Homocysteine is an independent predictor of long-term cardiac mortality in patients with stable coronary artery disease in the era of statins.

BACKGROUND: Homocysteine (Hcy) is considered a risk factor for cardiovascular disease. OBJECTIVE: To explore the long-term prognostic value of Hcy in patients with stable coronary artery disease (CAD) in the era of statins. METHODS: A total of 876 consecutive patients with stable CAD were recruited and followed up for a median of 6.1 years. Lipids and Hcy levels were measured at baseline. Primary endpoints were cardiac death and secondary endpoints were hospitalizations for acute coronary syndrome, myocardial revascularization, arrhythmic event or ischemic stroke. RESULTS: Follow-up data were obtained from 842 patients of whom 70 had a cardiac death (8.3%), while 258 (30.6%) met the secondary endpoints. Seven hundred four patients (83.6%) were on statins. In univariate Cox regression analysis Hcy predicted the occurrence of cardiac death [hazard ratio: 1.030; 95% confidence interval (CI): 1.018-1.042, P < 0.001] but not the occurrence of secondary endpoints (hazard ratio: 1.010; 95% CI: 0.999-1.020, P = 0.081). Hcy remained an independent predictor of cardiac death after adjustment for conventional risk factors, ejection fraction and statin use (hazard ratio: 1.030; 95% CI: 1.017-1.044, P < 0.001). Patients in the highest tertile of Hcy levels (>14.1 µmol/L) had three times higher risk of cardiac death compared with patients in the lowest tertile (<10.3 µmol/L) (hazard ratio = 3.036, CI: 1.983-4.649, P < 0.001). CONCLUSION: Hcy is an independent predictor of cardiac death in patients with stable CAD in the era of statins.

High levels of lipoprotein (a) and premature acute coronary syndrome.

BACKGROUND AND AIMS: High levels of lipoprotein(a) [Lp(a)] are associated with increased risk of acute coronary syndrome (ACS). We explored whether Lp(a) exhibits a stronger association with premature ACS. METHODS: A case-control study was conducted; 1457 patients with a history of ACS (54.8 ± 13 years, 86% males) and 2090 age-sex matched adults free of cardiovascular disease were enrolled. Bio-clinical characteristics [risk factors, low-density lipoprotein-cholesterol, Lp(a)] were derived through standard procedures. RESULTS: A 10 mg/dL increase in Lp(a) was associated with 4% (95% CI, 1.01 to 1.02) higher likelihood of having ACS in younger (<45 years) and 2% (95% CI, 1.01 to 1.02) higher likelihood in middle-aged (45-60 years) individuals. Adjusting for common risk factors, elevated Lp(a), i.e. >50 mg/dL, was still associated with increased likelihood of ACS in younger adults (<45 years) (OR = 2.88, 95% CI, 1.7 to 4.6) and in middle aged ones (45 and 60 years) (OR = 2.06, 95% CI, 1.4 to 3.2), but not in older participants (>60 years) (OR = 1.31, 95% CI, 0.8 to 2.4). CONCLUSIONS: Lp(a) seems to be an independent risk factor for ACS in individuals <45 years, and high Lp(a) levels increase by ∼3folds the risk for ACS. The association is preserved but is less in middle-aged individuals (45-60 years) and is abolished >60 years.

Short-term effects of Mediterranean-type diet intervention on soluble cellular adhesion molecules in subjects with abdominal obesity.

BACKGROUND & AIMS: Abdominal obesity (AO) is associated with increased risk for cardiovascular disease and with increased production of adhesion molecules. The present work examined the effect of a Mediterranean-style diet on soluble cellular adhesion molecules in individuals with AO. METHODS: Ninety subjects with AO without cardiovascular disease or diabetes mellitus were randomly allocated to the intervention or control group and were instructed to follow a Mediterranean-style diet for two months. Intervention group followed a specific relevant food plan with close dietetic supervision and provision of basic foods. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), sP and sE-selectin, C-reactive protein (CRP) and interleukin-6 (IL-6) were measured. RESULTS: Subjects in the intervention group increased their intake of total fat, monounsaturated fatty acids, dietary fiber, vitamin C, and alcohol compared to controls, while decreased their intake of saturated fat. Although there was a significant decrease in CRP, sP-selectin and in sE-selectin in the intervention group, and an increase in sVCAM-1 in the control group, between-group analysis showed no statistically significant differences. There were also no significant changes in sICAM-1, and IL-6 levels after intervention. CONCLUSIONS: Mediterranean-type diet for two months combined with close dietetic supervision showed a beneficial tendency towards the down-regulation of some markers of vascular inflammation, although the comparison between groups after the intervention did not reach statistical significance. A longer period of dietary intervention may be required to further support these changes.

