Risk Of Recurrent Coronary Events Research Articles

Depression and perceived behavioral control are independent predictors of future activity and fitness after coronary syndrome events

Objective Physical inactivity increases the risk of recurrent coronary events, and both depression and perceived behavioral control (PBC) have been shown to influence levels of physical activity. However, it is not known whether depression and PBC affect activity levels independently of one another. The present study investigates whether depression and PBC exert independent effects on future exercise and fitness in patients hospitalized for coronary syndrome events. Methods Five hundred and two patients (hospitalized for myocardial infarction or newly diagnosed angina) reported their levels of depression, PBC, and current regular exercise prior to discharge from hospital, and leisure activities, fitness, regular exercise, and depression 12 months later. The ability of depression and PBC to predict patient's reported levels of activity ( n=388) and fitness ( n=361) was determined with regression analyses. Results Depression prior to discharge from hospital reliably predicted fitness ( P<.005), self-reported leisure activities ( P<.005), and taking regular exercise ( P<.005) 12 months after hospitalization for coronary syndrome events when controlling for age, gender, socio-economic status, illness severity, and reported activity prior to hospitalization. Depression at 12 months explained the variance in all outcome measures previously explained by depression at discharge, but PBC during hospitalization independently predicted leisure activities ( P<.005) and taking regular exercise ( P<.005) 12 months later. Conclusions Perceived behavioral control and depression independently predict activity and fitness in patients 12 months after hospitalization for coronary syndrome events. Consequently, interventions aiming to increase activity and fitness in these patients should take account of both patients' perceptions of control and their level of depression.

Job Strain and Risk of Recurrent Coronary Events

Job Strain and Risk of Recurrent Coronary Events

Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions

The atherogenicity theory for triglyceride-rich lipoproteins (TRLs; VLDL + intermediate density lipoprotein) generally cites the action of apolipoprotein C-III (apoC-III), a component of some TRLs, to retard their metabolism in plasma. We studied the kinetics of multiple TRL and LDL subfractions according to the content of apoC-III and apoE in 11 hypertriglyceridemic and normolipidemic persons. The liver secretes mainly two types of apoB lipoproteins: TRL with apoC-III and LDL without apoC-III. Approximately 45% of TRLs with apoC-III are secreted together with apoE. Contrary to expectation, TRLs with apoC-III but not apoE have fast catabolism, losing some or all of their apoC-III and becoming LDL. In contrast, apoE directs TRL flux toward rapid clearance, limiting LDL formation. Direct clearance of TRL with apoC-III is suppressed among particles also containing apoE. TRLs without apoC-III or apoE are a minor, slow-metabolizing precursor of LDL with little direct removal. Increased VLDL apoC-III levels are correlated with increased VLDL production rather than with slow particle turnover. Finally, hypertriglyceridemic subjects have significantly greater production of apoC-III-containing VLDL and global prolongation in residence time of all particle types. ApoE may be the key determinant of the metabolic fate of atherogenic apoC-III-containing TRLs in plasma, channeling them toward removal from the circulation and reducing the formation of LDLs, both those with apoC-III and the main type without apoC-III.

Glycoprotein Ibα Polymorphism T145M, Elevated Lipoprotein-Associated Phospholipase A2, and Hypertriglyceridemia Predict Risk for Recurrent Coronary Events in Diabetic Postinfarction Patients

To explore altered platelet function in recurrent coronary event risk among diabetic postinfarction patients, we investigated a function-altering genetic polymorphism (T145M) in the von Willebrand factor binding region of the platelet glycoprotein Ibalpha (GPIbalpha) subunit. The study comprised diabetic and nondiabetic patients of the Thrombogenic Factors and Recurrent Coronary Events postinfarction study. Cox proportional hazards multivariable modeling, adjusted for significant clinical covariates, was performed using the polymorphism and metabolic, inflammatory, and thrombogenic blood markers. Nondiabetic patients demonstrated risk for elevated lipoprotein-associated phospholipase A(2) (Lp-PLA(2)). In contrast, diabetic patients demonstrated significant and independent risk for the M allele of the T145M polymorphism (MT plus MM versus TT, hazard ratio [HR] 3.73, 95% CI 1.90-7.33, P < 0.001), hypertriglyceridemia (2.91, 1.52-5.56, P = 0.001), and elevated Lp-PLA(2) (2.78, 1.45-5.35, P = 0.002). Joint risk (one, two, or three risk factors) expressed as relative outcome rates (compared with no risk factors) were 2.4, 4.0, and 8.2, respectively. We conclude that the M allele of the T145M polymorphism of the GPIbalpha subunit predicts risk for recurrent coronary events in diabetic postinfarction patients, but not in nondiabetic postinfarction patients, supportive of an important role for platelet hyperactivation in diabetic coronary heart disease.

