To examine the contribution of six cardiovascular polymorphisms to the occurrence of a first event of ischemic heart disease (IHD) in a primary care population with a high prevalence of hypertension. Furthermore, we specified the data for sex and age.In this cross sectional case-control study, patients with a first event of IHD (157) and event-free controls (571) were studied. Both the groups were genotyped for the angiotensin II type 1 receptor (A1166C), angiotensinogen (M235 T), angiotensin converting enzyme (4656rpt), endothelial nitric oxide synthase (E298D), G-protein beta3 subunit (C825 T), and alpha-adducin (G460W) polymorphisms. Univariate and multivariate odds ratios (ORs) were calculated to assess the association between a first ischemic event and these polymorphisms. Sliding mean analyses were performed to show age-specific associations.Multivariate ORs indicated a protective association for the carrier status of the T-allele of AGT, overall [OR = 0.69 (0.34-0.90)] and for males [OR = 0.58 (0.27-0.89)]. Sliding mean analyses showed a continuous protective association with IHD of the T-allele of AGT with increasing age in males, whereas in females an increased risk for IHD was observed with a maximum OR of 1.6 at the age of 56 years.In this population the T-allele of the AGT polymorphism is protective for a first event of IHD in males.
In a primary care population covering a broad spectrum of cardiovascular risk (HIPPOCRATES project) the relationship between carotid intima-media thickness (CIMT) and six cardiovascular polymorphisms were analyzed in a cross-sectional study.CIMT was assessed in 618 participants, who were genotyped for the AGTR1 (A1166C), AGT (M235T), ACE (4656(rpt)), NOS3 (E298D), GNB3 (C825T) and ADD1 (G460W) polymorphisms. Linear regression analyses were performed to assess the relationship between CIMT and the polymorphisms.The study population included 289 men (46.8%) and 329 (53.2%) women of whom 52.3% were treated with cardiovascular medication. CIMT was significantly associated with age, female sex, use of cardiovascular medication, waist circumference and dyslipidemia. After correction for these covariates, multivariate linear regression analyses showed that only in women the C-allele of AGTR1 was associated with a thicker CIMT (P = 0.03). The T-allele of ADD1 was associated with a smaller CIMT in both men and women, but this only reached statistical significance in women (P = 0.03).Although the effect of both genetic variants on CIMT was small, this study showed a statistically significant effect of AGTR1 and ADD1 in women. However, our findings should be viewed as hypothesis-generating and require further confirmation in prospective epidemiological primary care studies.
Background Several studies have assessed the relationship between the angiotensin-converting enzyme (ACE) I/D or angiotensin II type 1 receptor (AT1R)-A1166C polymorphisms and blood pressure (BP). Since most data have been obtained in selected populations, the present study was performed in a healthy normotensive primary care population. Objective To investigate the individual effects of the aforementioned polymorphisms and their interaction on BP. Methods This cross-sectional study included 198 healthy subjects. Office BP was measured and polymorphisms were genotyped (polymerase chain reaction). Polymorphism interaction was tested using the following model: systolic blood pressure (SBP) (or diastolic blood pressure, DBP) = b0 + b1X + b2Y + b3XY, in which X and Y represent the polymorphisms' risk alleles. Results The ACE I/D polymorphism was associated with SBP (P = 0.002) and DBP (P = 0.004); highest pressures tracked with the DD genotype. Furthermore, in multiple linear regression analysis the ACE D allele was associated with SBP (P = 0.005) and DBP (P = 0.001), when adjusted for body mass index (BMI) and age. With respect to the AT1R-A1166C polymorphism, SBP was highest in the CC genotype (P = 0.025). In linear regression analysis the C allele was not associated with SBP. No synergistic effect of ACE D and AT1R C alleles on BP was found. Nevertheless, highest DBP tracked with the DDCC combination in comparison with other homozygous allele combinations (P = 0.030). Conclusions This study confirmed an association of ACE I/D and AT1R-A1166C polymorphisms with BP in a healthy normotensive primary care population. Although synergistic effect of both polymorphisms on BP does not seem to be present, an additive effect on DBP is likely.
Methods: Prospective study in 51 patients (58±16 years, 31% male) with stable angina and myocardial ischemia in non-invasive tests, submitted to elective coronary angiography.Virtual histology data were obtained by intra-coronary ultrasound with a 30 mHz probe and analysed with the VolcanoTM system.This system codes by colours four types of plaque composition (Fibrous -F, Fibro-lipidic -FL, Necrotic -N and Calcified -C).Plaques with at least 25% of fibro-lipidic component were considered as predominant fibro-lipidic plaques (11 patients) and these patients were compared in terms of age, gender, risk factors for coronary artery disease and quantitative vessel characteristics (vessel diameter, lumen diameter, lumen area, plaque area and calcium percentage).Results: In this population, 71% were hypertensive patients, 27% diabetics, 27% smokers and 67% had hyperlipidemia.In hypertensive patients (vs nonhipertensive), mean composition of the plaque (in percentage) was: F 58% vs 59%, FL 15% vs 18%, N 16% vs 14%, C 11% vs 9%, Mann-Whitney p=NS.In diabetics (vs non-diabetics): F 58% vs 58%, FL 12% vs 17%, 17% vs 15%, C 13% vs 9%, p=NS.In smokers (vs non-smokers): F 63% vs 56%, FL 18% vs 15%, N 16% vs 12%, C 7% vs 12%, p=NS.In patients with hyperlipidemia (vs normal lipid profile): F 56% vs 62%, FL 17% vs 14%, N 16% vs 14%, C 11% vs 9%, p=NS.When we compare patients with predominant FL plaques, there were no statistical significant differences, except for the percentage of calcium (4% in FL vs 13% in the remaining patients, p=0.02).Also the presence of smoking was associated with a FL predominant plaque (OR 4.8, p=0. 05).Conclusions: There was no difference in plaque composition according to each risk factor.Fibro-lipidic plaques were more frequent in smokers with a consequent higher risk for acute coronary events.Calcium in these plaques has a smaller percentage, which could suggest less chronicity of those lesions.
To examine in a population with a high prevalence of hypertension, the association between six cardiovascular polymorphisms, arterial stiffness and medication use.In this cross-sectional study (Hypertension: Interaction and Prevalence of POlymorphisms related to Cardiovascular Risk and the Association to Treatment Efficacy Study project), arterial stiffness was assessed by measuring pulse wave velocity (PWV) in 575 patients in one primary care practice. Patients were genotyped for the angiotensin II type 1 receptor [AGTR1 (A1166C)], angiotensinogen (M235T), angiotensin-converting enzyme (4656rpt), endothelial nitric oxide synthase (E298D), G-protein beta3 (C825T), and alpha-adducin (G460W) polymorphisms. Linear regression analyses were performed to assess the association between polymorphisms and PWV.Thirty percent of the patients (273 men, 302 women) had a carotid-femoral pulse wave velocity above 12 m/s and more than 60% of the patients had a carotid-femoral/carotid-radial PWV (CF/CR ratio) above 1. The CF/CR ratio was significantly associated with age, sex, dislipidemia, cardiovascular medication use and pulse pressure. After correction for these covariates, multivariate linear regression analyses showed that the C allele of AGTR1 was associated with a lower CF/CR ratio. This association was significantly influenced by cardiovascular medication use (P = 0.011), and showed a dose-allele effect, the CF/CR ratio decreasing with the number of C alleles (P = 0.04).In a primary care population, this study showed an independent protective dose-allele effect for the presence of C alleles of the AGTR1 polymorphism on PWV. This association, which was influenced by the use of cardiovascular medication, needs further investigations to identify the underlying mechanisms.
