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 enrolment (adjusted hazard ratios [HRs], 3.00; 95% confidence interval [Cl]: 1.46-6.17, P=0.003; HR, 2.43; 95C1%; 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. (Circ J 2013; 77: 163-168

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

Background; Familial combined hyperlipidaemia (FCH) is all inlicrited dyslipidaernia 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 accordino to gender. Methods: In this single-center, observational study, lipid and lipoprotein variables were measure in untreated patients with FCH (565 males and 302 females). CAD was defined as a documented history of myocardial infarction or coronary revascularization, or all abnormal coronary angiogram (stenosis of >50% in in 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. (C) 2007 Elsevier Ireland Ltd. All rights reserved

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. (C) 2008 Elsevier Ireland Ltd. All rights reserved

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 FCFL This may be related to the clustering of non-lipid cardiovascular risk factors, such as diabetes mellitus, observed in patients with FCH. (C) 2006 Elsevier Ireland Ltd. All rights reserved