NAD(P)H oxidase polymorphism (C242T) and high HDL cholesterol associate with recurrent coronary events in postinfarction patients

We recently identified a subgroup of postinfarction patients at high-risk for recurrent coronary events defined by inflammation (high C-reactive protein) (CRP) and hypercholesterolemia. Within this subgroup, only elevated high-density lipoprotein cholesterol (HDL-C) from a set of metabolic, inflammatory and thrombogenic blood markers was associated with additional risk. To investigate the role of oxidative stress in this high-risk subgroup, we examined effects on risk of a polymorphism known to affect functional activity of NAD(P)H oxidase, an oxidative enzyme associated with generation of reactive oxygen species. The study population comprised non-diabetic patients of thrombogenic factors and recurrent coronary events (THROMBO) postinfarction study having complete blood marker and genotyping results (N=663) for C242T polymorphism of p22phox subunit (T allele associated with decreased activity). Cox multivariable regression, adjusted for significant clinical covariates, was used to assess within-subgroup risk associated with blood markers and polymorphism. In addition to elevated HDL-C (hazard ratio, 95% CI and p-value; 2.62, 1.05–6.55 and 0.039), significant independent risk was found for C242T (CC versus CT plus TT: 3.14, 1.34–7.35 and 0.0084). We conclude that oxidative stress plays a significant role in establishment of risk for recurrent coronary events in a high-risk subgroup of postinfarction patients defined by inflammation and hypercholesterolemia.

Polymorphism in the Angiotensinogen Gene, Hypertension, and Ethnic Differences in the Risk of Recurrent Coronary Events

The M235T mutation of the human angiotensinogen gene has been shown to be associated with elevated circulating angiotensinogen concentrations and essential hypertension. The frequencies of the 235T allele are significantly different in black and white subjects. We analyzed the independent contribution of the angiotensinogen M235T mutation to the development of recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) in a cohort of 916 black (n=145) and white (n=771) postmyocardial infarction patients who were prospectively studied during an average follow-up of 28 months. The frequency of the 235T allele was significantly higher among black (82%) than among white (44%) patients (P<0.001). There was no evidence for Hardy-Weinberg disequilibrium. During follow-up, 41 cardiac events (28%) occurred in blacks and 197 (26%) in whites (P=0.49). Multivariate Cox proportional hazards regression analysis demonstrated that 235T homozygosity was independently associated with increased risk of coronary events among black (hazard ratio: 2.37; P=0.04) but not white (hazard ratio: 0.93; P=0.68) patients, with a significant ethnic-related interaction effect (P for the difference=0.04). Among hypertensive black patients, the TT genotype was associated with a 3.3-fold (P=0.02) increase in the risk of coronary events. Our findings suggest that homozygosity for the 235T mutation in the angiotensinogen gene is an independent risk factor for coronary events in black postmyocardial infarction patients. The presence of hypertension significantly augments the risk associated with this genetic mutation.

Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: A factor analysis approach

Background Numerous inflammatory mediators such as C-reactive protein (CRP), fibrinogen, interleukin-18 (IL-18), and inter-cellular adhesion molecule-1 (ICAM-1) have been proposed for risk stratification in acute coronary syndrome (ACS) patients. However, interactions between these markers have made it difficult to assess their true role in risk prediction. Factor analysis is a multivariable statistical technique that reduces a large number of intercorrelated variables to a smaller set of independent clusters, underlining physiological relationships. The aim of this study was to investigate, using factor analysis, a clustering of pro-inflammatory markers, anti-inflammatory cytokines such as interleukin-10 (IL-10) and HDL cholesterol, and to determine their role in prediction of risk of recurrent coronary events in ACS patients. Methods We assessed 320 consecutive patients (236 men; 67 years; IQ 58–74 years) admitted with ACS. The composite of cardiac death and re-hospitalization with non-fatal myocardial infarction, or unstable angina, was the pre-specified study end-point. Serum CRP, fibrinogen, HDL cholesterol, IL-10, IL-18 and ICAM-1 levels were measured at study entry. We assessed independent predictors of the combined end-point during a 1-year follow-up using multiple logistic regression analysis. Results Factor analysis identified three clusters which were arbitrarily interpreted as (1) a “systemic inflammation” cluster with positive loadings of CRP and fibrinogen, (2) a “local inflammation–endothelial dysfunction” cluster with positive loadings of IL-18 and ICAM-1 and (3) an “anti-inflammation” cluster comprising IL-10 and HDL cholesterol. Only the “anti-inflammation” cluster was a significant predictor (OR 0.66, 95% CI: 0.49–0.89) of adverse cardiac events during a 1-year follow-up and remained significant (OR 0.65, 95% CI: 0.48–0.88) in a multivariate model that included all three factors. Conclusions Although inflammatory markers such as CRP predict future cardiovascular events in ACS patients, when all inflammatory mediators are taken into account in a prospective analysis of risk, markers reflecting anti-inflammatory mechanisms are better prognostic markers.

High Lipoprotein-Associated Phospholipase A2 Is a Risk Factor for Recurrent Coronary Events in Postinfarction Patients

Recent studies demonstrate that lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk factor for cardiovascular disease presumably deriving from generation of proinflammatory and proatherogenic species through its hydrolytic activity on lipoprotein-associated phospholipids. The goal of this study was to assess the relationship of Lp-PLA2 with a set of thrombogenic, lipid, inflammatory, and metabolic blood markers and to determine whether plasma Lp-PLA2 is a risk factor for recurrent coronary events in postinfarction patients. Factor analysis on the set of blood markers and Lp-PLA2 was performed for 766 patients of the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) postinfarction study. Recurrent coronary event risk was assessed as a function of blood marker concentrations and Lp-PLA2 by Cox proportional hazards multivariable regression adjusted for significant clinical covariates. Factor analysis revealed that Lp-PLA2 was associated with one factor dominated by cholesterol and apolipoprotein B and another factor dominated by HDL-cholesterol and triglycerides, with little association with an inflammatory factor dominated by C-reactive protein. Multivariable analysis demonstrated as significant and independent predictors of risk of secondary coronary events only apolipoprotein B in a model without Lp-PLA2 (hazard ratio, 1.66; 95% confidence interval, 1.14-2.40) and only Lp-PLA2 in a model with Lp-PLA2 included [1.90 (1.31-2.75)]. Lp-PLA2 is a significant and independent predictor of risk for recurrent coronary events in postinfarction patients, and Lp-PLA2 is related to both hypercholesterolemia and high triglyceride-low HDL dyslipidemia in this study population.

Platelet activation predicts recurrent ischemic events after percutaneous coronary angioplasty: A 6 months prospective study

Introduction An increasing amount of evidence indicates that platelet reactivity, despite a standard anti-thrombotic therapy, is a potential risk factor for recurrent myocardial ischemia in patients with coronary artery disease. We now hypothesize that this condition, measured by collagen–epinephrine (CEPI) or collagen–ADP (CADP) closure times (CT) by Platelet Function Analyzer (PFA-100), may predict the recurrence of coronary events after percutaneous coronary intervention (PCI). Materials and methods CEPI and CADP-CT were measured 30 ± 8 h after PCI in 175 consecutive patients admitted with a diagnosis of stable angina ( n = 94) or acute coronary syndromes ( n = 81) and prospectively followed up for a mean period of 6 months. We stratified the patients in accordance to both the CEPI-CT (<or> 190 s), reflecting the intensity of cycloxygenase inhibition by aspirin and the distribution into quartiles for CADP-CT. Results CEPI-CT < 190 s as well as CADP-CT < 82 s were associated with a higher rate of clinical recurrence (hazard ratio 8.5, p < 0.001 and 22.9, p < 0.001, respectively). Multivariate analysis after adjustment for other risk factors confirmed that the lowest CADP-CT quartile significantly correlates with the risk of recurrent coronary events (hazard ratio 36.5, p < 0.01), as well as CEPI-CT < 190 s (hazard ratio 6.7, p = 0.01). Conclusions An enhanced platelet function after PCI when measured under high shear rates by PFA-100 is an independent predictor of a worst clinical outcome, even during a short term follow-up and may help in patients risk stratification.

