Usefulness of noninvasive estimate of pulmonary vascular resistance to predict mortality, heart failure, and adverse cardiovascular events in Patients With stable coronary artery disease (from the Heart and Soul Study)

Pulmonary vascular resistance (PVR) is an important hemodynamic variable that affects prognosis and therapy in a wide range of cardiovascular and pulmonary conditions. We sought to determine whether a noninvasive estimate of PVR predicts adverse outcomes in patients with stable coronary artery disease. Using Doppler echocardiography we measured the estimated PVR (defined as the ratio of the tricuspid regurgitant velocity [TRV] to the velocity-time integral [VTI] of the right ventricular outflow tract [RVOT]) in 795 ambulatory patients with stable coronary artery disease. Participants were categorized by quartiles of the TRV/VTI RVOT ratio. Hazard ratios (HRs) and 95% confidence intervals were calculated for all-cause mortality, heart failure hospitalization, and adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or stroke). After 4.3 years of follow-up there were 161 deaths, 44 deaths from cardiovascular causes, 103 heart failure hospitalizations, and 120 adverse cardiovascular events. Compared with patients in the lowest TRV/VTI RVOT quartile, those in the highest quartile were at increased risk of all-cause mortality (unadjusted HR 1.8, 95% confidence interval 1.3 to 2.5), heart failure hospitalization (unadjusted HR 2.9, 95% confidence interval 2.0 to 4.3), and adverse cardiovascular events (unadjusted HR 2.0, 95% confidence interval 1.4 to 2.9). After multivariate adjustment, patients in the highest quartile were at increased risk of heart failure hospitalizations (adjusted HR 2.5, 95% confidence interval 1.3 to 4.7). In conclusion, a noninvasive estimate of PVR (TRV/VTI RVOT ratio) predicts mortality, heart failure hospitalization, and adverse cardiovascular events in patients with stable coronary artery disease.     

Relation Between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People With Coronary Disease

BACKGROUND: Higher levels of red blood cell distribution width (RDW) may be associated with adverse outcomes in patients with heart failure. We examined the association between RDW and the risk of all-cause mortality and adverse cardiovascular outcomes in a population of people with coronary disease who were free of heart failure at baseline. METHODS AND RESULTS: We performed a post hoc analysis of data from the Cholesterol and Recurrent Events study. Baseline RDW was measured in 4111 participants who were randomized to receive pravastatin 40 mg daily or placebo and followed for a median of 59.7 months. We used Cox proportional hazards models to examine the association between RDW and adverse clinical outcomes. During nearly 60 months of follow-up, 376 participants died. A significant association was noted between baseline RDW level and the adjusted risk of all-cause mortality (hazard ratio per percent increase in RDW, 1.14; 95% confidence interval, 1.05 to 1.24). After categorization based on quartile of baseline RDW and further adjustment for hematocrit and other cardiovascular risk factors, a graded independent relation between RDW and death was observed (P for trend=0.001). For instance, participants with RDW in the highest quartile had an adjusted hazard ratio for death of 1.78 (95% confidence interval, 1.28 to 2.47) compared with those in the lowest quartile. Higher levels of RDW were also associated with increased risk of coronary death/nonfatal myocardial infarction, new symptomatic heart failure, and stroke. CONCLUSIONS: We found a graded independent relation between higher levels of RDW and the risk of death and cardiovascular events in people with prior myocardial infarction but no symptomatic heart failure at baseline.     

Pericardial fat inflammation correlates with coronary artery disease

Objectives

Serum gamma-glutamyltransferase (γ-GT) predicts incident cardiovascular disease and mortality. The present study examined whether γ-GT also is associated with prognosis in patients with stable coronary heart disease.

