Atorvastatin treatment improves endothelial function through endothelial progenitor cells mobilization in ischemic heart failure patients.

OBJECTIVE: Endothelial function is an independent predictor of prognosis in heart failure (HF) subjects. Statins, beyond their lipid lowering role, exert beneficial effect in patients with atherosclerosis. In the present study we examined the impact of low and intermediate dose atorvastatin treatment on endothelial function, bone marrow-derived endothelial progenitor cells (EPC) mobilization and inflammatory status according to HF patient status. METHODS: We studied the effect of 4 weeks administration of atorvastatin in 26 patients with ischemic HF. The study was carried out on two separate arms, one with atorvastatin 40 mg/d and one with atorvastatin 10 mg/d (randomized, double-blind, cross-over design). The number of circulating CD34(+)/CD133(+)/KDR(+) EPCs was evaluated by flow cytometry. Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery. Serum levels of tumor necrosis factor alpha (TNF-α) were measured by ELISA. RESULTS: Treatment with atorvastatin 40 mg/d significantly increased circulating EPC (p = 0.002), FMD (p = 0.001) and reduced TNF-α (p = 0.01) compared to baseline. Similarly, treatment with atorvastatin 10 mg/day increased circulating EPC (p = 0.01), FMD (p = 0.08) and reduced TNF-α (p = 0.01) compared to baseline. Interestingly, with 40 mg/day atorvastatin treatment the increase in EPC was higher in subjects categorized as NYHA class II compared to subjects categorized as NYHA class III (p = 0.03). CONCLUSIONS: Our results confirmed the distinct impact of atorvastatin treatment on the restoration of endothelial function due to EPC mobilization in ischemic HF subjects. Moreover, these findings provide the potential clinical significance of EPC status monitoring to individualize treatment in HF subjects.

Dose-dependent effects of short term atorvastatin treatment on arterial wall properties and on indices of left ventricular remodeling in ischemic heart failure.

OBJECTIVES: Statins, beyond their lipid lowering role, exert beneficial effect on endothelial function in patients with atherosclerosis. Aim of the present study was to examine the short term pleiotropic effects of different doses of atorvastatin treatment, on endothelial function, arterial stiffness and indices of left ventricular remodeling in heart failure (HF) patients. METHODS: We studied the effect of 4 weeks administration of atorvastatin in 22 patients with ischemic HF. The study was carried out on two separate arms, one with atorvastatin 40 mg/d and one with atorvastatin 10 mg/d (randomized, double-blind, cross-over design). Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery and arterial stiffness by augmentation index (AIx). Serum levels of matrix metalloproteinase-9 (MMP-9) and intracellular adhesion molecule-1 (sICAM-1) were measured as biomarkers of left ventricular remodeling and endothelial function, respectively, while, b-type natriuretic peptide (BNP) was measured as a marker of left ventricular function. RESULTS: Compared to baseline, atorvastatin 40 mg/d significantly improved FMD values (3.18 ± 3.03% vs. 5.98 ± 2.49%, p = 0.001) and AIx values (25.98 ± 8.55% vs. 23.09 ± 8.87%, p = 0.046). In addition, compared to baseline measurements, treatment with atorvastatin 40 mg/d resulted in significantly decreased levels of serum logMMP-9 levels (2.47 ± 0.23 ng/ml vs. 2.39 ± 0.24 ng/ml, p = 0.04) and of logICAM-1 levels (2.46 ± 0.13 ng/ml vs. 2.37 ± 0.16 ng/ml, p < 0.001). No significant changes were found after treatment with atorvastatin 10 mg/d in the aforementioned parameters. CONCLUSIONS: Short term treatment with 40 mg/d of atorvastatin exerts beneficial impact on arterial wall properties and on indices of left ventricle remodeling in heart failure patients.

Hierarchical analysis of cardiovascular risk factors in relation to the development of acute coronary syndromes, in different parts of Greece: the CARDIO2000 study.

