CAROLINA PEREIRA
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- The removal from plasma of chylomicrons and remnants is reduced in heterozygous familial hypercholesterolemia subjects with identified LDL receptor mutations: Study with artificial emulsions(2012) CARNEIRO, Marcia M.; MINAME, Marcio H.; GAGLIARDI, Ana C.; PEREIRA, Carolina; PEREIRA, Alexandre C.; KRIEGER, Jose E.; MARANHAO, Raul C.; SANTOS, Raul D.Chylomicron remnants bind to both their specific receptors (LRP) and to the LDL receptor (LDLR) in the liver. There is controversy whether disturbances of chylomicron metabolism occur in subjects with familial hypercholesterolemia (FH). The aim of this study was to evaluate whether there are defects on the removal from plasma of chylomicrons and their remnants in heterozygous FH patients with determined LDLR mutations. We studied 20 heterozygous FH patients (43.2 +/- 12 years old, 60% males) and 50 normolipidemic subjects matched for age and gender. FH subjects were not in use of LDL-lowering drugs for at least 6 weeks. The removal from plasma of chylomicrons and their remnants was measured by isotopic decay after venous injection of a chylomicron-like emulsion radiolabeled with C-14-cholesteryl ester (C-14-CE) and H-3-triolein (H-3-TO). These track respectively removal from plasma of chylomicrons and remnants and lipolysis. There was a significant reduction in the fractional catabolic rates (FCR in h(-1)) of C-14-CE in FH in comparison with normolipidemics: 0.048 (1.46.10-7; 0.57) vs. 0.71(0.049; 1.62), [median (25th-75th percentile)], p = 0.003. No differences were found in FCR of H-3-TO between FH and controls, respectively 1.62 (1.02; 2.331) and 1.914 (1.34; 2.878), p = 0.405. In conclusion heterozygous FH subjects had a significant decrease on the removal from plasma of chylomicrons and their remnants compared with normolipidemics.
- Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia(2014) PEREIRA, Carolina; MINAME, Marcio; MAKDISSE, Marcia; KALIL FILHO, Roberto; SANTOS, Raul D.Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL-c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). Objective: This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. Methods: The diagnosis of PAD was established by ankle-brachial index (ABI) values <= 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 +/- 14 years and total cholesterol levels of 342 +/- 86 mg/dL. Results: The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Conclusion: Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.
- Peripheral arterial disease in heterozygous familial hypercholesterolemia(2015) PEREIRA, Carolina; MINAME, Marcio H.; MAKDISSE, Marcia R. P.; WATANABE, Carolina; PESARO, Antonio E.; JANNES, Cinthia E.; KALIL FILHO, Roberto; PEREIRA, Alexandre C.; SANTOS, Raul D.Background: Familial hypercholesterolemia is characterized by elevated plasma cholesterol and early coronary arterial disease onset. However, few studies investigated the association of heterozygous familial hypercholesterolemia with peripheral arterial disease. Methods: In a cross sectional study 202 heterozygous familial hypercholesterolemia patients (91% confirmed by molecular diagnosis) were compared to 524 normolipidemic controls. Peripheral arterial disease was diagnosed by ankle-brachial index values <= 0.90. Results: Compared with controls, familial hypercholesterolemia patients were older, more often female, with higher rates of hypertension, diabetes, previous coronary disease and higher total cholesterol levels. Smoking (previous and former) was more common among controls. The prevalence of peripheral arterial disease was 17.3 and 2.3% respectively in familial hypercholesterolemia and controls (p < 0.001). Results persisted after matching familial hypercholesterolemia and controls by a propensity score. Regression analyses demonstrated that age (odds ratio-OR = 1.03 95% CI 1.00-1.05, p = 0.033), previous cardiovascular disease (OR = 3.12 CI 95% 1.56-6.25, p = 0.001) and familial hypercholesterolemia diagnosis (OR = 5.55 CI 95% 2.69-11.44, p < 0.001) were independently associated with peripheral arterial disease. Among familial hypercholesterolemia patients, age (OR 1.05, 95% CI 1.02-1.09, p = 0.005), intermittent claudication (OR 6.32, 95% CI 2.60-15.33, p < 0.001) and smoking (OR 2.44, 95% CI 1.08-5.52, p = 0.032) were associated with peripheral arterial disease. Conclusions: Peripheral arterial disease is more frequent in familial hypercholesterolemia than in normolipidemic subjects and it should routine screened in these individuals even if asymptomatic. However, its role as predictor of cardiovascular events needs to be ascertained prospectively.