Methods and results

This study included 1152 participants (aged 30–70 years at baseline) of an in-patient rehabilitation programme after acute coronary syndrome, recruited in two rehabilitation clinics in Germany in the years 1999–2000 (KAROLA study). Until year 8 follow-up, 147 participants had experienced a non-fatal or fatal secondary cardiovascular disease event. Confounder-adjusted Cox proportional hazards models revealed an increase in risk for secondary events over ascending γ-GT quartiles, with hazard ratios (95% confidence interval) of 1.21 (0.72–2.03), 1.32 (0.80–2.16) and 1.75 (1.08–2.83) for the 2nd, 3rd and 4th in reference to the lowest quartile (P_trend = 0.024). The association with all-cause mortality examined as a secondary outcome was slightly stronger (hazard ratio of 4th quartile: 1.97 [1.15–3.36]; P_trend = 0.017).

Conclusions

In patients with stable coronary heart disease, serum γ-GT was associated with prognosis independent of a variety of established risk markers. The association appeared similar to that reported for primary cardiovascular disease, which should motivate additional studies of its clinical utility in cardiovascular patient care.     

Usefulness of adiponectin as a predictor of all cause mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Substantial evidence points to a protective role of adiponectin against atherosclerosis and cardiovascular (CV) disease. However, in the setting of an acute myocardial infarction (AMI), the role of adiponectin has not previously been studied. Consequently, the aim of this study was to investigate the prognostic role of adiponectin after AMI in a large population of patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. A total of 735 consecutive patients with ST-segment elevation myocardial infarction admitted to a single high-volume invasive heart center and treated with primary percutaneous coronary intervention from September 2006 to December 2008 were included. Blood samples were drawn immediately before the invasive procedure. Plasma adiponectin was measured using a validated immunoassay. End points were all-cause mortality, CV mortality, and admission for new AMI or heart failure. The median follow-up time was 27 months (interquartile range 22 to 33). Patients with high adiponectin (quartile 4) had increased mortality compared to patients with low adiponectin (quartiles 1 to 3) (log-rank p <0.001). After adjustment for conventional risk factors (age, gender, smoking, hypertension, hypercholesterolemia, diabetes, body mass index, C-reactive protein, peak troponin I, creatinine, estimated glomerular filtration rate, previous AMI, multivessel disease, complex lesions, left anterior descending coronary artery lesion, and symptom-to-balloon time) by Cox regression analysis, high adiponectin remained an independent predictor of all-cause mortality (hazard ratio 2.1, 95% confidence interval 1.3 to 3.2, p = 0.001) and CV mortality (hazard ratio 2.6, 95% confidence interval 1.5 to 4.5, p = 0.001). In conclusion, increased plasma adiponectin independently predicts all-cause and CV mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.     

Elevated plasma free fatty acids predict sudden cardiac death: a 6.85-year follow-up of 3315 patients after coronary angiography.

AIMS: Sudden cardiac death (SCD) is the most common fatal cardiovascular event. Free fatty acids (FFAs) exert several harmful effects on the myocardium and may therefore contribute to SCD. We examined whether fasting FFA predict SCD in patients who had undergone coronary angiography. METHODS AND RESULTS: FFAs were measured at baseline (1997-2000) in 3315 patients scheduled for coronary angiography. Angiographic coronary artery disease was found in 2231 study participants. After a median time of follow-up of 6.85 years, 165 SCD occurred in the entire study population. In a Cox proportional hazards model, the unadjusted hazard ratio (HR) for SCD in the fourth when compared with the first FFA quartile was 2.95 (95% CI 1.84-4.73; P < 0.001). After adjustment for common and emerging cardiovascular risk factors, the HR remained significant at 1.76 (1.03-3.00; P = 0.038). High FFA levels were also significantly associated with all-cause and cardiovascular mortality, even after exclusion of patients with SCD. CONCLUSION: Our study shows that elevated plasma FFAs are an independent risk factor for future SCD in patients referred to coronary angiography. These results may suggest that modulation of myocardial fatty acid uptake and/or metabolism are a possible target of treatment, but it still remains to be clarified whether high FFA levels are a cause or a consequence of pathological processes that underlie the association between FFA and SCD.     

