Prusikova M

Impact of apolipoprotein A5 variants on statin treatment efficacy

AIMS Despite the fact that statin treatment efficacy is very high, there are substantial differences in treatment effectiveness among individuals. It is supposed that genetic predisposition plays an important role in these differences, but the contribution of individual polymorphisms is poorly understood. So far, more than 30 genes have been examined with ambiguous results. Apolipoprotein A5 is an important determinant of plasma lipid concentrations and its genetic variation could account for some of the observed differences in the response to statin therapy. However, this has not been analyzed before. MATERIALS AND METHODS We examined the putative association between APOA5 SNPs (c.-1131T>C, c.56C>G and c.457G>A) and efficacy during 3 months of statin treatment in 187 adult Caucasians. Patients were treated with low-dose (10 or 20 mg per day) simvastatin (46.3%), atorvastatin (40.5%) and lovastatin (13.2%). RESULTS The decrease in cholesterol was not significantly associated with the type or dose of statin. Carriers of the APOA5 genotype TT-1131 (n = 154) benefited more from statin treatment when compared with the C-1131 allele carriers (n = 33) (Delta low-density lipoprotein cholesterol: -36.3 +/- 15.1% vs Delta low-density lipoprotein cholesterol: -29.9 +/- 12.5%; p < 0.005, Mann-Whitney test). This result was independent of sex, age, BMI and APOE polymorphism. CONCLUSION Our results suggest that the APOA5 gene variants may play an important role in the pharmacogenetics of statin treatment.

A comprehensive guidelines-based approach reduces cardiovascular risk in everyday practice: the VARO study

Introduction The aim of study was to investigate the possibility of cardiovascular risk improvement through systematic identification of high-risk individuals and treatment in accordance with current guidelines using modern therapy in daily clinical practice. Material and methods Two hundred and sixty-three physicians participated in the study. The physicians were asked to screen for cardiovascular risk factors in patients presenting with unrelated problems and to re-evaluate the attainment of treatment goals in those with already known risk factors. Each physician enrolled up to 20 consecutive patients with hypertension and/or hyperlipidemia. A total of 3015 patients were included. Cardiovascular risk was assessed using the SCORE system. Risk factors were treated in accordance with current national guidelines. The therapy of hyperlipidemia and hypertension was preferentially based on rosuvastatin, amlodipine and valsartan. Further medication was at the discretion of the attending physician. Patients were examined at baseline and after 3 and 6 months. Results The principal result is that global cardiovascular risk decreased by 35% (from 8.9 ±6.4 to 5.9 ±4.4, p < 0.001). Systolic and diastolic blood pressure decreased by 12.5% (from 152 ±18 to 133 ±11, p < 0.001) and 11.4% (from 88 ±11 to 78 ±7, p < 0.001). The level of total cholesterol decreased 21% (from 6.3 ±1.2 to 5.0 ±0.9, p < 0.001) and the concentration of LDL-C decreased 28% (from 3.9 ±1.1 to 2.8 ±0.8, p < 0.001). HDL-C increased by 7% (from 1.43 ±0.58 to 1.53 ±0.56, p < 0.001) and triglycerides decreased by 25% (from 2.4 ±1.3 to 1.8 ±0.9, p < 0.001). Blood pressure and LDL-C target values were reached in 68% and 34%of patients, respectively. Conclusions The VARO study demonstrates that in daily practice settings, both individual risk factors and global cardiovascular risk are significantly improved through the systematic identification of high-risk individuals and their treatment in accordance with current guidelines using modern pharmacotherapy.

APOA5 haplotypes determine triglyceride decrease after lifestyle induced weight loss in children

Plasma levels of triglycerides (TG) are partially genetically determined and variants within the apolipoprotein A5 gene (APOA5, OMIM number 606368) have been shown to be the most important genetic determinants of TG levels [1,2]. In Caucasians, minor alleles of two tagging single nucleotide polymorphisms (SNPs), T-1131 > C [rs662799]; Ser19 > Trp [rs3135506] are associated not just with elevated TG levels, but also with cardiovascular risk and with the susceptibility to weight gain and obesity [3e5]. Plasma TG concentrations (and their response to an intervention) result from the interplay between genetic and environmental factors. Little is known about the interaction between these factors, especially in paediatric populations. We have analysed two tagging APOA5 SNPs in 357 Caucasian paediatric/adolescent obese patients (age 13.7 4.9 years, BMI 30.8 4.6 kg/m) who underwent an intensive one month in-patient weight reduction program. The program comprised individualized dietary changes to achieve daily caloric intake of 5000 kJ (age 8e10 years) or 7000 kJ (age 10e15 years). All participants were assessed by an exercise specialist and achieved five units of supervised endurance training daily (120 min, heart rate 65e75% of maximum). Lipid concentrations were assessed enzymatically (Hitachi, Japan). All parameters of interest; e.g. BMI, fasting TGs before and after the intervention and both APOA5 SNPs were available in 328 individuals. ANOVA was used for statistical analysis. Written informed consent was given by parents of participants. The study was approved by the institutional Ethics committee. At baseline, APOA5 haplotypes were associated with plasma TGs (P < 0.002 for haplotypes, P Z 0.08 for Ser19 > Trp and P < 0.01 for T-1131 > C), but neither with other lipids, nor with anthropometrical values. After the intervention, we observed a significant reduction of BMI by 2.3 0.7 kg/m (P < 0.001) and, also, of TGs by 0.25 0.42 mmol/L (P < 0.001).

LP-PLA2: A NEW MARKER OF CARDIOVASCULAR RISK

pared to normal-weight people with CVD (HR 2.33, 95%CI 1.25, 4.36, P=0.007). From the individual components of MetS, impaired fasting glucose (HR 1.5, 95% 1.23-1.92), hypertension (HR 1.1, 95% 1.03-1.47), dyslipidemia (HR 0.48, 95% 0.39-0.58) and central-obesity (HR 1.33, 95% 1.17-1.64) were all associated with increased CVD risk. Physical inactivity, smoking insulin-resistance, and low-grade inflammation were independently associated with CVD incidence. Conclusions: In contrast to normal-weight insulin-resistant people, MHO individuals show decreased CVD-risk in a 6-year follow-up study.