Angiotensin II type 1 receptor gene polymorphisms in patients with cardiac hypertrophy.

Chronic mechanical stress of the heart secondary to arterial hypertension is a primary cause of left ventricular hypertrophy (LVH). The renin-angiotensin system (RAS) plays an important role in the cardiovascular system, regulating the expression of cardiac hypertrophy, in part, independent of the effects of systemic hypertension. A major component of RAS is angiotensin converting enzyme (ACE), which is upregulated in pressure overload-induced cardiac hypertrophy as well as heart failure. In a recent study, we found that the T allele of the M235T polymorphism of the angiotensinogen gene in sporadic hypertrophic cardiomyopathy (HCM) patients is associated with LVH. The present study was designed to assess the contribution of the polymorphisms of the angiotensin II type 1 receptor (AGT1R A1166C) genes on development of left ventricular hypertrophy. Patients with hypertensive LVH and relatives of HCM without manifesting the disease, showed higher C allele frequency compared to patients with HCM (11.3% vs 4.2%, chi 2 = 5.3, p < 0.05 and 10.5% vs 4.2%, chi 2 = 5.3, p < 0.05, respectively), but healthy controls did not (11.3% vs 7.5%, chi 2 = 1.42, NS and 10.5% vs 7.5%, chi 2 = 1.2, NS). The strong interaction between ACE I/D and AGT1R A1166C gene polymorphisms has been found in groups of relatives of HCM patients; odds ratio associated with ACE D allele was significant in subjects carrying the AGT1R C allele (OR = 7.3, 95% CI 1.6-33.1; chi 2 = 7.9, p < 0.02) compared with healthy subjects. We conclude that the molecular variant of the AGT1R A1166C gene is not contributing to the development of cardiac hypertrophy in hypertensive LVH and HCM patients, whereas carriers of both C and D alleles had a four-fold increase in the odds ratio for family history of HCM without manifesting the disease.

Angiotensinogen gene polymorphism in Japanese patients with hypertrophic cardiomyopathy.

To examine the contribution of the renin-angiotensin system to hypertrophic cardiomyopathy (HCM), we studied 96 patients with HCM (mean age 50 years, 55% male), 105 of their unaffected siblings and offspring, and 160 healthy subjects without known hypertension and left ventricular hypertrophy (LVH) who were frequency matched to cases by age and sex. Patients were divided into familial or sporadic HCM (FHCM or SHCM) groups with or without affected members of their family. The region of interest in the angiotensinogen (AGT) gene, the missense mutation with methione-to-threonine amino acid substitution at codon 235 in angiotensinogen (M235T), was amplified by polymerase chain reaction with the use of allele-specific oligonucleotide primers flanking the polymorphic region of the AGT gene to amplify template deoxyribonucleic acid prepared from peripheral leukocytes. The T allele frequency was higher in the SHCM group than in unaffected siblings and offspring (88% vs 78%, X2 = 4.6, p < 0.05). The M allele frequency was higher in unaffected siblings and offspring than in patients with SHCM (23% vs 12%, X2 = 4.6, p < 0.05). The T allele frequency among unaffected siblings and offspring was similar to that observed in healthy subjects (78% vs 78%). We conclude that HCM, especially in sporadic cases, is partially determined by genetic disposition. The molecular variant of angiotensinogen T235 seems to be a predisposing factor for cardiac hypertrophy in HCM and carries an approximately twofold increased risk.

[Changes in the blood lipoprotein and apolipoprotein spectrum and the state of coronary channel in patients with unstable angina pectoris: a follow-up]. / Dinamika spektra lipoproteidov, apolipoproteinov plazmy krovi i sostoianie koronarnogo rusla u bol'nykh s nestabil'noi stenokardiei pri dlitel'nom nabliudenii.

The study was undertaken to examine 34 male patients with unstable angina pectoris who underwent coronary angiography (in the period of instability and at rehospitalization) and study of protein and lipid parameters in their plasma. During a follow-up (mean 33.9-2.2 months), the patients were divided into 2 groups according to the changes occurring in the coronary bed. These included: (1) patients with progressive atherosclerotic changes and (2) those with stabilization of the process. Changes in the lipid profile in patients with unstable angina were found to appear as profound atherogenic shifts in the spectrum of lipoproteins and apolipoproteins, which suggests that coronary atherosclerosis is progressive in the late period.

[Prognostic significance of various qualitative and quantitative indicators of coronary angiography in patients with unstable stenocardia]. / Prognosticheskoe znachenie nekotorykh kachestvennykh i kolichestvennykh pokazatelei koronarnoi angiografii u bol'nykh s nestabil'noi stenokardiei.

The coronary bed was qualitatively and quantitatively examined in 41 patients with unstable angina pectoris. The patients were divided into two groups: (1) those with uncomplicated angina and (2) those with complicated angina in relation of follow-up (mean 3.1 +/- 0.8 years) findings. In patients with a poor coronary heart disease outcome a symptom-related lesion was more frequently located mainly in the left coronary trunk during clinical manifestations of unstable angina pectoris, along with more severe overall lesion in the coronary bed. They had also higher incidence rates of complicated lesions and higher values of three quantitative parameters (stenosis extent, the mean and proper diameters of a stenotic segment in the symptom-related vessel) determined by semiautomatic stenosis configuration analysis.