The prognostic utility of D-dimer and fibrin monomer at long-term follow-up after hospitalization with coronary chest pain

D-dimer and fibrin monomer both reflect a prothrombotic potential. There are limited data available comparing these two markers of activated coagulation in a prospective manner in an unselected patient population presenting to the emergency department with chest pain. In addition, their role in risk stratification in patients with acute coronary syndrome is still under evaluation. Therefore, we wanted to assess the prognostic value of these markers with respect to long-term all-cause mortality in 871 patients admitted to the emergency department. Blood samples were obtained immediately following admission. After a follow-up period of 24 months, 123 patients had died. In the univariate analysis, both D-dimer and fibrin monomer predicted all-cause mortality within 2 years with an odds ratio of 7.78 (95% confidence interval, 3.95-15.33) and 4.19 (95% confidence interval, 2.42-7.28), respectively, in the highest quartile (Q4) compared with the lowest quartile (Q1). However, in the multivariable logistic regression model for death within 2 years, the odds ratio of D-dimer and fibrin monomer was 1.80 (95% confidence interval, 0.81 to 3.97) and 1.04 (95% confidence interval, 0.53 to 2.04) in Q4 compared with Q1, respectively, and added no prognostic information above and beyond age, known coronary heart disease, B-type natriuretic peptide and the index diagnoses of ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction and unstable angina pectoris. In an unselected patient population hospitalized with chest pain and potential acute coronary syndrome, neither D-dimer nor fibrin monomer provided complementary prognostic information to established risk determinants during long-term follow-up.     

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.     

High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke

BACKGROUND: Inflammatory markers have been associated with ischemic stroke risk and prognosis after cardiac events. Their relationship to prognosis after stroke is unsettled. METHODS: A population-based study of stroke risk factors in 467 patients with first ischemic stroke was undertaken to determine whether levels of high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A(2) (Lp-PLA2) predict risk of stroke recurrence, other vascular events, and death. RESULTS: Levels of Lp-PLA2 and hs-CRP were weakly correlated (r = 0.09; P = .045). High-sensitivity CRP, but not Lp-PLA2, was associated with stroke severity. After adjusting for age, sex, race and ethnicity, history of coronary artery disease, diabetes mellitus, hypertension, hyperlipidemia, atrial fibrillation, smoking, and hs-CRP level, compared with the lowest quartile of Lp-PLA2, those in the highest quartile had an increased risk of recurrent stroke (adjusted hazard ratio, 2.08; 95% confidence interval, 1.04-4.18) and of the combined outcome of recurrent stroke, MI, or vascular death (adjusted hazard ratio, 1.86; 95% confidence interval, 1.01-3.42). After adjusting for confounders, hs-CRP was not associated with risk of recurrent stroke or recurrent stroke, myocardial infarction, or vascular death but was associated with risk of death (adjusted hazard ratio, 2.11; 95% confidence interval, 1.18-3.75). CONCLUSIONS: Inflammatory markers are associated with prognosis after first ischemic stroke and may offer complementary information. Lipoprotein-associated phospholipase A(2) may be a stronger predictor of recurrent stroke risk. Levels of hs-CRP, an acute-phase reactant, increase with stroke severity and may be associated with mortality to a greater degree than recurrence.     

Renal function and risk of myocardial infarction in an elderly population: the Rotterdam Study