Elevated HDL is a risk factor for recurrent coronary events in a subgroup of non-diabetic postinfarction patients with hypercholesterolemia and inflammation

Recent studies demonstrate important roles for inflammation in development of atherosclerosis with current attention focusing on interactions of inflammation with traditional lipoprotein risk factors. Since the nature of such relationships is largely unknown, we sought to investigate interactions of inflammation with hyperlipidemia in generating cardiovascular risk in a way that would allow recognition of such interactions whether anticipated or not. Thus, we searched for subgroups at high risk for recurrent coronary events in 767 non-diabetic postinfarction patients using an exploratory three-dimensional graphical screening technique with previously established factor analysis-derived inflammatory and lipoprotein-related factors. Results indicated a high-risk patient subgroup defined by factor interaction that was best characterized clinically by high levels of C-reactive protein (CRP) and total cholesterol. Kaplan–Meier and Cox multivariate analysis confirmed high-risk. Additionally, within-subgroup risk related to metabolic, inflammatory, and thrombogenic blood markers was assessed using Cox analysis with results showing only elevated HDL as a significant and independent predictor of risk with hazard ratio, 2.24 (95% CI; 1.12, 4.49; p = 0.023). We conclude that in non-diabetic postinfarction patients, elevated HDL is predictive of risk of recurrent coronary events within a subgroup of patients characterized by simultaneous elevations in serum CRP and total cholesterol.

Serum glucose and triglyceride determine high-risk subgroups in non-diabetic postinfarction patients

A strategy was developed to identify subgroups at high risk for recurrent coronary events in non-diabetic postinfarction patients as a function of metabolic, inflammatory, and thrombogenic blood markers. A graphical screening technique for presumptively identifying high-risk subgroups from outcome prevalence maps was devised that was equally sensitive for all values of risk factors in contrast to traditional approaches where risk is presumed for the highest or the lowest values. Traditional statistical analysis confirms high risk in identified subgroups. Serum glucose and triglyceride served as bivariate search domain. Results demonstrated three high-risk subgroups. One was characterized as pre-diabetic; another as metabolic syndrome-enriched; and the third, with unexpectedly high risk, as normoglycemic and modestly hypertriglyceridemic. Within-subgroup risk as determined by Cox proportional hazards model gave for odds ratios and 95 percentile confidence intervals: glucose, 2.49 (1.17–5.33) in pre-diabetic; PAI-1, 3.95 (1.81–8.61) in metabolic syndrome-enriched; and BMI, 2.79 (1.17–6.63) and fibrinogen, 2.79 (1.29–6.04) in normoglycemic, modestly hypertriglyceridemic patients. We conclude that the graphical approach holds promise in screening for high-risk patient subgroups. Finding different within-subgroup predictors of risk underscores the notion of context-dependent risk, an observation that may be relevant for determining optimal use of emerging risk factors.

