Neusa Forti

Risk factors for atherosclerosis in children and adolescents with family history of premature coronary artery disease

OBJECTIVES To identify the prevalence of dyslipidemia in a group of 109 children and adolescents with a family history of premature coronary artery disease and to investigate the association between dyslipidemia and other risk factors for atherosclerosis. METHODS Total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides, body mass index, blood pressure, physical activity, smoking, per capita income and maternal schooling were investigated. RESULTS Total cholesterol and LDL-C levels were higher than desirable in 27.5% and 19.3%, respectively, of our patients; 13.8% had lower HDL-C values and 13.0% presented hypertriglyceridemia. Obesity and excess weight were observed in 25.7% of the cases. Out of these, 57.1% had abnormal lipid values. Dyslipidemia was observed in 38.5%, either alone or in combination with other risk factors. Smoking was observed in 3.6%, hypertension in 2.7% and physical inactivity in 72.5%. There was no relationship between dyslipidemia and per capita income, maternal schooling and physical inactivity. However, obesity and excess weight were identified as significantly associated with the occurrence of dyslipidemia (p = 0.02; odds ratio = 2.82, 95% CI = 1.6-6.81). CONCLUSION In children and adolescents with a family history of premature coronary artery disease, early identification of the risk factors for atherosclerosis is essential to allow the implementation of preventive measures.

Seven DNA polymorphisms at the candidate genes of atherosclerosis in Brazilian women with angiographically documented coronary artery disease.

The possible association of genetic markers at the apolipoprotein E (HhaI polymorphism), apolipoprotein B (XbaI, EcoRI and Ins/Del polymorphisms), and low-density lipoprotein receptor (LDLR) (AvaII, HincII and PvuII polymorphisms) with coronary artery disease (CAD) was evaluated in 50 Brazilian women with CAD diagnosed by angiography and in 100 healthy women (controls). The frequency of E3/E4 genotype for HhaI polymorphism at the Apo E gene was significantly higher in CAD patients than in controls (40% vs. 14%, respectively, P<0.001). Similarly, the X-X- genotype for XbaI polymorphism was more frequent in CAD individuals than controls (42% vs. 12%, P<0.0001). The A+A+ and P1P1 genotypes for AvaII and PvuII polymorphisms at the LDLR locus were also higher in CAD subjects than controls (44% vs. 16%, P<0.001 and 64% vs. 39%, P<0.05, respectively). The estimated relative risks for CAD in women carrying the E3/E4, X-X-, A+A+ and P1P1 genotypes were 4.1 [95% confidence interval (CI), 3.0-5.6], 5.3 (95% CI, 3.8-7.5), 4.1 (95% CI, 3.0-5.5), and 2.8 (95% CI, 2.2-3.6), respectively. This study demonstrates that Apo E, Apo B and LDLR gene polymorphisms are associated with CAD in Brazilian Caucasian women.

Leptin G-2548A promoter polymorphism is associated with increased plasma leptin and BMI in Brazilian women

Variants in leptin gene (LEP) have been implicated in the pathogenesis of obesity. The relationship between LEP G-2548A polymorphism and obesity-related traits was evaluated in a sample of Brazilian women (n = 228) who were randomly selected from two clinical centers in Sao Paulo city. Blood samples were collected for DNA extraction, plasma leptin and serum lipids measurements. LEP G-2548A genotypes were identified by a PCR- RFLP strategy using the endonuclease Alw44I. LEP G-2548A was associated with obesity after adjustment for covariates (age, hypertension, coronary artery disease, smoking and physical activity). Women carrying G allele had a four times higher risk of obesity than the A allele carriers (OR: 4.11, CI95%: 1.06-15.90, p = 0.041). G allele was also related to increased plasma leptin (p = 0.024) and body mass index (p = 0.027). Hypertension, hyperglycemia, dyslipidemia and coronary artery disease were associated with obesity. However LEP G-2548A polymorphism was not related to these variables. All together these data suggest that LEP G-2548A polymorphism has an important role in regulating plasma leptin levels and body mass index in women.