BACKGROUND: Renal insufficiency is a risk factor for cardiovascular disease in patients with renal disease or coronary heart disease; however, it is unknown whether renal function is an independent predictor of cardiovascular disease in the general population. METHODS: We investigated whether the level of renal function, estimated by glomerular filtration rate, was associated with the risk of incident myocardial infarction among 4484 apparently healthy subjects in the Rotterdam Study (mean age, 69.6 years). We estimated the glomerular filtration rate by Cockcroft-Gault and abbreviated modification of diet in renal disease equations and used Cox regression analysis to estimate hazard ratios adjusted for cardiovascular risk factors, atherosclerosis, and medication use. RESULTS: During the follow-up period (mean, 8.6 years), 218 subjects (4.9%) had a myocardial infarction. A 10 mL/min per 1.73 m(2) decrease in glomerular filtration rate was associated with a 32% increased risk of myocardial infarction (P<.001). Compared with subjects in the fourth quartile, the multivariate-adjusted hazard ratios for the risk of myocardial infarction increased from 1.64 (95% confidence interval [CI], 1.03-2.59) in the third quartile to 1.94 (95% CI, 1.21-3.10) in the second quartile and 3.06 (95% CI, 1.80-5.19) in the quartile with the lowest glomerular filtration rate estimated by the Cockcroft-Gault equation. Using the abbreviated modification of diet in renal disease equation, the risk estimates for the third to first quartiles were 1.34 (95% CI, 0.89-2.01), 1.66 (95% CI, 1.14-2.49), and 1.90 (95% CI, 1.25-2.90), respectively. CONCLUSIONS: The present study shows that renal function is a graded and independent predictor of the development of myocardial infarction in an elderly population. Early detection of decreased renal function may identify subjects who are at heightened risk of coronary heart disease.     

Prognostic value of uric acid in patients with acute coronary syndromes

The association between uric acid and cardiovascular disease is incompletely understood. In particular, the prognostic value of uric acid in patients with acute coronary syndromes who undergo percutaneous coronary intervention has not been studied. This study included 5,124 patients with acute coronary syndromes who underwent percutaneous coronary intervention: 1,629 with acute ST-segment elevation myocardial infarction, 1,332 with acute non-ST-segment elevation myocardial infarction, and 2,163 with unstable angina. The primary end point was 1-year mortality. Patients were divided into quartiles according to uric acid level as follows: quartile 1, 1.3 to <5.3 mg/dl; quartile 2, 5.3 to <6.3 mg/dl; quartile 3, 6.3 to <7.5 mg/dl; and quartile 4, 7.5 to 18.4 mg/dl. There were 450 deaths during follow-up: 80 deaths in quartile 1, 77deaths in quartile 2, 72 deaths in quartile 3, and 221 deaths in quartile 4 of uric acid (Kaplan-Meier estimates of 1-year mortality 6.4%, 6.2%, 5.6%, and 17.4%, respectively; unadjusted hazard ratio 3.05, 95% confidence interval 2.54 to 3.67, p <0.001 for fourth vs first quartile of uric acid). After adjustment for traditional cardiovascular risk factors, renal function, and inflammatory status, the association between uric acid and mortality remained significant, with a 12% increase in the adjusted risk for 1-year mortality for every 1 mg/dl increase in the uric acid level. Uric acid improved the discriminatory power of the predictive model regarding 1-year mortality (absolute integrated discrimination improvement 0.008, p = 0.005). In conclusion, elevated levels of uric acid are an independent predictor of 1-year mortality across the whole spectrum of patients with acute coronary syndromes treated with percutaneous coronary intervention.     

Predictive value of elevated white blood cell count in patients with preexisting coronary heart disease: the Bezafibrate Infarction Prevention Study

BACKGROUND: Inflammation is implicated in the pathogenesis of atherosclerosis and acute coronary syndromes. White blood cell (WBC) count increases during infections and inflammatory illnesses and has been shown to predict coronary heart disease (CHD) independent of traditional cardiovascular risk factors. This apparent association may reflect a relationship between the WBC count and other coronary risk factors. Studies in patients with CHD are scarce and give conflicting results. The aim of the present study was to investigate the association between WBC count and subsequent coronary events and total mortality in a large cohort of patients with CHD. METHODS: We evaluated the relationship between WBC count and 6-year risk of coronary events and mortality in a large cohort of patients with chronic CHD who were enrolled in a secondary prevention study of bezafibrate. RESULTS: In univariate analysis, WBC count was associated with an elevated 6-year risk of myocardial infarction, cardiac death, and total mortality. On multivariate adjustment, the positive association with risk of myocardial infarction and cardiac death was eliminated, but WBC count remained predictive of total mortality: relative risk, 1.47; 95% confidence interval, 1.13 to 1.92, in the upper tertile of WBC count (as compared with the lowest). For every 1000/ microL increase in WBC count, risk of total death increased by 6% (relative risk, 1.06; 95% confidence interval, 1.03-1.10). CONCLUSIONS: Elevated WBC count in patients with CHD was associated with higher long-term risk of all-cause mortality. This excess risk of mortality was not due to cardiac causes.     

