Association of genetic polymorphisms with endothelial dysfunction in chronic heart failure.

OBJECTIVES: Endothelial dysfunction can be shown very early in the cardiovascular disease. In the present study the association between congestive heart failure (CHF), endothelial function and 3 gene polymorphisms was investigated. PATIENTS AND METHODS: In 104 healthy controls and 104 CHF patients, endothelial constitutive nitric oxide synthase (ecNOS), angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) gene polymorphisms were assessed. The cause of CHF was ischemic in 68 patients and dilated cardiomyopathy (DCMP) in 36 patients. High resolution brachial artery ultrasound was used in 37 CHF patients and 37 healthy controls to assess the endothelial function. Endothelium-dependent vasodilation (EDD) and endothelium-independent vasodilation (EID) were determined. RESULTS: There no was difference between controls and CHF patients for the ACE, ecNOS, and AT1R genotype frequencies. Compared to controls CHF patients had significantly impaired EDD (9.0+5% vs 16±7%, p < 0.001) and EID (13±6% vs 19+8%, p = 0.001). EDD (7±4% vs 12+6%, p = 0.005), but not EID, was significantly impaired in ischemic CHF as compared to DCMP patients. In the CHF group ecNOS a allele and AT1R C allele influence the EDD. CONCLUSIONS: Endothelial dysfunction was present in CHF group and the presence of ecNOS a allele and AT1R C allele further impaired EDD.

Endothelial constitutive nitric oxide synthase, angiotensin converting enzyme, angiotensin II type 1 receptor gene polymorphisms and endothelial functions in healthy individuals.

INTRODUCTION: Endothelial dysfunction is recognized as an early and initiating event in the pathogenesis of coronary artery disease. Gene polymorphisms of endothelial constitutive nitric oxide synthase (ecNOS), angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) have been found to be associated with atherosclerosis.  We aimed to investigate the possible effects of ecNOS, ACE and AT1R gene polymorphisms on endothelial functions in healthy population. MATERIALS AND METHODS: In 255 healthy subjects (male/female: 119/136 mean age 35.1±2.3 years)  ecNOS, ACE and AT1R gene polymorphisms were assessed by polymerase chain reaction (PCR). Endothelium dependent (EDD, flow-mediated) and endothelium independent vasodilation (EID) were measured by high resolution brachial artery ultrasound and 0.5 mg sublingual nitroglycerine respectively. RESULTS: ecNOS and ACE genes had no significant effect on EDD and EID. However, subjects with AT1RAC+CC genotypes had lower EDD compared to subjects with AT1RAA genotype in females (19.4 ± 6.6% vs 21.5 ± 7.8%, p = 0.041). EDD and EID were significantly negatively associated with  age, body mass index, serum creatinine, glucose, uric acid and hemoglobin levels. When the data on age, uric acid, BMI, glucose, creatinine, and hemoglobin were split into 3 as low-1/3, mid-1/3 and  high 1/3, there was significant graded decrease in EDD and EID with these parameters. In multiple regression analysis, age and presence of AT1RAC+CC genotype  retained as significant independent factors predicting endothelial functions. CONCLUSIONS: Gene polymorphisms of endothelial constitutive nitric oxide synthase and  angiotensin converting enzyme had no effect on endothelial functions. However, the presence of angiotensin II type 1 receptor polymorhism (AT1RAC+CC genotype) seemed to adversely affect the endothelial functions as reflected by impaired endothelium dependent and independent vasodilatation in healthy individuals.

Drugs with blocking effects on the renin-angiotensin-aldosterone system do not improve endothelial dysfunction long-term in hypertensive patients.

In essential hypertension, endothelial dysfunction has been documented many times and correlates with prognosis. The influence of the renin-angiotensin-aldosterone system (RAAS) on endothelial dysfunction has also been studied. The present study investigated the duration of the effects of RAAS-blocking drugs on endothelial function in 44 consecutive, never-treated, outpatients with mild to moderate hypertension. Patients (11 per group) received an angiotensin receptor blocker (ARB; irbesartan 300 mg/day or valsartan 160 mg/day) or an angiotensin-converting enzyme inhibitor (ACEi; fosinopril 10 mg/day or quinapril 20 mg/day). If target blood pressure (< 140/90 mmHg) was not achieved, 12.5 mg/day hydrochlorothiazide was added. Endothelial function, assessed by measuring brachial artery diameter, did not change significantly after 6 weeks, 1 year or 3 years of treatment in any group. Across all groups, endothelium-dependent and -independent vasodilation increased significantly after 6 weeks but, after 1 year, decreased below baseline and was at a similar level after 3 years; groups did not differ significantly. Both ACEi and ARB had similar effects on endothelial function; improvement occurred at the start of treatment but was not maintained. Endothelial dysfunction may be a resistant or irreversible feature of hypertension, requiring high doses of antihypertensive drugs and above-average patient compliance.