High-Density Lipoproteins: Metabolic, Clinical, Epidemiological and Therapeutic Intervention Aspects. An Update for Clinicians

Summary High density lipoproteins (HDL) constitute a class of heterogeneous lipoproteins with a complex, not fully understood metabolism, particularly concerning cholesteryl ester transfer protein (CETP) action and catabolism. HDLs are anti-atherogenic due to reverse cholesterol transport and to antioxidant, anti-inflammatory, anticoagulant, profibrinolytic and endothelial protection properties, (shown in vitro and in animals). Experimental, clinical, epidemiologic, and therapeutic intervention studies have shown that there is an inverse relationship between blood levels of these lipoproteins and the development of atherosclerotic disease in coronary arteries.Measures to increase plasma HDL-C levels, besides changes in lifestyle habits (an adequate selection of diet components, smoking cessation, regular practice of aerobic exercises) include lipid lowering drugs (LLDs). Drugs capable of inhibiting CETP are currently in advanced stages of development. Research is also being conducted with other drugs that act on different points of lipid metabolism.

Postprandial Lipemia: Influence of Aging

OBJECTIVE To investigate the behavior of postprandial lipemia assessed by means of repeated measurements of triglyceride levels in healthy individuals aged from 20 to 50 years, divided into the following 3 age groups: GI--from 20 to 30 years; GII--from 31 to 40 years; and GIII--from 41 to 50 years. METHODS Triglyceride levels were measured in 3 conditions: after a 12-hour fast, and 2 and 6 hours after a standard meal containing 40 g of fat. RESULTS The repeated-measures analysis of triglyceride levels showed a distinct behavior of the age groups throughout the 6 hours. The younger participants (GI) had a reduction in the triglyceride levels in the sixth hour; the elderly (GIII) had increasing values in the sixth hour; and those in the intermediate age group (GII) maintained their triglyceride levels, when comparing the second and sixth hours of blood collection. The differences in behavior were significant (P=0.01). CONCLUSION In a healthy adult population sample, aging influences the postprandial lipemia behavior.

Pvu II intron 15 polymorphism at the LDL receptor gene is associated with differences in serum lipid concentrations in subjects with low and high risk for coronary artery disease from Brazil.

Coronary artery disease (CAD) has a high prevalence in the Brazilian population. Nevertheless, studies of genetic risk factors for CAD in this country have not been sufficiently conducted. We used the Pvu II polymorphism (intron 15) at the low-density lipoprotein receptor (LDLR) gene to study the effect of variation at this locus in determining plasma lipid concentrations in 128 white subjects presenting a lipid profile suggesting high risk for CAD (HRG) and 100 white normolipidemic individuals (controls, CG). The Pvu II polymorphism was detected by PCR-RFLP. The P1P1 genotype for Pvu II polymorphism (homozygous for absence of restriction site) was greater in HRG individuals than in CG subjects (57% vs. 38%, P<0.05). Moreover, the P1P1 genotype was strongly associated with high concentrations of total cholesterol (P=0.0001), triglycerides (P=0. 0295), LDL-C (P=0.0001), and VLDL-C concentrations (P=0.0280) and lower HDL-C concentrations (P=0.0051) in HRG subjects. Similarly, the CG individuals with P1P1 genotype presented high concentrations of total cholesterol and LDL-C compared to other genotypes (P=0. 0001). This study demonstrates the influence of Pvu II polymorphism of the LDLR on serum lipid concentrations of individuals with low and high risk for CAD from Brazil.

Effects of Ava II and Hinc II polymorphisms at the LDL receptor gene on serum lipid levels of Brazilian individuals with high risk for coronary heart disease.

Coronary heart disease (CHD) has presented high prevalence in the Brazilian population. Nevertheless, studies of genetic risk factors for CHD in our country are insufficiently carried out. We have investigated the effects of Ava II (exon 13) and Hinc II (exon 12) polymorphisms at the low‐density lipoprotein receptor (LDLR) gene on circulating lipids of 170 white unrelated individuals presenting a lipid profile with high risk for CHD (HRG) and 130 controls (CG) from São Paulo City, Brazil. Ava II and Hinc II polymorphic regions at the LDLR gene were amplified by PCR and analyzed by enzymatic isotyping. The frequency of the genotypes A+A+ (Ava II) and H+H+ (Hinc II) was greater in HRG group compared to that of the controls (32 vs. 16% and 32 vs. 18%, respectively). Moreover, in the HRG group, A+A+ and H+H+ genotypes were associated with high concentrations of total cholesterol and LDL‐C in serum (P = 0.0001). Our results indicate that Ava II and Hinc II polymorphisms at the LDLR locus contribute to the variability of total cholesterol and LDL‐C levels in HRG individuals. These data suggest that the LDLR polymorphism remains a useful genetic marker for predicting CHD risk. J. Clin. Lab. Anal. 13:251–258, 1999.