Relations between QRS|T angle, cardiac risk factors, and mortality in the third National Health and Nutrition Examination Survey (NHANES III)

On the surface electrocardiogram, an abnormally wide QRS|T angle reflects changes in the regional action potential duration profiles and in the direction of the repolarization sequence, which is thought to increase the risk of ventricular arrhythmia. We investigated the relation between an abnormal QRS|T angle and mortality in a nationally representative sample of subjects without clinically evident heart disease. We studied 7,052 participants ≥40 years old in the third National Health and Nutrition Examination Survey with 12-lead electrocardiograms. Those with self-reported or electrocardiographic evidence of a previous myocardial infarction, QRS duration of ≥120 ms, or history of heart failure were excluded. Borderline and abnormal spatial QRS|T angles were defined according to gender-specific 75th and 95th percentiles of frequency distributions. All-cause (1,093 women and 1,191 men) and cardiovascular (462 women and 455 men) mortality during the 14-year period was assessed through linkage with the National Death Index. On multivariate analyses, an abnormal spatial QRS|T angle was associated with an increased hazard ratio (HR) for cardiovascular mortality in women (HR 1.82, 95% confidence interval 1.05 to 3.14) and men (HR 2.21, 95% confidence interval 1.32 to 3.68). Also, the multivariate adjusted HR for all-cause mortality associated with an abnormal QRS|T angle was 1.30 (95% confidence interval 0.95 to 1.78) for women and 1.87 (95% confidence interval 1.29 to 2.7) for men. A borderline QRS|T angle was not associated with an increased risk of all-cause or cardiovascular mortality. In conclusion, an abnormal QRS|T angle, as measured on a 12-lead electrocardiogram, was associated with an increased risk of cardiovascular and all-cause mortality in this population-based sample without known heart disease.     

A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women

We examined the relationship of maturity-onset clinical diabetes mellitus with the subsequent incidence of coronary heart disease, stroke, total cardiovascular mortality, and all-cause mortality in a cohort of 116,177 US women who were 30 to 55 years of age and free of known coronary heart disease, stroke, and cancer in 1976. During 8 years of follow-up (889 255 person-years), we identified 338 nonfatal myocardial infarctions, 111 coronary deaths, 259 strokes, 238 cardiovascular deaths, and 1349 deaths from all causes. Diabetes was associated with a markedly increased risk of nonfatal myocardial infarction and fatal coronary heart disease (age-adjusted relative risk [RR] = 6.7; 95% confidence interval [CI], 5.3 to 8.4), ischemic stroke (RR = 5.4; 95% CI, 3.3 to 9.0), total cardiovascular mortality (RR = 6.3; 95% CI, 4.6 to 8.6), and all-cause mortality (RR = 3.0; 95% CI, 2.5 to 3.7). A major independent effect of diabetes persisted in multivariate analyses after simultaneous control for other known coronary risk factors (for these end points, RR [95% CI] = 3.1 [2.3 to 4.2], 3.0 [1.6 to 5.7], 3.0 [1.9 to 4.8], and 1.9 [1.4 to 2.4], respectively). The absolute excess coronary risk due to diabetes was greater in the presence of other risk factors, including cigarette smoking, hypertension, and obesity. These prospective data indicate that maturity-onset clinical diabetes is a strong determinant of coronary heart disease, ischemic stroke, and cardiovascular mortality among middle-aged women. The adverse effect of diabetes is amplified in the presence of other cardiovascular risk factors, many of which are modifiable.     

