Impact of cardiometabolic risk factors on major cardiovascular events in patients with familial combined hyperlipidemia.

BACKGROUND: Familial combined hyperlipidemia (FCH) is an inherited lipid disorder associated with premature cardiovascular disease. It has not been established whether the cardiometabolic risk factors, which frequently accompany FCH, such as diabetes, metabolic syndrome (MetS) and hypertension, modulate cardiovascular risk in FCH patients. METHODS AND RESULTS: In this single-center, retrospective study, 695 FCH patients with adequate follow-up were enrolled (mean age, 48.9 years; 455 male). Risk factors including lipid levels were evaluated before the initiation of treatment. Acute myocardial infarction (AMI) and cardiovascular death were recorded during a mean follow-up of 9 years. The combined endpoint (AMI and/or cardiovascular death) occurred in 41 patients (5.9% of the total). Those FCH patients who reached the combined endpoint had lower high-density lipoprotein cholesterol (HDL-C) than those who did not, but levels of other lipid variables were similar. Presence of hypertension, diabetes or MetS was a predictor of the combined endpoint on univariate Kaplan-Meier analysis (all P<0.005). Multivariate Cox proportional analysis showed that hypertension and MetS were associated with the combined endpoint independently of age, gender, HDL-C and presence of coronary artery disease at enrollment (adjusted hazard ratios [HRs], 3.00; 95% confidence interval [CI]: 1.46-6.17, P=0.003; HR, 2.43; 95CI%: 1.11-5.33, P=0.026, respectively). CONCLUSIONS: Cardiometabolic risk factors such as hypertension and MetS are independent predictors of major cardiovascular events in FCH patients.

Periodontal disease is associated with higher levels of C-reactive protein in non-diabetic, non-smoking acute myocardial infarction patients.

OBJECTIVES: A link between periodontal disease (PD) and cardiovascular events has been proposed, but confounding by shared risk factors such as smoking and diabetes remains a concern. We examined the prevalence of PD and its contribution to C-reactive protein (CRP) levels in acute myocardial infarction (AMI) patients and in subjects without AMI and with angiographically nonobstructive coronary disease in the absence of these confounding risk factors. METHODS: Periodontal status and admission CRP levels were evaluated in 87 non-diabetic and non-smoking subjects undergoing cardiac catheterization. The study group comprised of 47 patients with documented AMI, and 40 subjects without AMI and with angiographically nonobstructive coronary disease (ANCD group). RESULTS: Both the prevalence of PD and CRP levels were significantly higher in AMI patients compared with ANCD subjects (38.3% vs. 17.5%, p=0.03 and 44.3 vs. 8.5 mg/L, p<0.001 respectively). PD was associated with higher CRP levels in AMI patients (52.5 vs. 36.1 mg/L, p=0.04) as well as in ANCD subjects, however, in this group this was not significant (12.6 vs. 7.6 mg/L, p=0.5). Multivariable regression analysis confirmed two separate measures of PD as strong and independent contributors to elevated CRP levels in AMI patients (R2 = 0.28, R2 = 0.30, p=0.001). CONCLUSIONS: PD contributes to elevated CRP levels in non-diabetic, non-smoking AMI patients, independently of other confounding factors. These findings imply that periodontitis may emerge as a novel target for reducing future risk in AMI survivors.

Comparative value of simple inflammatory markers in the prediction of left ventricular systolic dysfunction in postacute coronary syndrome patients.

OBJECTIVES: We sought to assess the comparative value of inflammatory markers on the occurrence of left ventricular systolic dysfunction (LVSD) after an acute coronary syndrome (ACS). METHODS: During 2006-2008, 760 patients with an ACS were enrolled. C-reactive protein (CRP) and white blood cell (WBC) count were measured during the first 12 hours of hospital admission. RESULTS: CRP levels and WBC count were significantly higher in those who developed LVSD compared to those who did not. The analysis revealed that a 10 mg/dL increase of CRP levels and a 1000/microL increase in WBC are associated with a 6% and a 7% increase in the likelihood of developing LVSD, respectively. Furthermore, WBC count at entry and CRP have almost the same predictive value for development of LVSD after an ACS (R(2) = 0.109 versus R(2) = 0.093). CONCLUSIONS: Serum CRP levels and WBC count at entry are almost equally powerful independent predictors of LVSD, after an ACS.

Chronic systemic inflammation accompanies impaired ventricular diastolic function, detected by Doppler imaging, in patients with newly diagnosed systolic heart failure (Hellenic Heart Failure Study).