Polymorphisms of the low-density lipoprotein receptor gene in Brazilian individuals with heterozygous familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a metabolic disorder inherited as an autosomal dominant trait characterized by an increased plasma low-density lipoprotein (LDL) level. The disease is caused by several different mutations in the LDL receptor gene. Although early identification of individuals carrying the defective gene could be useful in reducing the risk of atherosclerosis and myocardial infarction, the techniques available for determining the number of the functional LDL receptor molecules are difficult to carry out and expensive. Polymorphisms associated with this gene may be used for unequivocal diagnosis of FH in several populations. The aim of our study was to evaluate the genotype distribution and relative allele frequencies of three polymorphisms of the LDL receptor gene, HincII(1773) (exon 12), AvaII (exon 13) and PvuII (intron 15), in 50 unrelated Brazilian individuals with a diagnosis of heterozygous FH and in 130 normolipidemic controls. Genomic DNA was extracted from blood leukocytes by a modified salting-out method. The polymorphisms were detected by PCR-RFLP. The FH subjects showed a higher frequency of A+A+ (AvaII), H+H+ (HincII(1773)) and P1P1 (PvuII) homozygous genotypes when compared to the control group (P<0.05). In addition, FH probands presented a high frequency of A+ (0.58), H+ (0.61) and P1 (0.78) alleles when compared to normolipidemic individuals (0.45, 0.45 and 0.64, respectively). The strong association observed between these alleles and FH suggests that AvaII, HincII(1773) and PvuII polymorphisms could be useful to monitor the inheritance of FH in Brazilian families.

A method to detect the G894T polymorphism of the NOS3 gene. Clinical validation in familial hypercholesterolemia

Abstract An endothelial nitric oxide synthase gene (NOS3) polymorphism in exon 7 (G894T), resulting in Glu298Asp substitution at protein level, has been associated with myocardial infarction, hypertension and coronary atherosclerosis in some populations. This polymorphism is usually identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). However, the procedures described to date do not eliminate the possibility of misclassification and either require confirmation by DNA sequencing or are timeconsuming. In this study, a PCR-RFLP procedure to detect the G894T polymorphism at the NOS3 was optimized by the introduction of a constitutive cleavage site in the amplification product. This cleavage site provides an internal control for enzymatic activity to avoid mistyping. The method was validated by the study of 35 white unrelated individuals with familial hypercholesterolemia and 70 controls. The frequency of the variant allele (T) was similar between both groups (27% vs. 22%, NS), and comparable to the frequency found in other white populations. However, future studies are necessary to confirm these data. In summary, the optimized procedure for detection of the G894T NOS3 polymorphism is rapid, simple, and does not require confirmatory tests. Using this method, we found no association between this polymorphism and familial hypercholesterolemia.

Intervenção sobre tabagismo realizada por cardiologista em rotina ambulatorial

OBJETIVO: Avaliar a efetividade da intervencao sobre o tabagismo, realizada por medico cardiologista em rotina de ambulatorio, utilizando a prescricao de adesivos de nicotina. METODOS: Foram avaliados, consecutivamente, 100 pacientes (50 homens e 50 mulheres), incluindo consulta medica, aplicacao de escore para definicao do grau de dependencia a nicotina, determinacao da concentracao de monoxido de carbono expirado e peso corporeo. Os adesivos foram utilizados entre 8 e 12 semanas, com reducao progressiva da concentracao ate a suspensao (concentracoes de 21, 14 e 7mg) RESULTADOS: A taxa de abstinencia um ano apos o inicio do tratamento foi de 41%, confirmada pela concentracao do monoxido de carbono. CONCLUSAO: A intervencao sobre o tabagismo pode ser realizada em rotina de atendimento cardiologico com resultados satisfatorios. Os adesivos de nicotina sao seguros, bem tolerados, e devem ser utilizados, mais frequentemente, no auxilio aos fumantes, para deixarem de fumar.