The effect of radial pulse spectrum on the risk of major adverse cardiovascular events in patients with type 2 diabetes

Radial pulse spectrum has been shown to correlate with coronary stenosis in patients with type 2 diabetes mellitus (T2DM). In academia, it has not been demonstrated that the radial artery pulse spectrum is an independent risk factor for major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and all-cause mortality. The primary objective of this study is to assess the risk of MACE, in patients with T2DM and to determine if an increase in MACE would be associated with a first harmonic (C1) increase in the radial artery pulse. 1972 consecutive patients with T2DM were enrolled. All subjects received measurements of radial pulse waves at baseline. Harmonic analysis of radial pressure wave was performed. The hazard ratios for MACE and its 95% confident interval were estimated using Cox proportional hazard model. The follow-up period lasted for one year. MACE was detected in 232 (11.8%) of those with T2DM. The log-rank test demonstrated that the cumulative incidence of patients with C1 above 0.96 was greater than those with C1 bellow 0.96. Comparing the patients with C1 smaller than first quartile to the patients with C1 greater than third quartile, higher C1 increased the cardiovascular risks as follows: MACE (Hazard ratio,1.93; 95% CI,1.31–2.86), stroke (Hazard ratio, 1.61; 95% CI, 0.90–2.90), myocardial infarction (Hazard ratio, 2.23; 95% CI, 1.33–3.74). The risk for the composite MACE increased continuously as C1 increased (P?<?0.001 for trend). The hazard ratio and trend for all-cause mortality were not significant. Increased C1 resulted in increased risk for nonfatal stroke, and nonfatal myocardial infarction among patients with T2DM. Our results indicate that the degree of C1 is a risk factor for nonfatal MACE. Therefore, the radial pulse spectrum could identify patients with T2DM at high risk of nonfatal MACE.     

Apolipoprotein B and Non-HDL Cholesterol Better Reflect Residual Risk Than LDL Cholesterol in Statin-Treated Patients

BackgroundIn cholesterol guidelines, low-density lipoprotein (LDL) cholesterol remains the primary target while apolipoprotein B (apoB) and non–high-density lipoprotein (non-HDL) cholesterol are secondary targets.ObjectivesThis study sought to determine if elevated apoB and/or non-HDL cholesterol are superior to elevated LDL cholesterol in identifying statin-treated patients at residual risk of all-cause mortality and myocardial infarction.MethodsIn total, 13,015 statin-treated patients from the Copenhagen General Population Study were included with 8 years median follow-up. Cox regressions among apoB, non-HDL cholesterol, and LDL cholesterol, respectively, and all-cause mortality or myocardial infarction were examined on continuous scales by restricted cubic splines and by categories of concordant and discordant values defined by medians.ResultsHigh apoB and non-HDL cholesterol were associated with increased risk of all-cause mortality and myocardial infarction, whereas no such associations were found for high LDL cholesterol. Compared with concordant values below medians, discordant apoB above the median with LDL cholesterol below yielded hazard ratios of 1.21 (95% confidence interval [CI]: 1.07 to 1.36) for all-cause mortality and 1.49 (95% CI: 1.15 to 1.92) for myocardial infarction. Corresponding values for high non-HDL cholesterol with low LDL cholesterol were 1.18 (95% CI: 1.02 to 1.36) and 1.78 (95% CI: 1.35 to 2.34). In contrast, discordant high LDL cholesterol with low apoB or non-HDL cholesterol was not associated with increased risk of all-cause mortality or myocardial infarction. Also, discordant high apoB with low non-HDL cholesterol yielded hazard ratios of 1.21 (95% CI: 1.03 to 1.41) for all-cause mortality and of 0.93 (95% CI: 0.62 to 1.40) for myocardial infarction. Furthermore, dual discordant apoB and non-HDL cholesterol above the medians with LDL cholesterol below presented hazard ratios of 1.23 (95% CI: 1.07 to 1.43) for all-cause mortality and 1.82 (95% CI: 1.37 to 2.42) for myocardial infarction.ConclusionsIn statin-treated patients, elevated apoB and non-HDL cholesterol, but not LDL cholesterol, are associated with residual risk of all-cause mortality and myocardial infarction. Discordance analysis demonstrates that apoB is a more accurate marker of all-cause mortality risk in statin-treated patients than LDL cholesterol or non-HDL cholesterol, and apoB in addition is a more accurate marker of risk of myocardial infarction than LDL cholesterol.     

Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease

OBJECTIVE: To evaluate and synthesize the evidence on the effect of supplements of vitamin E on the prevention and treatment of cardiovascular disease. DESIGN: Systematic review of placebo-controlled randomized controlled trials; meta-analysis where justified. MEASUREMENTS AND MAIN RESULTS: Eighty-four eligible trials were identified. For the outcomes of all-cause mortality, cardiovascular mortality, fatal or nonfatal myocardial infarction, and blood lipids, neither supplements of vitamin E alone nor vitamin E given with other agents yielded a statistically significant beneficial or adverse pooled relative risk (for example, pooled relative risk of vitamin E alone = 0.96 [95% confidence interval (CI), 0.84 to 1.10]; 0.97 [95% CI, 0.80 to 1.90]; and 0.72 [95% CI, 0.51 to 1.02] for all-cause mortality, cardiovascular mortality, and nonfatal myocardial infarction, respectively. CONCLUSIONS: There is good evidence that vitamin E supplementation does not beneficially or adversely affect cardiovascular outcomes.     

Ventricular arrhythmias and risk of death and acute myocardial infarction in apparently healthy subjects of age >or=55 years

Increased ventricular ectopic activity and even more complex arrhythmias are not uncommon in subjects without apparent heart disease. However, their prognostic significance has been controversial and not updated in recent years. The prevalence and prognostic significance of different ventricular arrhythmias were studied in a cohort of middle-aged and elderly subjects without apparent heart disease. Six hundred seventy-eight men and women aged 55 to 75 years without a history of heart disease or stroke were included. Baseline examinations included physical examinations, fasting laboratory testing, and 48-hour ambulatory electrocardiographic monitoring. All patients were followed for up to 5 years. Combined events were defined as all-cause mortality or acute myocardial infarction. A cardiovascular event was defined as cardiovascular death or acute myocardial infarction. In total, 84% had 0 to 10 ventricular premature complexes (VPCs)/hour, 8% had 11 to 30 VPCs/hour, and 8% had >30 VPCs/hour; 10.8% had >or=1 run of >or=3 VPCs. Frequent VPCs (>or=30/hour) was a significant predictor of combined (hazard ratio 2.47, 95% confidence interval 1.29 to 4.68, p = 0.006) and cardiovascular (hazard ratio 2.85, 95% confidence interval 1.16 to 7.0, p = 0.023) event rates, after adjustment for conventional risk factors. Runs of >or=4 VPCs/day or >or=2 doublets/day were also associated with a poor prognosis, but only in the presence of frequent VPCs. The detection of a single VPC on standard electrocardiography was a significant predictor of frequent VPCs and an independent predictor of events (hazard ratio 2.6, 95% confidence interval 1.02 to 6.66, p = 0.045). In conclusion, apparently healthy, middle-aged and elderly subjects with frequent VPCs (>or=30/hour) have a poor prognosis. According to current guidelines, strict risk-factor modification and primary prevention are justified in these high-risk subjects.     