During 2000 to 2002, 700 men (59 +/- 10 years) and 148 women (65 +/- 9 years) patients with first event of an ACS were randomly selected from cardiology clinics of Greek regions. Afterwards, 1078 population-based, age-matched and sex-matched controls were randomly selected from the same hospitals. The frequency ratio between men and women in the case series of patients was about 4:1, in both south and north Greek areas. Hierarchical classification analysis showed that for north Greek areas family history of coronary heart disease, hypercholesterolemia, hypertension, diabetes (explained variability 35%), and less significantly, dietary habits, smoking, body mass index, and physical activity status (explained variability 4%) were associated with the development of ACS, whereas for south Greek areas hypercholesterolemia, family history of coronary heart disease, diabetes, smoking, hypertension, dietary habits, physical activity (explained variability 34%), and less significantly body mass index (explained variability <1%), were associated with the development of the disease.

Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major.

BACKGROUND: Beta-thalassemia major is associated with increased cardiovascular risk, although the underlying mechanisms remain unclear. We examined endothelial function and serum levels of inflammatory mediators in transfusion-dependent patients with beta-thalassemia major. METHODS: The study population consisted of 67 patients with homozygous beta-thalassemia major, (aged 24.6+/-0.7 years) and 71 healthy age and sex matched controls. Forearm blood flow was measured with gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was expressed as the percentage change of forearm blood flow from baseline to the maximum flow during reactive hyperemia or sublingual nitroglycerin, respectively. Serum levels of interleukin 6 (IL-6), soluble vascular cell adhesion molecule (sVCAM-1) and soluble intercellular adhesion molecule (sICAM-1) were determined with ELISA. RESULTS: Patients had significantly lower levels of total cholesterol (125+/-4.5 vs. 207+/-7 mg/ml, p<0.01), ApoA1 (120+/-3 vs. 129+/-5 mg/ml, p<0.05), ApoB (60.5+/-2 vs. 95+/-4 mg/ml, p<0.01), ApoE (3+/-2 vs. 4+/-0.2 mg/ml, p<0.01) and Lp(a) (7.9+/-1.3 vs. 14.5+/-3.2 mg/ml, p<0.01) than controls. IL-6 levels were significantly higher in patients (3.03+/-0.31 pg/ml) than controls (1.15+/-0.15 pg/ml, p<0.01). Similarly, sVCAM-1 and sICAM-1 levels were significantly higher in patients (513+/-31 and 368+/-25.5 ng/ml, respectively) than controls (333+/-13.8 and 272+/-14.05 ng/ml, respectively, p<0.01 for both). Maximum hyperemic forearm blood flow and RH% were lower in patients (7.1+/-0.3 ml/100 ml tissue/min and 49+/-2.8%, respectively) than controls (8.26+/-0.32 ml/100 ml tissue/min and 86.3+/-5.57%, respectively, p<0.01 for both). CONCLUSIONS: Beta-thalassemia major is associated with impaired endothelial function and increased levels of IL-6, sVCAM-1 and sICAM-1, suggesting a potential role of inflammation and endothelial dysfunction in the complications of the disease.

Geographical influences on the association between adherence to the Mediterranean diet and the prevalence of acute coronary syndromes, in Greece: the CARDIO2000 study.

OBJECTIVE: We evaluated the interaction between adherence to the Mediterranean diet and region of Greece on the likelihood of having acute coronary syndromes (ACS). METHODS: During 2000-2001, a random sample of 848 patients (61+/-10 years) with their first coronary heart disease event, and 1078 frequency matched (by age-sex) controls with no cardiovascular disease in their medical history, from all the country, entered into the study. Among several factors, adherence to the Mediterranean diet was assessed by a diet-score that incorporated the inherent characteristics of this diet. RESULTS: The multi-adjusted analysis showed that a 10-unit increase in the diet score was associated with a 27% (95% CI 0.66 to 0.89) decrease of the odds of having ACS. Moreover, a highly significant interaction was observed between region and diet score (p<0.001). The odds ratios varied from roughly 0.5 in Southern to 1.2 or more in Northern Greek regions (p for heterogeneity<0.05). Differences in food patterns consumed did not explain the previous findings. In addition, when we stratified our analysis by rural and urban areas we found significant differences in the estimated odds ratios (p for interaction between diet score and area=0.01), since a 10-unit increase in the diet score was associated with 22% (95% CI 0.63 to 0.96) lower odds n urban areas and 31% (95% CI 0.48 to 0.98) lower odds in rural areas. CONCLUSION: Our findings underline the significance of the Mediterranean diet on the primary prevention of ACS. Moreover, we revealed a geographical variation in the importance of this dietary pattern on coronary risk, independent from the composition of food patterns followed and the prevalence of the common cardiovascular risk factors.

