并发症的发病机制中发挥作用。     

Serum resistin as a biological marker for coronary artery disease and restenosis in type 2 diabetic patients.

BACKGROUND: Resistin is an adipocyte-secreted hormone. The relationship between circulating resistin concentrations and atherosclerotic coronary artery disease (CAD) in type 2 diabetic patients, if any, remains poorly understood. Serum resistin concentrations were investigated in type 2 diabetic patients with CAD (DMCAD), and compared with the concentrations in diabetics patients without CAD (diabetes mellitus, DM). Whether resistin levels are associated with increased restenosis rates in diabetic patients with CAD after successful coronary stenting was also investigated. METHODS AND RESULTS: Fasting serum resistin, adiponectin, and leptin concentrations were measured in 45 DMCAD patients and 47 DM controls. The percutaneous coronary intervention study included 70 DMCAD patients, who underwent elective and successful coronary bare metal stent (BMS) implantation for the treatment of de novo lesions. Serum resistin concentrations were higher in the DMCAD patients than in the DM controls (5.75+/-3.21 vs 2.53+/-2.47 ng/ml, mean +/- SEM, p<0.001), and these differences were persistent regardless of age or body mass index. Insulin resistance indices, as assessed via homeostasis model assessment (HOMA-IR) correlated significantly with resistin concentrations (r=0.4, p<0.001). Resistin was an independent factor, and was associated with DMCAD in the multivariate analysis. In the percutaneous coronary intervention study, HOMA-IR was not associated with subsequent restenosis rates after BMS implantation in DMCAD patients. Pre-procedural serum resistin concentrations were higher in restenosis group than in the patients without restenosis. CONCLUSIONS: Serum resistin may prove to be a useful biological marker for CAD and restenosis in patients with type 2 DM.     

Increased resistin gene and protein expression in human abdominal adipose tissue

Resistin, a novel signalling molecule isolated in mice has been suggested to be the putative hormone thought to link obesity with type 2 diabetes. The aim of this study was to examine resistin protein expression in human adipose tissue depots and resistin secretion in isolated adipose cells, to characterize resistin expression in human adipose tissue. Both resistin mRNA and protein expression were analysed from human adipose tissue (n = 5 adipose tissue samples: abdominal subcutaneous (Sc) n = 19, abdominal omental adipose tissue (Om) n = 10, thigh n = 9, breast n = 7). Resistin protein expression levels were similar in both the abdominal Sc and Om adipose tissue depots, and expression in abdominal fat depots were increased compared with thigh (p < 0.001) and breast tissue depots (p < 0.001). These findings were consistent with the mRNA expression studies. Resistin was secreted from both pre-adipocytes and adipocytes cells. Thus, resistin resides within isolated adipose cells and is expressed and secreted in human adipose tissue. In conclusion, this study confirms the expression of resistin in human adipose tissue and increased expression in abdominal fat, this suggests a potential role in linking central obesity to type 2 diabetes and/or cardiovascular disease.     

High plasma resistin level is associated with enhanced highly sensitive C-reactive protein and leukocytes

OBJECTIVES: Resistin is a newly described hormone with a suggested role in insulin resistance. In humans, inflammatory cells seem to be the major source of resistin. The aim of this study was to find out whether plasma resistin concentration associates with carotid artery atherosclerosis and the risk factors of atherosclerosis. METHODS: Plasma resistin concentrations were measured in 525 Finnish middle-aged subjects among our population-based cohort. Intima-media thickness was measured from the internal carotid artery, the bifurcation enlargement, and the common carotid artery. RESULTS: Among all the subjects, the median resistin concentration was 7.07 ng/ml (interquartile range, 5.82-8.84), women having higher levels than men (P < 0.001) with median values of 7.56 ng/ml (6.18-9.19) and 6.67 ng/ml (5.63-8.31), respectively. Resistin level correlated negatively with mean intima-media thickness, internal carotid artery, and common carotid artery, but the association did not remain significant after adjustments. Plasma resistin concentration was associated positively with leukocytes (P < 0.001), highly sensitive C-reactive protein (P = 0.009), and IGF binding protein 1 (P < 0.001), but not with plasma insulin or glucose levels in analysis of covariance after adjustments for age, sex, and body mass index. CONCLUSIONS: The results imply that inflammatory factors are more important in the determination of plasma resistin concentration than plasma insulin or glucose values. Resistin is associated with proatherogenic inflammatory markers but not independently with early atherosclerosis.     