Atherosclerotic Risk Genotypes and Recurrent Coronary Events After Myocardial Infarction

The association of a group of prespecified atherosclerotic risk genotypes with recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) was investigated in a cohort of 1,008 patients after infarction during an average follow-up of 28 months. We used a carrier-ship approach with time-dependent survivorship analysis to evaluate the average risk of each carried genotype. Contrary to expectation, the hazard ratio for recurrent coronary events per carried versus noncarried genotype was 0.89 (95% confidence interval 0.80 to 0.99, p = 0.03) after adjustment for relevant genetic, clinical, and environmental covariates. This hazard ratio, derived from the 7 prespecified genotypes, indicated an average 11% reduction in the risk of recurrent coronary events per carried versus noncarried genotype. At 1 year after hospital discharge, the cumulative probability of recurrent coronary events was 26% in those who carried < or =1, 20% for those with 2 to 4, and 13% for those with > or =5 of these genotypes (p = 0.02). This unexpected risk reversal is a likely consequence of changes in the mix of risk factors in pre- and postinfarction populations. In conclusion, this under appreciated, population-based, risk-reversal phenomenon may explain the inconsistent associations of genetic risk factors with outcome events in previous reports involving coronary populations with different risk attributes.

Elevated Preprocedural High-Sensitivity C-Reactive Protein Levels are Associated With Neointimal Hyperplasia and Restenosis Development After Successful Coronary Artery Stenting

Recent data indicate that an elevated serum level of high-sensitivity C-reactive protein (hs-CRP) predicts the risk of recurrent coronary events, and that statin therapy decreases the risk of coronary events. This study assessed the relationship between the pre-procedural hs-CRP level and in-stent neointimal hyperplasia (NIH) after stenting and the effects of statins on the relationship between restenosis after stenting and the serum hs-CRP levels of patients with coronary artery disease. This study included 100 patients who underwent stent implantation for angiographically significant stenosis. Patients were divided into a normal C-reactive protein (CRP) group (<0.5 mg/dl, n=59) and elevated CRP group (>or=0.5 mg/dl, n=41). All patients underwent angiographic and intravascular ultrasound follow-up at 6 months. The baseline CRP level was 0.29+/-0.08 mg/dl in the normal CRP group and 2.90+/-2.31 mg/dl in the elevated CRP group. The NIH cross-sectional area (CSA) in the minimal lumen CSA at follow-up was significantly larger in the elevated CRP group compared with the normal CRP group (1.9+/-1.3 mm2 vs 3.0+/-1.5 mm2, p=0.001). A significant positive correlation was found between pre-interventional CRP level and NIH area (r=0.52, p<0.001). In patients with normal CRP, an association between statin therapy and restenosis was not observed. However, when the analysis was confined to patients with elevated CRP, statin therapy significantly reduced the restenosis rate (20% vs 37.5%, p=0.031). In the normal CRP group, the intra-stent neointimal area at 6 months was not different between the non-statin and statin groups (2.2+/-1.4 mm2 vs 1.8+/-1.1 mm2). However, in the elevated CRP group, statin therapy significantly decreased the neointimal area at 6-month follow-up (3.6+/-1.7 mm2 vs 2.4+/-1.3 mm2, p<0.001). Measuring the pre-interventional hs-CRP level may help predict the development of restenosis after stenting and statin therapy will significantly reduce the restenosis rate in patients with an elevated hs-CRP.

Effect of atorvastatin on risk of recurrent cardiovascular events after an acute coronary syndrome associated with high soluble CD40 ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study

Study Question: Patients with acute coronary syndrome (ACS) have elevated plasma levels of the proinflammatory, prothrombotic cytokine CD40 ligand (sCD40L). The present analysis examined the relationship between sCD40L and the risk of recurrent cardiovascular events soon after an ACS in the MIRACL study and tested whether the clinical benefit from statin therapy was related to a reduction in proinflammatory and prothrombotic stimuli associated with sCD40L. Methods: The investigators measured sCD40L in subjects with an ACS enrolled in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects were randomized in this double-blind trial either to atorvastatin 80 mg/d or placebo for 16 weeks. Results: Plasma CD40L was measured from 2908 (94%) of 3086 subjects at baseline and 2352 (76%) subjects at 16 weeks. Odds ratios (ORs) and 95% CIs from logistic regression models assessed the risk of recurrent cardiovascular events over 16 weeks (death, nonfatal myocardial infarction, cardiac arrest, and worsening angina requiring rehospitalization) in the placebo group from baseline sCD40L and the effect of atorvastatin on the risk associated with CD40L in all subjects. The effects of atorvastatin on plasma concentrations of CD40L were assessed by Wilcoxon tests. There was a threshold effect, with only high sCD40L (>90th centile) being a risk factor for a recurrent cardiovascular event (OR 1.86, 95% CI 1.25–2.77). This risk was abolished by atorvastatin (OR 1.09, 95% CI 0.69–1.76), which reduced the risk by 48%. Atorvastatin had only a modest effect on sCD40L (p=0.08). Conclusions: The investigators state that, in patients with ACS, atorvastatin abrogated the risk of recurrent cardiovascular events associated with high sCD40L. Perspective: Patients presenting with ACS with highly elevated sCD40L have a higher risk of recurrent coronary events. In this setting, intensive statin therapy may reduce the risk of recurrent events associated with high sCD40L levels without affecting plasma concentrations of this cytokine. The present study points to anti-inflammatory and antithrombotic actions of statins as an additional mechanism of benefit after ACSs. DM