We sought to evaluate the relationship between plasma cytokine levels (sCD14, tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6) and tissue Doppler derived indices of left ventricular systolic and diastolic function in patients with newly diagnosed heart failure. We enrolled 101 consecutive patients (mean age 65+/-13 years) with newly diagnosed heart failure who were hospitalized in our institute. Echocardiographic assessment was performed in all patients during the third day of their initial hospitalization. The pulsed tissue Doppler imaging (TDI) of the systolic and diastolic function of mitral annulus was characterized by the systolic wave Smv, and the diastolic waves: Emv and Amv. Left atrial kinetic energy (LAKE), an index of left atrial function, was calculated using the equation 1/2 x LASV x 1.06 x Amv(2); where LASV is left atrial systolic volume. Furthermore the ratio E/Emv and the flow propagation velocity were also calculated; where E is the rapid mitral filling wave, detected by pulse Doppler. Soluble plasma levels of CD14, TNF-alpha, and IL-6 were measured in all patients during their third day of hospitalization. Linear regression analysis, after adjustment for sex, age, left ventricular ejection function, body mass index, arterial hypertension, smoking, physical activity, creatinine clearance, diabetes mellitus, and blood lipid levels, revealed that IL-6 levels were inversely associated with LAKE (b= - 5422.4+/-2031.5, P=0.03), Sm (b= -0.375+/-0.1, P=0.03), and flow propagation (b= -5.404+/-0.621, P=0.001). CD14 levels were inversely associated with flow propagation (b = -17.655+/-2.6, P=0.001), and positively associated with E/Emv ratio (b=2.58+/-3.6, P=0.002) and A/Amv ratio (b=0.629+/-0.6, P=0.04). TNF-alpha was inversely associated with Smv (b-1.189+/-0.3, P=0.005). This study reveals that increased plasma levels of CD14, IL-6 and TNF-alpha are associated with impaired left atrial function and more advanced left ventricular diastolic and systolic dysfunction, in patients with newly diagnosed heart failure.

The impact of ezetimibe and high-dose of statin treatment on LDL levels in patients with heterozygous familial hypercholesterolemia.

We evaluated the efficacy and the safety of combining high doses of statins and ezetimibe in heterozygous familial hypercholesterolemia (hFH) patients. Seventy patients with hFH, received 10 mg of ezetimibe, in addition to their current statin therapy and were followed up for twelve months. The co-administration of statins and ezetimibe improved total cholesterol (p<0.05), LDL-c(p<0.05), triglycerides (p<0.05) and apolipoprotein-B (p<0.05) in comparison to statin monotherapy. There were no changes in high density lipoprotein cholesterol (HDL-c), apolipoprotein-A, lipoprotein (a), fibrinogen and C-reactive protein (CPR). In conclusion the combination of 10 mg of ezetimibe with high dose statin therapy is effective in hFH, offering a further reduction of LDL-c throughout the 12 months of follow up.

Prevalence and determinants of coronary artery disease in males and females with familial combined hyperlipidaemia.

BACKGROUND: Familial combined hyperlipidaemia (FCH) is an inherited dyslipidaemia that is related to a high risk of coronary artery disease (CAD). We evaluated the prevalence of CAD in a large FCH population and the association of risk factors with CAD according to gender. METHODS: In this single-center, observational study, lipid and lipoprotein variables were measured in untreated patients with FCH (565 males and 302 females). CAD was defined as a documented history of myocardial infarction or coronary revascularization, or an abnormal coronary angiogram (stenosis of >50% in an epicardial coronary artery), or angina plus abnormal imaging stress test. RESULTS: Males had higher triglyceride level (P<0.001) but lower total cholesterol (P<0.001) and HDL-cholesterol level (P<0.001) compared to women. The prevalence of CAD was 22.2% in men and 4.6% in women (P<0.001). In logistic regression analysis, male gender was associated with a higher risk of CAD independent of lipid parameters and other risk factors (adjusted ORs for CAD 9.4, P<0.001). In gender-specific analysis, age (OR=1.06 per 1-year increase, P<0.001), diabetes (OR=2.42, P<0.01) and Lp(a) (OR=1.09 per 1-mg/dL increase, P<0.01) were independent predictors of CAD in men. In women, age (OR=1.24, P<0.01), total cholesterol (OR=1.022 per 1-mg/dL increase, P<0.05) and fasting glucose (OR=1.031 per 1-mg/dL increase, P<0.05) were independently associated with CAD. CONCLUSIONS: In FCH patients, the prevalence of CAD is higher in males than in females, independent of lipidaemic profile and other risk factors. Among lipid variables, Lp(a) and cholesterol level are predictors of CAD in males and females respectively.

The association between pre-hypertension status and oxidative stress markers related to atherosclerotic disease: the ATTICA study.

BACKGROUND: We sought to evaluate the association between pre-hypertension status and oxidative stress markers (total antioxidant capacity (TAC) and oxidized low density lipoprotein (LDL)), in a random sample of cardiovascular disease-free adults. METHODS: The ATTICA study is a cross-sectional population-based survey that conducted in Attica region during 2001-2002. Based on a multistage and stratified random sampling, 1514 men and 1528 women (18-89 years old) were enrolled. The survey included a detailed interview; blood samples collected after 12h of fasting and, among other clinical measurements, status of blood pressure levels was evaluated. RESULTS: Six hundred and fifty-three men (43%) and 535 women (35%) were defined as pre-hypertensives. Both systolic and diastolic blood pressures were inversely correlated with TAC (p<0.001) and positively correlated to oxidized LDL (p<0.001). Particularly, compared to normotensive subjects, pre-hypertensives had 7% lower TAC levels (p<0.001) and 15% higher oxidized LDL levels (p<0.05), after correcting for multiple comparisons and adjusting for age, body mass index, blood lipids, glucose, food groups consumed and other potential confounders. CONCLUSIONS: Studying a large sample of cardiovascular disease-free adults, we revealed an association of pre-hypertension with oxidative stress markers linking to atherosclerotic process.