Adiponectin and mortality in patients undergoing coronary angiography

CONTEXT: The adipokine adiponectin has been suggested to protect against coronary artery disease (CAD). However, studies addressing the association between adiponectin and mortality are sparse. OBJECTIVE: The objective of the study was to elucidate the relationship between adiponectin and mortality. DESIGN, SETTING, AND PARTICIPANTS: Adiponectin was determined in 2473 persons with and 673 persons without angiographic CAD. During a mean follow-up period of 5.45 yr, 427 persons with CAD and 55 persons without CAD died. MAIN OUTCOME MEASURE: Hazard ratios for mortality according to adiponectin levels were measured. RESULTS: Adiponectin was positively related to female gender, age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, homocysteine, and N-terminal pro-B-type natriuretic peptide. It was inversely related to glomerular filtration rate, body mass index, and triglycerides and was low in diabetes mellitus and CAD. An increase of 1 sd in adiponectin was associated with unadjusted and fully adjusted hazard ratios for death from any cause of 1.31 [95% confidence interval (CI) 1.20-1.42] and 1.22 (95% CI 1.12-1.34), and for death from cardiovascular causes of 1.32 (95% CI 1.19-1.45) and 1.23 (95% CI 1.11-1.37), respectively. In angiographic CAD, stable CAD, and unstable CAD, the predictive value of adiponectin was similar to that in the entire cohort, but it did not attain statistical significance in persons without angiographic CAD. Adiponectin was also positively related to the risk of death from noncardiovascular causes. CONCLUSIONS: Despite the common view about adiponectin as a protective molecule in cardiovascular disease, high adiponectin independently predicts all-cause, cardiovascular, and noncardiovascular mortality in individuals with CAD.     

Serum creatinine predicts mortality in patients with peripheral artery disease: influence of diabetes and hypertension

BACKGROUND: Patients with renal insufficiency tend to suffer from advanced atherosclerosis and exhibit a reduced life expectancy. We investigated the association of renal impairment, traditional cardiovascular risk factors and all-cause mortality in patients with symptomatic peripheral artery disease (PAD). METHODS: We studied 515 patients with advanced PAD (intermittent claudication, n = 410; critical ischemia, n = 105). Cardiovascular risk profile and calculated glomerular filtration rate (GFR) were obtained at baseline and patients were followed for median 21 months (interquartile range 12 to 25) for mortality. RESULTS: Sixty-five patients (13%) died. Cumulative survival rates at 6, 12, and 24 months were 97%, 95%, and 89%, respectively. Adjusted hazard ratios for mortality according to decreasing quartiles of GFR were 1.2, 2.5, and 5.9 compared to the highest quartile (P < 0.001). The association between renal impairment and mortality was independent of diabetes and hypertension, suggesting that decreased GFR adds to the prognostic value of traditional cardiovascular risk factors. CONCLUSION: Renal impairment is associated with an increased risk for mortality in patients with advanced peripheral artery disease, irrespective of the coincidence of arterial hypertension and diabetes mellitus. This suggests that impaired renal function exerts an unfavorable effect on patient's outcome, independently of these cardiovascular and renal risk factors.     

Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease.