Apolipoprotein B determines risk for recurrent coronary events in postinfarction patients with metabolic syndrome

The adult treatment panel III (ATP III) of the National Cholesterol Education Program recognizes metabolic syndrome (MS) as a secondary target for risk-reduction therapy given the well-known increase in risk of cardiovascular disease (CVD) by all MS components. We investigated potential CVD risk arising from 17 laboratory variables in postinfarction patients with MS by identifying such patients from the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) study using slightly modified ATP III criteria for MS. This gave 272 patients with MS out of a total of 766 postinfarction patients without history of diabetes. Comparison between non-MS and MS patients using Kaplan–Meier analysis revealed no difference in outcome between groups. Additionally, a proportional hazards model applied to dichotomized laboratory parameters demonstrated only apoB as a significant predictor of risk for recurrent coronary events in MS patients with hazard ratio, 1.97 (95% CI; 1.08, 3.60; P < 0.05). We conclude that there is no difference in outcomes between non-MS and MS postinfarction patients; that apoB is significantly associated with risk for recurrent coronary events in postinfarction patients with MS; that further studies would be needed to recommend the routine determination of apoB in these patient groups.

Association of elevated homocysteine levels with a higher risk of recurrent coronary events and mortality in patients with acute myocardial infarction

Background: Despite the prothrombotic and proinflammatory effects associated with elevated homocysteine levels, only limited data exist regarding the effect of homocysteine levels on outcome of patients with acute myocardial infarction. Methods: Homocysteine levels were determined within 24 hours of presentation in 157 consecutive patients with acute myocardial infarction. Patients were allocated to 2 groups: those with homocysteine levels of 2.7 mg/L (20 μmol/L) or more (n=22 [14%]) and those with homocysteine levels of less than 2.7 mg/L (n=135 [86%]). Results: Female and diabetic patients had significantly lower homocysteine levels than males (P<.01) and non-diabetic patients (P=.005), respectively, with no significant correlation with age (r=0.07, P=.42) or other risk factors. Patients with homocysteine levels greater than or equal to 2.7 mg/L and less than 2.7 mg/L did not differ significantly regarding extent of coronary artery disease as reflected by prevalence of multivessel disease (54% vs 61%; P=.87), and their in-hospital course. However, in a mean tSD follow-up of 30±10 months, patients with homocysteine levels greater than or equal to 2.7 mg/L had a higher incidence of recurrent coronary events (36% vs 17%; P=.04) and death (18% vs 5%; P<.05). Homocysteine levels greater than or equal to 2.7 mg/L remain a significant determinant of recurrent coronary event and/or death after controlling for potential cofounders by multivariate analysis (odds ratio, 3.8; 95% confidence interval, 1.3-11.0). Conclusions: In patients with acute myocardial infarction, elevated homocysteine levels are associated with a higher risk of recurrent coronary events and death, independent of other risk factors and the extent of coronary artery disease.

Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease

Apolipoprotein C-III (apoC-III) is a marker of triglyceride (TG)-rich lipoproteins, which are often increased in metabolic syndrome (MS). The T-455C polymorphism in the insulin-responsive element of the APOC3 gene influences TG and apoC-III levels. To evaluate the contribution of apoC-III levels and T-455C polymorphisms in the coronary artery disease (CAD) risk of MS patients, we studied 873 patients, 549 with CAD and 251 with normal coronary arteries. Patients were classified also as having or not having MS (MS, n = 270; MS-free, n = 603). Lipids, insulin, apolipoprotein levels, and APOC3 T-455C genotypes were evaluated. ApoC-III levels were significantly increased in MS patients, and the probability of having MS was correlated with increasing quartiles of apoC-III levels. MS patients with CAD had significantly higher apoC-III levels than did CAD-free MS patients. The carriership for the -455C variant multiplied the probability of CAD in MS in an allele-specific way and was associated with increased apoC-III and TG levels. Obesity was less frequent in MS carriers of the -455C allele than in MS noncarriers (21.6% vs. 34.8%, P < 0.05). In conclusion, apoC-III-rich lipoprotein metabolism and the APOC3 polymorphism have relevant impacts on the CAD risk of MS patents.

Association of elevated homocysteine levels with a higher risk of recurrent coronary events and mortality in patients with acute myocardial infarction.

Despite the prothrombotic and proinflammatory effects associated with elevated homocysteine levels, only limited data exist regarding the effect of homocysteine levels on outcome of patients with acute myocardial infarction. Homocysteine levels were determined within 24 hours of presentation in 157 consecutive patients with acute myocardial infarction. Patients were allocated to 2 groups: those with homocysteine levels of 2.7 mg/L (20 micro mol/L) or more (n = 22 [14%]) and those with homocysteine levels of less than 2.7 mg/L (n = 135 [86%]). Female and diabetic patients had significantly lower homocysteine levels than males (P<.01) and nondiabetic patients (P =.005), respectively, with no significant correlation with age (r = 0.07, P =.42) or other risk factors. Patients with homocysteine levels greater than or equal to 2.7 mg/L and less than 2.7 mg/L did not differ significantly regarding extent of coronary artery disease as reflected by prevalence of multivessel disease (54% vs 61%; P =.87), and their in-hospital course. However, in a mean +/-SD follow-up of 30 +/- 10 months, patients with homocysteine levels greater than or equal to 2.7 mg/L had a higher incidence of recurrent coronary events (36% vs 17%; P =.04) and death (18% vs 5%; P<.05). Homocysteine levels greater than or equal to 2.7 mg/L remain a significant determinant of recurrent coronary event and/or death after controlling for potential cofounders by multivariate analysis (odds ratio, 3.8; 95% confidence interval, 1.3-11.0). In patients with acute myocardial infarction, elevated homocysteine levels are associated with a higher risk of recurrent coronary events and death, independent of other risk factors and the extent of coronary artery disease.

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.

Simvastatin reduces plasma concentration of high-sensitivity C-reactive protein in type 2 diabetic patients with hyperlipidemia

High-sensitivity C-reactive protein (hs-CRP) is positively associated with the prevalence of coronary artery disease by epidemiologic data. Prospective studies indicate that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduced the plasma hs-CRP concentration and the risk of recurrent coronary events after myocardial infarction. Type 2 diabetes is associated with high mortality risk of coronary heart disease and this high risk may be involved in the inflammatory factors. We have therefore conducted a prospective study to assess whether simvastatin can rapidly reduce the plasma hs-CRP concentration in type 2 diabetic patients with hyperlipidemia. Seventeen type 2 diabetic patients with hyperlipidemia were enrolled in the study after 6 weeks on a lipid-lowering diet. Fourteen patients completed the study, taking simvastatin 20 mg daily for 8 weeks. Fasting blood samples were collected from each patient before and after 8-week administration of simvastatin. In response to 8-week administration of simvastatin, hs-CRP levels significantly decreased from 0.312±0.057 to 0.193±0.045 mg/dl ( P<.01). Plasma LDL cholesterol also decreased significantly from 130±9 to 74±3 mg/dl ( P=.001). This study shows that plasma hs-CRP concentration can be reduced by 8-week administration of simvastatin in type 2 diabetic patients with hyperlipidemia.