Evidence for association between endothelial nitric oxide synthase gene polymorphism (G894T) and inflammatory markers: the ATTICA study.

BACKGROUND: We evaluated the effect of the point mutation of guanine to thymine at nucleotide position 894 (G894T) of the endothelial nitric oxide synthase (eNOS) gene on inflammatory and oxidative stress markers. METHODS: We studied genetic information from 270 men (18-87 years old) and 325 women (18-89 years old). Participants without any clinical evidence of cardiovascular or other atherosclerotic disease were randomly selected from the general population according to the age-sex distribution of Athens greater area. Genomic DNA was extracted from 2 to 5 mL of fresh or frozen whole blood using standard methods. RESULTS: The DNA analysis showed that 10.6% of the participants were Asp-homozygotes (Asp/Asp), 40% heterozygotes (Asp/Glu) and 49.4% Glu-homozygotes (Glu/Glu). Compared to Asp/Glu and Glu/Glu, Asp/Asp had higher levels of fibrinogen (332 +/- 46 or 329 +/- 33 vs 319 +/- 29 mg/dL, P =.029), white blood cells (6.9 +/- 0.6 or 6.5 +/- 0.3 vs 6.1 +/- 0.9 x 10(3) counts, P =.044), and oxidized low-density lipoprotein cholesterol (68 +/- 21 or 61 +/- 22 vs 59 +/- 20 mg/dL, P =.039), after controlling for several potential confounders. An insignificant association was found between homocysteine (P =.08), C-reactive protein (P =.096), and the distribution of G894T polymorphism (P <.1). No association between the distribution of the polymorphism and hypertension status of the participants was observed. CONCLUSIONS: Our results imply that G894T polymorphism of the endothelial nitric oxide synthase gene is associated with elevated levels of inflammatory and oxidative stress markers, which may partially explain the increased prevalence of G894T polymorphism among patients with cardiovascular disease.

Increased plasma homocysteine concentrations in healthy people with hostile behavior: the ATTICA study.

BACKGROUND: One of the psychological factors showing significant association with the development of coronary heart disease is hostility. However, the pathway by which hostility may affect coronary risk is not fully understood. Thus we evaluated the association between hostility and inflammation (thrombotic marker) in a population-based sample of males and females with no clinical evidence of cardiovascular disease. MATERIAL/METHODS: The ATTICA study is a health and nutrition survey carried out in the province of Attica, Greece, during 2001-2002. 410 participants (200 men 39+/-12 years old, and 210 women 35+/-10 years old) completed the Hostility and Direction of Hostility questionnaire (range 0-55) and had blood taken for the assessment of high sensitivity C--reactive protein, fibrinogen, white blood cell counts, and plasma homocysteine concentrations. RESULTS: 111 (27%) of the participants were classified in the upper quartile of the hostility scale (>21 score) and 119 (29%) were classified in the lower quartile (<11 score). Multivariate linear regression analysis revealed that hostility score associated positively only with homocysteine levels (standardized Beta=0.124, adj. R2=6%, p=0.015), after controlling for age, gender, educational status, body mass index, physical activity levels, and dietary habits of the participants. In particular, a 10-unit increase in the hostility scale was associated with a 2.9 micromol/l rise in homocysteine levels. CONCLUSIONS: Our findings suggest a positive relationship between homocysteine and hostility; however, whether hostility influences inflammation or the thrombotic process remains to be evaluated by future prospective studies.

Can a Mediterranean diet moderate the development and clinical progression of coronary heart disease? A systematic review.

BACKGROUND: It has been suggested that adherence to a Mediterranean diet reduces all causes of mortality, especially death rates due to coronary heart disease. In this review we summarize the findings of observational studies that evaluated the effect of the Mediterranean dietary pattern in the primary and secondary prevention of coronary heart disease. MATERIAL/METHODS: We retrieved published results from prospective and case-control studies which evaluated the association between adherence to a Mediterranean diet and the occurrence of coronary heart disease outcomes. RESULTS: The benefits from the Mediterranean diet were significant in all studies. The reduction in the risk of coronary heart disease varied from 8% to 45%, depending on the increment used by the investigators in the presentation of their results. CONCLUSIONS: The systematically reviewed studies reveal a cardio-protective effect of the Mediterranean diet and point to this dietary pattern as highly appropriate for public health objectives.