The impact of smoking on long-term outcome of patients with premature (≤35years) ST-segment elevation acute myocardial infarction.

BACKGROUND: There are few data regarding the long-term prognosis of young survivors of acute myocardial infarction (AMI). We explored the long-term outcome in individuals who had sustained a premature ST-segment elevation AMI. METHODS: We recruited 257 consecutive patients who had survived their first AMI ≤35years of age. Patients were followed up for up to 18years. Clinical end points included all major adverse coronary events (MACE): cardiac death, readmission for acute coronary syndrome, arrhythmias, or coronary revascularization due to clinical deterioration. RESULTS: The most prevalent risk factor at presentation was smoking (93.7%). Follow-up data were obtained from 237 patients (32.2±3.7years old). The median follow-up period was 9.1years. During follow-up, 139 (58.6%) patients reported continuation of smoking. Ninety-one (38.4%) patients had recurrent MACE (13 deaths, 59 acute coronary syndromes, 2 arrhythmias, and 17 revascularizations). Multivariable Cox regression analysis showed that persistence of smoking, left ventricular ejection fraction (LVEF), and reperfusion therapy (fibrinolysis or primary coronary angioplasty) were independent predictors of MACE after adjustment for conventional risk factors. Continuation of smoking remained an independent predictor for MACE after additional adjustments for LVEF (hazard ratio 2.154, 95% CI 1.313-3.535, P=.002) or reperfusion treatment (hazard ratio 2.327, 95% CI 1.423-3.804, P=.001). Harrell c statistic showed that the model with persistent smoking had the best discriminatory power compared with models with LVEF or reperfusion treatment. CONCLUSIONS: In the era of statins and reperfusion treatment, continuation of smoking is the strongest independent long-term predictor for recurrent MACE in young survivors of premature AMI.

Visceral adipose tissue is a better predictor of subclinical carotid atherosclerosis compared with waist circumference.

We investigated whether visceral adipose tissue (VAT) measured by ultrasonography is better than waist circumference (WC) in predicting the presence of subclinical carotid atherosclerosis. We recruited 100 individuals without a history of cardiovascular disease or diabetes mellitus. VAT volume was measured by ultrasonography and common carotid artery intima-media thickness (CCA-IMT) by B-mode ultrasonography. Both VAT and WC were positively associated with body mass index, triglycerides, uric acid, systolic/diastolic blood pressure and high sensitivity C-reactive protein and inversely correlated with high-density lipoprotein cholesterol. However, only VAT was associated with CCA-IMT (r = 0.309, p = 0.002). Multivariate logistic regression analysis revealed that VAT, but not WC, was an independent predictor of carotid plaques after adjustment for cardiovascular risk factors (odds ratio [OR] = 1.017, 95% confidence interval [CI] = 1.003-1.031, p = 0.017), and this association persisted after additional adjustment for WC (OR = 1.024, 95% CI = 1.003-1.031, p = 0.027). Our data suggest that VAT volume measured by ultrasonography may be a better predictor of subclinical carotid atherosclerosis than waist circumference in healthy individuals.

Lipoprotein-associated phospholipase A(2) bound on high-density lipoprotein is associated with lower risk for cardiac death in stable coronary artery disease patients: a 3-year follow-up.