It is a matter of controversy as to whether uric acid is an independent predictor of mortality in patients with coronary artery disease (CAD) or whether it represents only an indirect marker of adverse outcome by reflecting the association between uric acid and other cardiovascular risk factors. Therefore, we studied the influence of uric acid levels on mortality in patients with CAD. In 1,017 patients with angiographically proven CAD, classic risk factors and uric acid levels were determined at enrollment. A follow-up over a median of 2.2 years (maximum 3.1) was performed. Death from all causes was defined as an end point of the study. In CAD patients with uric acid levels <303 micromol/L (5.1 mg/dl) (lowest quartile) compared with those with uric acid levels >433 micromol/L (7.1 mg/dl) (highest quartile), the mortality rate increased from 3.4% to 17.1% (fivefold increase). After adjustment for age, both sexes demonstrated an increased risk for death with increasing uric acid levels (female patients: hazard ratio [HR] 1.30, 95% confidence intervals [CI] 1.14 to 1.49, p < or = 0.001; male patients: HR 1.39 [95% CI 1.21 to 1.59], p < or = 0.001). In multivariate Cox regression analysis performed with 12 variables that influence overall mortality-including diuretic use-elevated levels of uric acid demonstrated an independent, significant positive relation to overall mortality (HR 1.23 [95% CI 1.11 to 1.36], p <0.001) in patients with CAD. Thus, uric acid is an independent predictor of mortality in patients with CAD.     

Do associations with C-reactive protein and extent of coronary artery disease account for the increased cardiovascular risk of renal insufficiency?

OBJECTIVES: We sought to determine whether the association of higher C-reactive protein levels (CRP) and more extensive coronary artery disease (CAD) explains the high cardiovascular risk of renal insufficiency (RI). BACKGROUND: Renal insufficiency and renal failure (RF) have been associated with increased cardiovascular risk in several studies, and it has been suggested that this association may be due to higher CRP levels and greater extent of CAD. To what extent CRP or severity of CAD explains this risk is uncertain. METHODS: A total of 1,484 patients without myocardial infarction (MI) undergoing angiography were entered and followed for 3.0 +/- 1.6 years; RI and RF were defined as estimated glomerular filtration rates (GFR) of 30 to 60 and <30 ml/min; CRP was measured by immunoassay and > or = 1.0 mg/dl defined as elevated. A CAD score was determined by extent and severity of angiographic disease. Multivariate Cox regressions were performed using seven standard risk factors, homocysteine, GFR, CRP, and CAD score. RESULTS: Mean age was 64 years, and 67% were men; CAD was absent in 24%, mild in 11%, and severe (> or =70% stenosis) in 60%; CRP and CAD scores increased with declining renal function (median CRP: 1.2, 1.4, 2.2 mg/dl, p < 0.001 and CAD score: 8.1, 8.7, 9.3, p = 0.008 for no-RI, RI, and RF). During follow-up, 208 patients (15%) died or had nonfatal MI. Unadjusted hazard ratio (HR) for death/MI was 2.3 for RI and 5.1 for RF (p < 0.0001). Adjustment for CRP (HR, 2.2, 4.5), CAD score (HR, 2.1, 5.1), and all other risk factors (HR, 1.7, 4.5) had minimal or modest impact on RI and RF risk; HR increased to 5.4 (p < 0.001) for presence of both elevated CRP and RI/RF. CONCLUSIONS: Renal insufficiency, CRP, and angiographic CAD, although correlated, are largely independent predictors of cardiovascular risk, suggesting the importance of both inflammation and as yet undefined RI-related risk factors.     

Association of uric acid with mortality in patients with stable coronary artery disease

ObjectiveThe association between uric acid and cardiovascular disease is poorly studied. We undertook this study to assess whether uric acid level predicts clinical outcome in patients with stable coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI).Materials/MethodsThis study included 8149 patients with stable CAD who underwent PCI. Uric acid was measured before angiography. The primary end point was 1-year mortality. Quartiles of quartiles of uric acid were: 1.49 to < 5.49 mg/dl (1st quartile; n=2032 patients), 5.49 to < 6.40 mg/dl (2nd quartile; n=1981 patients), 6.40 to < 7.50 mg/dl (3rd quartile; n=2093 patients) and 7.50 to 21.90 mg/dl (4th quartile; n=2043 patients).ResultsThere were 196 deaths during the 1-year follow-up. The numbers of deaths (Kaplan-Meier estimates) according to uric acid quartiles were: 35 deaths (1.8%) in the 1st quartile, 30 deaths (1.6%) in the 2nd quartile, 45 deaths (2.2%) in the 3rd quartile and 86 deaths (4.3%) in the 4th quartile (unadjusted hazard ratio [HR]=1.60, 95% confidence interval [CI] 1.38-1.86, P < 0.001 for each standard deviation [SD] increase in the logarithmic scale). After adjustment for traditional cardiovascular risk factors, renal function and inflammatory status, the association between uric acid and 1-year mortality remained significant (adjusted HR=1.26, 95% CI 1.07-1.48; P=0.005 for each standard deviation increase in the logarithmic scale). Uric acid improved predictivity of the multivariable model regarding mortality (P=0.040).ConclusionsElevated level of uric acid is an independent predictor of 1-year mortality in patients with stable CAD treated with PCI.     