Impact of lifestyle habits on the prevalence of the metabolic syndrome among Greek adults from the ATTICA study.

BACKGROUND: Individuals with the metabolic syndrome (MS) are at high risk for coronary heart disease and may benefit from aggressive lifestyle modification. In this study, we evaluated the effect of leisure time physical activity (PA) and the Mediterranean diet (MD) on the prevalence of the MS. METHODS: The ATTICA study is a health and nutritional survey. On the basis of a multistage, random sampling, 1128 men and 1154 women (>18 years old) without any evidence of cardiovascular disease or diabetes mellitus were enrolled from the greater Athens area during 2001 to 2002. The MS was defined according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria. PA was determined from a detailed questionnaire and graded according to the kcal/min expanded. MD was assessed through a validated nutrient questionnaire. RESULTS: The overall prevalence of the MS was 453 of 2282 subjects (19.8%). Of these subjects, 284 (25.2%) were men and 169 (14.6%) were women (P <.001). The prevalence of the MS increased accordingly to age (P for trend <.001). With multiple logistic regression analysis, the odds ratio of having the MS when the participant consumed the MD was 0.81 (95% CI, 0.68-0.976), and when even a little to moderate PA (<7 kcal/min)was reported, the odds ratio was 0.75 (95% CI, 0.65-0.86). The higher levels of inflammation and coagulation markers among participants with MS did not explain much of the aforementioned effect of lifestyle modification. CONCLUSION: MS is common in Greece and is becoming even more common in the middle-aged population. The suggested therapeutic lifestyle approach may contribute to the reduction of the prevalence of the MS, beyond the levels of several lipid, inflammation, and coagulation markers.

The adoption of Mediterranean diet attenuates the development of acute coronary syndromes in people with the metabolic syndrome.

OBJECTIVES: In this work we investigated the effect of the consumption of the Mediterranean diet on coronary risk, in subjects with the metabolic syndrome. METHODS: During 2000-2002, we randomly selected, from all Greek regions, 848 hospitalised patients (695 males, 58 +/- 10 & 153 females, 65 +/- 9 years old) with a first event of acute coronary syndrome and 1078 frequency matched, by sex, age, region controls, without any suspicious for cardiovascular disease. Nutritional habits were evaluated through a validated questionnaire, while the metabolic syndrome was defined according to the NCEP ATP III criteria. Mediterranean diet was defined according to the guidelines of the Division of Nutrition/Epidemiology, of Athens Medical School. RESULTS: Of the 1926 participants, 307 (36.2%) of the patients and 198 (18.4%) of the controls (P < 0.001) met the ATP III criteria. This was related with 2fold adjusted coronary risk (odds ratio = 2.35, 95% 1.87-2.84) in subjects with the metabolic syndrome as compared with the rest of them. No differences were observed concerning the prevalence of the metabolic syndrome and sex of subjects, after adjustment for group of study (P > 0.1). Eighty (26%) of the patients and 70 (35%) of the controls (P < 0.01) with the metabolic syndrome were "closer" to the Mediterranean diet. Multivariate analysis revealed that the adoption of this diet is associated with a 35% (odds ratio = 0.65, 95% 0.44-0.95) reduction of the coronary risk in subjects with the metabolic syndrome, after adjusting for age, sex, educational and financial level and the conventional cardiovascular risk factors. CONCLUSION: Consequently, the adoption of Mediterranean diet seems to attenuate the coronary risk in subjects with the metabolic syndrome.

The association between physical activity and the development of acute coronary syndromes in treated and untreated hypertensive subjects.