OBJECTIVES: The aim of this study was to examine the prognostic value of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) associated with high-density lipoprotein (HDL) (HDL-Lp-PLA(2)) in patients with stable coronary artery disease (CAD). BACKGROUND: Lp-PLA(2) is a novel risk factor for cardiovascular disease. It has been postulated that the role of Lp-PLA(2) in atherosclerosis may depend on the type of lipoprotein with which it is associated. METHODS: Total plasma Lp-PLA(2) and HDL-Lp-PLA(2) mass and activity, lipids, and C-reactive protein were measured in 524 consecutive patients with stable CAD who were followed for a median of 34 months. The primary endpoint was cardiac death, and the secondary endpoint was hospitalization for acute coronary syndromes, myocardial revascularization, arrhythmic event, or stroke. RESULTS: Follow-up data were obtained from 477 patients. One hundred twenty-three patients (25.8%) presented with cardiovascular events (24 cardiac deaths, 47 acute coronary syndromes, 28 revascularizations, 22 arrhythmic events, and 2 strokes). Total plasma Lp-PLA(2) mass and activity were predictors of cardiac death (hazard ratio [HR]: 1.013; 95% confidence interval [CI]: 1.005 to 1.021; p = 0.002; and HR: 1.040; 95% CI: 1.005 to 1.076; p = 0.025, respectively) after adjustment for traditional risk factors for CAD. In contrast, HDL-Lp-PLA(2) mass and activity were associated with lower risk for cardiac death (HR: 0.972; 95% CI: 0.952 to 0.993; p = 0.010; and HR: 0.689; 95% CI: 0.496 to 0.957; p = 0.026, respectively) after adjustment for traditional risk factors for CAD. CONCLUSIONS: Total plasma Lp-PLA(2) is a predictor of cardiac death, while HDL-Lp-PLA(2) is associated with lower risk for cardiac death in patients with stable CAD, independently of other traditional cardiovascular risk factors.

Attainment of optional low-density lipoprotein cholesterol goal of less than 70 mg/dl and impact on prognosis of very high risk stable coronary patients: a 3-year follow-up.

OBJECTIVES: We aimed to investigate the proportion of very high-risk patients with coronary heart disease (CHD) who achieve the optional low-density lipoprotein cholesterol (LDL-C) target of <70 mg/dl (1.8 mmol/liter), the factors that influence the success rate and the impact on their prognosis. RESEARCH DESIGN AND METHODS: We enrolled 1337 consecutive patients with stable CHD. Fasting lipids were determined and all cardiovascular events were recorded during a median follow-up of 33 months. RESULTS: The majority (86.5%) of patients were taking lipid-lowering medication (95.5% statins), but only 50.6% had LDL-C levels of <100 mg/dl (2.6 mmol/liter). In total, 941 (70.4%) patients were considered very high risk and only 15.1% of them had LDL-C levels of <70 mg/dl. Τhe use of intensive lipid-lowering medication was associated with 12-fold (95% CI 6.98-20.76; p<0.001) higher possibility in achieving LDL-C levels of < 70 mg/dl. Attainment of LDL-C levels of < 70 mg/dl by patients at very high risk were independent predictors of all cardiovascular events (HR=0.34, 95% CI 0.17-0.70; p=0.003). CONCLUSIONS: The vast majority of very high-risk patients do not achieve the optional LDL-C goal; this is mainly due to the suboptimal uptitration of statin dose and is translated into loss of clinical benefits.

Elevated soluble intercellular adhesion molecule-1 levels are associated with poor short-term prognosis in middle-aged patients with acute ischaemic stroke.

BACKGROUND: There is increasing evidence that cellular adhesion molecules (CAMs) play an important role in the pathophysiology of acute ischaemic stroke. We examined the prognostic value of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) on in-hospital mortality in patients with ischaemic stroke. METHODS: We recruited 241 consecutive patients 322 ng/ml were the optimal points that discriminated those who died from the rest of the patients. CONCLUSIONS: High sICAM-1 levels on admission are associated with early death in ischaemic middle-aged stroke patients suggesting a pathogenetic role of inflammation in the evolution of ischaemic stroke.

Simvastatin exerts its anti-inflammatory effect in hypercholesterolaemic patients by decreasing the serum levels of monocyte chemoattractant protein-1.

AIM: To assess the effect of simvastatin on serum levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-6, tumor necrosis factor-alpha, macrophage colony stimulating factor, C-reactive protein and serum amyloid A in hypercholesterolaemic patients without coronary heart disease. METHODS: Sixty consecutive hypercholesterolaemic patients were randomly assigned in a 2:1 process to 40 mg of simvastatin daily (n=40) and to hypolipidaemic only diet (n=20) for 3 months. Blood was taken at baseline and at the end of the study and analysed for lipids and inflammatory markers. RESULTS: From the inflammatory markers only MCP-1 was decreased significantly (217.4+/-48 versus 177+/-75 pg/ml, p<0.001) after treatment with simvastatin and this reduction was independent of lipid changes. CONCLUSION: Simvastatin significantly decreases only MCP-1 levels in hypercholesterolaemic patients suggesting that this molecule is probably a sensitive marker to detect the anti-inflammatory effect of simvastatin in blood.