Relationship between plasma resistin concentrations, inflammatory chemokines, and components of the metabolic syndrome in adults

Recent data suggest that resistin, an adipocyte-derived cytokine, has a putative role in inflammatory processes and metabolic derangements. In vitro data suggest that resistin stimulates the production of inflammatory chemokines, yet the relationship in vivo is largely unknown. The purpose of this study was to determine if a relationship exists between plasma resistin concentrations, plasma inflammatory chemokine aged concentrations (ie, monocyte chemoattractant protein 1 [MCP-1] and epithelial neutrophil activator 78 [ENA-78]), and components of the metabolic syndrome in nondiabetic subjects without known cardiovascular disease (CVD). Plasma samples were obtained from nondiabetic subjects (N = 123) aged 18 to 55 years without known CVD or CVD risk equivalents. The presence of the metabolic syndrome was assessed using consensus guidelines. Fasting plasma resistin, MCP-1, ENA-78, and high-sensitivity C-reactive protein (hs-CRP) concentrations were analyzed. The study population consisted of 67.5% women and 68.3% Caucasians (mean age = 44 +/- 7 years and mean body mass index = 33.3 +/- 6 kg/m(2)). The metabolic syndrome was present in 46.3% of study participants. Resistin concentrations were significantly correlated with white blood cell count (r = 0.326, P < .001), hs-CRP concentrations (r = 0.293, P = .005), MCP-1 concentrations (r = 0.251, P = .005), body mass index (r = 0.193, P = .033), and high-density lipoprotein cholesterol (r = -0.182, P = .044). Resistin concentrations were 1.21 times higher in subjects with the metabolic syndrome compared with those without the metabolic syndrome (P = .003). In stepwise regression analysis, white blood cell count (P < .001) and MCP-1 concentrations (P = .002) were significantly associated with resistin concentrations, independent of hs-CRP, sex, body mass index, presence of the metabolic syndrome, and high-density lipoprotein cholesterol. Data from our cross-sectional study demonstrate that plasma resistin concentrations are associated with circulating chemokine markers of inflammation, namely, MCP-1, and white blood cell count in nondiabetic adults without CVD. Future studies examining the causal relationship between plasma resistin concentrations, chemokine markers of inflammation, CVD, and diabetes are warranted.     

Mild renal insufficiency is associated with angiographic coronary artery disease in women

BACKGROUND: Mild renal insufficiency is associated with an increased risk for cardiovascular events in women with coronary artery disease (CAD). However, the relationship between mild renal insufficiency and atherosclerotic CAD in women is not known. Methods and Results- Women with chest pain who were referred for coronary angiography in the NHLBI Women's Ischemia Syndrome Evaluation (WISE) study underwent quantitative coronary angiography, blood measurements of creatinine, lipids, and homocysteine, and assessment of CAD risk factors. Fifty-six women had mild renal insufficiency (serum creatinine 1.2 to 1.9 mg/dL), and 728 had normal renal function (creatinine <1.2 mg/dL). Creatinine correlated with angiographic CAD severity score (r=0.11, P<0.004) and maximum coronary artery stenosis (r=0.11, P<0.003). Compared with women with normal renal function, those with mild renal insufficiency were more likely to have significant angiographic CAD (>/=50% diameter stenosis in >/=1 coronary artery) (61% versus 37%; P<0.001) and CAD in multiple vessels (P<0.001 for association) and had greater maximum percent diameter coronary stenosis (59+/-35% versus 38+/-36%; P<0.001). Mild renal insufficiency was associated with significant angiographic CAD independent of age and risk factors (OR=1.9, 95%CI=1.1 to 3.5). After controlling for homocysteine in 509 women, mild renal insufficiency remained predictive of CAD (OR=3.2, 95%CI=1.4 to 7.2). CONCLUSIONS: In women with chest pain, mild renal insufficiency is an independent predictor of significant angiographic CAD. Mildly increased serum creatinine is probably a marker for unmeasured proatherogenic factors.     