The objective of this study was to evaluate the effect of physical activity on the risk of coronary events in different groups of hypertensive patients. During 2000-2001, 848 patients hospitalized for a first event of coronary heart disease and 1078 hospitalized controls without any suspicion of coronary heart disease, paired by sex and age, were randomly selected from all Greek regions. A total of 418 (49%) of the patients and 303 (28%) of the controls were classified as hypertensives, while 88 (21%) of the hypertensive patients and 88 (29%) of the hypertensive controls, reported regular leisure-time physical activity. Compared to physical inactivity, the analysis showed that light to moderate physical activity was associated with a reduction by 12% of the coronary risk in controlled hypertensive subjects (p=0.03), by 9% (p=0.04) in hypertensives who were untreated or unaware of their condition, and by 5% (p=0.087) in uncontrolled hypertensives. The practice of regular physical activity seems to be associated with lower coronary risk in various groups of hypertensives. However, these data cannot prove causality, and prospective studies will be necessary to confirm or refute the authors findings.

Risk stratification of coronary heart disease in Greece: final results from the CARDIO2000 Epidemiological Study.

BACKGROUND: In past years several risk factors have been associated with the incidence of coronary heart disease. The aim of this study was to investigate the associations between the risk of developing acute coronary syndromes and several risk factors in Greece. METHODS: During 2000-2002, 700 male (59 +/- 10 years old) and 148 female (65 +/- 9 years old) patients with the first event of an acute coronary syndrome were randomly selected from cardiological clinics of all Greek regions. Afterward, 1,078 population-based controls were randomly selected from the same hospitals and matched to the patients by sex and age. Detailed information regarding their medical and psychosocial status and various lifestyle habits related to coronary risk was recorded. RESULTS: The frequency ratio between males and females in the case series of patients was 4:1. The statistical analysis showed that smoking (odds ratio = 1.61, P < 0.001), hypertension (odds ratio = 1.99, P < 0.001), hypercholesterolemia (odds ratio = 3.53, P < 0.001), diabetes mellitus (odds ratio = 2.44, P < 0.01), family history of CHD (odds ratio = 3.19, P < 0.001), exposure to passive cigarette smoking (odds ratio = 1.54, P < 0.01), and depressive episodes (odds ratio = 1.35, P < 0.01) were associated with an increased coronary risk, while physical activity (odds ratio = 0.81, P = 0.01), adoption of Mediterranean diet (odds ratio = 0.80, P < 0.05), and high education (odds ratio = 0.81, P < 0.001) were associated with a significant reduction of the coronary risk. Also, a J-shape association was found between alcohol intake and coronary risk. CONCLUSION: Several emerging lifestyle risk factors (education, depression, diet, passive smoking), in addition to the conventional ones, may contribute to the risk of coronary events in this population.

The association of Mediterranean diet with lower risk of acute coronary syndromes in hypertensive subjects.

BACKGROUND: The elevation of blood pressure levels has been recognised as a determinant of the risk for several common cardiovascular diseases. In this work we examined the effect of Mediterranean type of diet on coronary risk in subjects with hypertension. METHODS: CARDIO2000 consisted of 848 randomly selected hospitalised patients (695 males, 58 +/- 10 years old; 153 females, 65 +/- 9 years old) for first event of coronary heart disease (CHD) and 1078 paired, by sex-age, hospitalised controls without CHD. The adoption of the Mediterranean diet was assessed through a validated questionnaire developed by the National School of Public Health. RESULTS: 418 (49%) of the patients and 303 (28%) of the controls were hypertensive. Of them 21 (5%) patients and 36 (12%) controls were unaware of their condition, 94 (22%) and 34 (11%) were untreated, 148 (35%) and 111 (36%) were uncontrolled and 155 (38%) and 122 (41%) were controlled (P<0.01). One hundred and sixty-two (19%) of the patients and 265 (25%) of the controls (P<0.01) adopted the Mediterranean type of diet. Our results suggest that the adoption of Mediterranean diet reduces the risk of developing acute coronary syndromes by 17% (odds ratio=0.83, 95% CI 0.73--0.88, P<0.01) in controlled hypertensive subjects, by 8% (odds ratio=0.92, 95% CI 0.87-0.95, P<0.05) in unaware, by 7% (odds ratio=0.93, 95% CI 0.88-0.95, P<0.05) in acknowledged but uncontrolled and by 20% (odds ratio=0.80, 95% CI 0.71-0.89, P<0.01) in normotensive subjects. CONCLUSION: According to our findings the adoption of the Mediterranean diet is associated with the reduction of coronary risk in hypertensive subjects.