Association of Depression and Cardiovascular Disease

BackgroundCardiovascular disease remains the leading worldwide cause of mortality. There has been increased awareness of the impact of psychological health on cardiovascular disease. In particular, major depression has been linked to increased all-cause mortality, development of cardiovascular disease, and worse outcomes in those with existing cardiovascular disease.MethodsWe conducted a meta-analysis assessing the incidence of cardiovascular disease and cardiovascular disease outcomes among those with major depressive disorder.ResultsAmong 26 studies of 1,957,621 individuals, depression was associated with increased risk of incident stroke (hazard ratio [HR] 1.13; 95% confidence interval [CI], 1.00-1.28), myocardial infarction (HR 1.28; 95% CI, 1.14-1.45), congestive heart failure (HR 1.04; 95% CI, 1.00-1.09), or any cardiovascular disease (HR 1.16; 95% CI, 1.04-1.30). Depression was associated with increased risk of all-cause mortality (HR 1.43; 95% CI, 1.27-1.60), cardiovascular disease mortality (HR 1.44; 95% CI, 1.27-1.63), and congestive heart failure mortality (HR 3.20; 95% CI, 1.29-7.94).ConclusionDepression has a significant negative impact on development of cardiovascular disease and on cardiovascular disease outcomes. Further efforts to understand and mitigate these impacts are prudent.     

The value of C-reactive protein in cardiovascular risk prediction: the Rotterdam Study

BACKGROUND: Epidemiologic studies have shown that C-reactive protein (CRP) is a risk factor for coronary heart disease. Whether routine measurement of CRP has a role in the prediction of future coronary disease in everyday clinical practice has not yet been investigated. METHODS: Within the Rotterdam Study, a population-based cohort study of 7983 men and women 55 years and older, we conducted a nested case-control study to investigate the value of CRP in coronary disease prediction. Data are based on 157 participants who experienced a myocardial infarction during follow-up and 500 randomly selected controls. High-sensitivity CRP and traditional cardiovascular risk factors were measured at baseline. RESULTS: The age- and sex-adjusted relative risk of myocardial infarction for subjects in the highest quartile of the population distribution of CRP compared with the lowest quartile was 2.0 (95% confidence interval, 1.1-3.4). After additional adjustment for traditional cardiovascular risk factors, the increase in risk largely disappeared (odds ratio, 1.2; 95% confidence interval, 0.6-2.2). Adding CRP to a coronary disease risk function based on risk factors that are routinely assessed in clinical practice or to the Framingham risk function did not improve the area under the receiver operating characteristic curve of these risk functions. Sensitivity and specificity of both risk functions, computed after dichotomizing the estimated disease probabilities using prespecified cutoff points, hardly improved when CRP was added. CONCLUSION: Measurement of CRP in elderly people has no additional value in coronary disease risk prediction when traditional cardiovascular risk factors are known.     

O Prognóstico da Doença Arterial Coronariana em um Hospital Público no Brasil: Achado do Estudo ERICO

BackgroundLong-term prognosis post-acute coronary syndrome (ACS) in secondary care is not well-known. The severity of coronary artery disease (CAD) as a predictor of long-term mortality was evaluated in a community hospital in Brazil.ObjectiveWe aimed to compare short and long-term prognosis after an ACS event according to severity of obstructive disease in patients attended in a secondary community hospital from prospective CAD cohort in Brazil (the Strategy of Registry of Acute Coronary Syndrome, ERICO study).MethodsSurvival analyses were performed by Kaplan-Meier curves and Cox proportional hazard models (hazard ratios (HR) with respective 95% confidence interval (CI) to evaluate cumulative all-cause, CVD and CAD mortality according the coronary artery obstruction: no-obstruction (reference group), 1-vessel-disease, 2-vessel-disease, multivessel-disease) among 800 adults from an ERICO study during a 4-year-follow-up. HR are presented as crude and further adjusted for potential confounders from 180 days to 4-year follow-up after ACS. A p-value <0.05 was considered statistically significant.ResultsPoorer survival rates were detected among individuals with multivessel-disease (all-cause, CVD and CAD, p-log rank< 0.0001). After multivariate adjustments, multivessel-disease |(HR; 2.33 (CI 95%; 1.10-4.95)) and 1-vessel-disease obstructed (HR; 2.44 (CI 95%; 1.11-5.34)) had the highest risk for all-cause mortality compared to those with no obstruction at 4-year follow-up.ConclusionsNot only multivessel-disease, but also 1-vessel-disease patients showed a high long-term mortality risk post-ACS. These findings highlight the importance of having a better approach in the treatment and control of cardiovascular risk even in apparently low-risk individuals attended to in secondary care.