Independent and incremental value of coronary artery calcium for predicting the extent of angiographic coronary artery disease: comparison with cardiac risk factors and radionuclide perfusion imaging.

OBJECTIVES: The study was done to test the ability to predict the extent of angiographically determined coronary artery disease (CAD) by quantification of coronary calcium using electron-beam computed tomography (EBCT) and to compare it with more conventional parameters for delineating the angiographic extent of CAD, that is, cardiovascular risk factors and radionuclide single-photon emission computed tomography (SPECT). BACKGROUND: The angiographic extent of CAD is a powerful predictor of subsequent events. Use of EBCT may be able to define it by virtue of its ability to determine plaque burden. METHODS: We examined 308 patients presenting with suspected but not previously known CAD who underwent selective coronary angiography. As measures of the angiographic extent of CAD, coronary artery greater even 20 (CAGE > or =20) and CAGE > or =50 scores represented the total number of coronary segments with > or =20% or > or =50% stenoses, respectively. The EBCT-derived total calcium scores were obtained in 291 patients, risk factors as defined by the National Cholesterol Education Program in 239 patients, and SPECT scans in 136 patients. RESULTS: Using multiple linear regression analysis, total calcium scores were better independent predictors of both CAGE > or =20 and CAGE > or =50 scores than either a SPECT-derived radionuclide perfusion score or the risk factors age, male gender and ratio of total/high-density lipoprotein (HDL) cholesterol. The association between EBCT and angiographic scores remained highly significant after excluding the influence of all interrelated risk factors and SPECT variables (r = 0.65; p < 0.001 for CAGE > or =20 scores, r = 0.50; p < 0.001 for CAGE > or =50 scores). CONCLUSIONS: Coronary calcium predicts the angiographic extent of CAD in symptomatic patients and provides independent and incremental information to the more conventional clinical parameters derived from SPECT or risk assessment.     

The relation of C-reactive protein levels to total and cardiovascular mortality in older U.S. women

PURPOSE: To determine whether serum C-reactive protein levels, a sensitive indicator of inflammation, are associated with the risk of cardiovascular mortality among older women. METHODS: We conducted a case-cohort study within the Study of Osteoporotic Fractures, a population-based study involving 9,704 women aged > or = 65 years from four U.S. centers. We randomly selected 400 women from the entire cohort plus an additional random sample of 92 women from the 1,125 women in the cohort who had died during the first 6 years of follow-up. Baseline serum C-reactive protein levels were measured using a high-sensitivity immunoassay. Cause-specific mortality was ascertained by review of death certificates and hospitalization records. Multivariable Cox proportional hazards regression was used to determine the association between C-reactive protein levels and cardiovascular mortality. RESULTS: During 6 years of follow-up, 150 of the 492 women died, including 52 who died of cardiovascular disease. After adjusting for potential confounders, women with C-reactive protein levels in the highest quartile (>3.0 mg/L) had a 8.0-fold (95% confidence interval [CI]: 2.2 to 29) greater risk of cardiovascular mortality than those in the lowest quartile (< or = 1.0 mg/L). The association remained strong in women who did not smoke or take estrogen, and when early deaths were excluded. Women who smoked and whose C-reactive protein levels were above the first quartile had a very high risk of cardiovascular mortality (relative risk [RR] = 13; 95% CI: 3.4 to 47). C-reactive protein levels were not associated with noncardiovascular mortality (RR = 0.92; 95% CI: 0.4 to 2.1). CONCLUSION: C-reactive protein level was an independent predictor of cardiovascular mortality in older women.     

Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health--National Heart, Lung, and Blood Institute sponsored Women's Ischemia Syndrome Evaluation

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described. OBJECTIVE: The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. METHODS: A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (> or = 701 pg/ml), testosterone (> or = 30.9 ng/dl), or free testosterone (> or = 4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55). RESULTS: Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates. CONCLUSION: Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events.     

Serum gamma-glutamyl transferase and mortality in persons undergoing coronary angiography—The Ludwigshafen Risk and Cardiovascular Health Study

ObjectiveSerum gamma-glutamyl transferase (GGT) seems to be a predictor for coronary artery disease (CAD). The objective of this study was to elucidate the relationship between GGT and total as well as cardiovascular mortality.MethodsSerum levels of GGT were determined in 2556 subjects with and 699 subjects without angiographic evidence of CAD in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.ResultsSerum GGT was positively associated with male gender, alcohol consumption and markers of the metabolic syndrome (triglycerides, blood pressure, waist circumference and insulin resistance). It was positively related to aspartate aminotransferase, alanine aminotransferase, C-reactive protein, interleukin-6, and negatively related to glutathione and increased age. During a mean follow-up period of 7.75 years, 754 subjects died. Compared with subjects in the lowest quartile of GGT, the unadjusted hazard ratios (95% CI) for all-cause death were 1.2 (0.9–1.5), 1.4 (1.1–1.8) and 1.9 (1.5–2.3), respectively, in other GGT quartiles. Hazard ratios (CI) for death from cardiovascular causes were 1.4 (1.0–2.0), 1.8 (1.4–2.5) and 2.2 (1.6–2.9). After adjustment for age, gender and cardiovascular risk factors GGT remained a significant predictor for total and cardiovascular mortality. In angiographic CAD the predictive value of GGT was also significant and similar to that in the entire cohort.ConclusionSerum GGT is predictive of all-cause and cardiovascular mortality in individuals with CAD independently of other cardiovascular risk factors.     

Alanine to serine polymorphism at position 986 of the calcium-sensing receptor associated with coronary heart disease, myocardial infarction, all-cause, and cardiovascular mortality

BACKGROUND: Disorders of calcium homeostasis have been implicated in atherosclerosis. The calcium-sensing receptor (CASR) is crucial to the regulation of calcium metabolism. An alanine (A) to serine (S) polymorphism at codon 986 (A986S) of the CASR gene has been associated with higher calcium and osteoporosis; the association with coronary artery disease (CAD) has not been studied. METHODS AND RESULTS: We investigated this polymorphism in individuals with CAD (n = 2561), including survivors of myocardial infarction (MI) (n = 1358) compared to 698 controls without angiographic CAD. Compared to AA homozygotes, the prevalence of CAD [multivariate odds ratio 1.25; 95% confidence interval (CI) 1.02-1.54] and previous MI (multivariate odds ratio 1.33; 95% CI 1.06-1.68) was increased in carriers of at least one S-allele. With each S-allele, the prevalence of CAD and MI increased 1.22-fold (95% CI 1.02-1.47) and 1.30-fold (95% CI 1.06-1.60), respectively. Fully adjusted hazard ratios for total and cardiovascular mortality per one S-allele were 1.24 (95% CI 1.05-1.46) and 1.38 (95% CI 1.13-1.67), respectively. In carriers of at least one S-allele, the adjusted hazard ratios for all-cause and cardiovascular death were 1.25 (95% CI 1.04-1.51) and 1.48 (95% CI 1.18-1.86), respectively. These associations were independent of cardiovascular risk factors, calcium and phosphate. The S-allele was associated with higher calcium (P < 0.001) and PTH (P < 0.02), and lower phosphate (P < 0.003) in CAD patients and controls. CONCLUSION: Serine at position 986 of CASR may be an independent genetic predictor of angiographic CAD, previous MI, and cardiovascular mortality.