Inflammatory markers and in-hospital mortality in acute ischaemic stroke.

BACKGROUND: There is substantial evidence that cerebral ischaemia triggers an inflammatory response. We examined the short-term prognostic value on mortality of C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) in patients with ischaemic stroke. METHODS: We recruited 203 consecutive patients, under the age of 66 years (mean age=54.2+/-8.1 years, men=132) who admitted to the Neurology Department with the diagnosis of non-haemorrhagic stroke. Patients in atrial fibrillation or with evidence of inflammatory or malignant disease were excluded. The diagnosis was confirmed with a computed tomography or magnetic resonance imaging of the brain within 24h of admission. CRP, IL-6 and SAA levels were determined within 12h from admission. RESULTS: Fourteen (6.9%) patients died during hospitalization. Serum concentrations of CRP, IL-6 and SAA were significantly higher in patients who died compared with those who survived and were independently associated with early death, after adjusting for various confounding factors. For one unit increase in IL-6, CRP and SAA there was an 18%, 14% and 9% higher risk of dying during hospitalization, respectively. Comparisons of the areas under the ROC curve showed that IL-6 had the best predictive ability. Age-adjusted cut-off point analysis showed that IL-6 levels >13 pg/ml were the optimal point that discriminated those who died from the rest of the patients (sensitivity=85% and specificity=93%). CONCLUSIONS: We demonstrated that in-hospital mortality in ischaemic stroke is associated with an exacerbation of inflammatory response as it is reflected by the higher serum levels of IL-6, CRP and SAA. From the inflammatory markers high IL-6 levels had the strongest independent predictive value for in-hospital mortality.

Usefulness of elevated levels of soluble vascular cell adhesion molecule-1 in predicting in-hospital prognosis in patients with unstable angina pectoris.

To assess the in-hospital prognostic value of cellular adhesion molecules (CAMs), the levels of soluble CAMs were measured at admission in 114 patients with severe unstable angina. Patients with an eventful in-hospital course (death, nonfatal acute myocardial infarction, and recurrence of angina) had higher levels of soluble vascular cell adhesion molecule-1 than those without events (p = 0.01); this association was independent of classic risk factors and C-reactive protein.

Prognostic value of C-reactive protein, fibrinogen, interleukin-6, and macrophage colony stimulating factor in severe unstable angina.

BACKGROUND: Inflammatory process plays an important role in the pathogenesis of acute coronary syndromes. HYPOTHESIS: The study was undertaken to evaluate whether admission levels of C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6). and macrophage colony stimulating factor (MCSF) can predict short-term prognosis in patients with unstable angina. METHODS: C-reactive protein, fibrinogen, IL-6, and MCSF were measured on admission in 141 consecutive patients, aged 59 +/- 10 years, with unstable angina (Braunwald class IIIb). Patients were divided into two groups according to their in-hospital outcome: Group 1 comprised 77 patients with a complicated course (2 died, 15 developed nonfatal myocardial infarction, and 60 had recurrence of angina), and Group 2 comprised 64 patients with an uneventful course. RESULTS: Admission median levels of CRP (8.8 vs. 3.1 mg/l, p = 0.0002). fibrinogen (392 vs. 340 mg/dl, p = 0.008), IL-6 (8.8 vs. 4.5 pg/ml, p = 0.03), and MCSF (434 vs. 307 pg/ml, p = 0.0001) were higher in Group I than in Group 2. The MCSF levels were an independent risk factor for in-hospital events, with an adjusted odds ratio for eventful in-hospital outcome of 3.3 (95% confidence interval 1-10.9, p = 0.04), and correlated with levels of IL-6 (r(s) = 0.52, p = 0.0001), CRP (r(s) = 0.43, p = 0.0001), and fibrinogen (r(s) = 0.25, p = 0.004). CONCLUSIONS: These findings suggest that among the studied inflammatory indices only increased admission levels of MCSF are strongly and independently related with adverse short-term prognosis in patients with severe unstable angina.