Metabolic syndrome prevalence and characteristics in Greek adults with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCH) is closely related with metabolic syndrome (MetSyn), and coronary artery disease (CAD) is positively associated to MetSyn and FCH. In this study, we evaluated the prevalence of MetSyn and its components between patients with FCH and a control group. We also investigated the role of MetSyn and diabetes mellitus (DM) on the incidence of CAD within the FCH group. Our study population consisted of 463 male and 243 female patients with FCH who were not receiving any hypolipidemic treatment, and 1128 men and 1154 women who came from the same geographical region. The prevalence of MetSyn was 42% and 19.8% among FCH subjects and controls, respectively, whereas MetSyn increased with age in both groups. The prevalence of CAD was 15.3% in the FCH group. Moreover, after dividing FCH patients into 3 subgroups, with and without MetSyn and with DM, CAD prevailed at a percentage of 15.2%, 11.1%, and 26.5%, respectively. However, statistically significant differences in the prevalence of CAD were observed only between FCH subjects with DM compared with the other 2 subgroups, even when an adjustment for age, sex, and smoking was conducted. People with FCH and MetSyn differed in several anthropometric, biochemical, and clinical characteristics, compared with the non-MetSyn subgroup of FCH. MetSyn is more prevalent in the FCH than in the control group. Among subjects with FCH, only DM was significantly associated with an increase in the prevalence of CAD in this subgroup compared with FCH individuals with or without MetSyn.

Evidence that non-lipid cardiovascular risk factors are associated with high prevalence of coronary artery disease in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia.

BACKGROUND: Heterozygous familial hypercholesterolemia (hFH) and familial combined hyperlipidemia (FCH) have been associated with increased risk for coronary artery disease (CAD), but the impact of traditional risk factors to the incidence of CAD in these patients remains unknown. The present study evaluates the contribution of such risk factors to the development of CAD in these two dyslipidemic populations. METHODS: This cross-sectional study enrolled a total 1306 subjects; 600 individuals with hFH (mean age 41+/-13 years, 261 males and 339 females), and 706 individuals with FCH (mean age 49+/-11 years, 463 males and 243 females). Blood samples were collected after 12 hours fasting period, and serum lipids were determined. Multivariate logistic regression models were used to estimate the odds ratios of CAD based on the type of hyperlipidemia, after adjustment for demographic characteristics and risk factors. RESULTS: Subjects with FCH were older (P<0.001), and they had a significantly increased prevalence of hypertension, diabetes and metabolic syndrome (40 vs. 10%, 13 vs. 2% and 41 vs. 6% respectively, all P<0.001) compared to the hFH group. Total cholesterol, LDL-cholesterol, and apolipoprotein B levels were higher (all P<0.001) in hFH subjects. Although in multivariate analysis lipid abnormalities found in hFH were associated with increased risk of CAD (P<0.001) compared with lipid abnormalities of FCH, the overall prevalence of CAD was similar between the two groups (16.7 vs. 15.3%, P=NS). CONCLUSIONS: Despite the high atherogenic potential of altered lipid metabolism found in hFH, the prevalence of CAD is similarly increased in patients with hFH or FCH. This may be related to the clustering of non-lipid cardiovascular risk factors, such as diabetes mellitus, observed in patients with FCH.

Status and management of hypertension in Greece: role of the adoption of a Mediterranean diet: the Attica study.

OBJECTIVE: To evaluate the prevalence, awareness, treatment, and control of hypertension, in a random sample of adults free of cardiovascular disease, in Greece. A secondary goal was to evaluate the association between hypertension status and adoption of the Mediterranean diet. DESIGN: Cross-sectional survey. PARTICIPANTS: On the basis of multistage sampling, 1,128 men and 1,154 women older than 18 years were enrolled. MAIN OUTCOME MEASURES: The survey included a detailed interview and, among other clinical measurements, status and management of blood pressure were recorded. Adoption of the Mediterranean diet was assessed through a special questionnaire. RESULTS: The prevalence of hypertension was 38.2% in men and 23.9% in women (P < 0.05). The majority of men (65%) and women (40%) were untreated, and of those who were treated, only 109 of 319 (34%) had their blood pressure adequately controlled. Thus only 15% of the hypertensive population had their blood pressure well controlled. Multivariate logistic regression analysis revealed that consumption of a Mediterranean diet was associated with a 26% (odds ratio = 0.74, P = 0.008) lower risk of being hypertensive, and with a 36% (odds ratio = 1.36, P = 0.021) greater probability of having the blood pressure controlled. CONCLUSIONS: A considerable proportion of the general population remain unaware of having hypertension or do not have their blood pressure well controlled. However, consumption of a Mediterranean type of diet seems to reduce rates of hypertension in the population, and may contribute to the control of hypertension at the population level.

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.