Precipitating factors for systolic and diastolic heart failure: a four-year follow-up of 192 patients.

OBJECTIVES: To investigate precipitating factors for systolic and diastolic heart failure. DESIGN: Prospective study. PATIENTS AND METHODS: The study population consisted of 192 patients with heart failure treated for 536 episodes of acute decompensation of heart failure from 1998 to 2002. The patients were classified as having systolic or diastolic heart failure, and grouped according to aetiology and precipitating factors. RESULTS: Coronary heart disease was the most common cause of systolic heart failure, whereas rheumatic heart disease was the most frequent cause of diastolic heart failure. The most important precipitating factors in systolic heart failure were infections (38%), arrhythmias (35%), and vascular causes (24%), whereas the precipitating factors in diastolic heart failure were infections (50%), arrhythmias (46%), and uncontrolled hypertension (26%). Avoidable precipitating factors in systolic and diastolic heart failure were noted in 34% and 68% of cases, respectively. CONCLUSIONS: Better patient education and better follow-up of patients by physicians according to the most recent guidelines may decrease the frequency of heart failure events and consequent morbidity and mortality.

The diagnostic value of troponin T and myoglobin levels in acute myocardial infarction: a study in Turkish patients.

This study compares the diagnostic value of troponin T (TnT) and myoglobin with creatinine kinase (CK) for myocardial infarction (MI) in a tertiary care centre in a developing nation. The study group comprised 33 acute myocardial infarction patients and 27 healthy controls. Receiver operating characteristic curves for TnT, myoglobin and CK were drawn and areas under the curve calculated. At admission, myoglobin levels had greater diagnostic sensitivity than TnT or CK levels. After 2 h, myoglobin and TnT had equal sensitivity and specificity, whereas CK still had lower sensitivity than myoglobin and TnT. After 4 h there was no difference between the tests. It was concluded that myoglobin levels on admission and TnT at 2 h had the greatest diagnostic rate, whereas all the tests were similar after 4 h for MI.

Risk factors for coronary heart disease in patients with spinal cord injury in Turkey.

OBJECTIVE: To compare the standard risk factors for coronary heart disease (CHD), defined in National Cholesterol Education Program II (NCEP II) of Turkish spinal cord injury (SCI) patients with healthy controls, discuss the results according to the findings in Turkish population, and SCI patients in the literature. DESIGN: We assessed 52 age and sex matched healthy control subjects, and 69 SCI patients (16 females, 53 males with the mean age of 33.9+/-11.37 years) with time since injury of 12.8+/-13.45 months. The study consisted of 45 paraplegics, and 24 tetraplegics with 54% incomplete, and 46% complete injury. RESULTS: Risk factors for CHD according to NCEP II were; age and sex in 16%, positive family history in 0%, cigarette smoking in 54%, hypertension (HT) in 0%, high total cholesterol (TC) in 32%, high low-density lipoprotein cholesterol (LDL) in 41%, low high-density lipoprotein cholesterol (HDL) in 52%, and diabetes mellitus (DM) in 7% of our SCI patients, respectively. Compared to controls DM, high TC, LDL, and low HDL were statistically more frequent in SCI patients. We found a negative correlation between serum HDL and time since injury. TC (186+/-32 vs 205+/-36; P=0.025), TC/HDL (5.34+/-1.17 vs 6.26+/-1.5; P=0.005), and LDL/HDL (3.57+/-0.9 vs 4.16+/-1.3; P=0.027) were significantly increased in patients with time since injury of more than 1 year, while HDL levels (35.8+/-6.36 vs 33.86+/-6.47; P=0.213) decreased without reaching statistical significance. The lipid profiles did not show any correlation with the neurological level, and completeness of lesions. CONCLUSIONS: SCI confers additional CHD risk over that present inherently in the parent population due to enforced sedentary lifestyle and this increases with time since injury. The preliminary study consisting of 26 patients was accepted for poster presentation in Copenhagen, Denmark (18-20 June 1999) at the 38th Annual Scientific Meeting of IMSOP in association with the Nordic Medical Society of Paraplegia.

Multiple vascular leiomyomas involving bilateral adrenal glands, spleen, and epicardium, associated with bilateral testicular microlithiasis and empty sella turcica.

Leiomyomas can arise from any tissue having smooth muscle as one of its constituents, especially gastrointestinal and genitourinary systems, less frequently in the skin, and rarely in deep soft tissue. An unusual case of multiple vascular leiomyomas involving bilateral adrenal glands, spleen, and epicardium, associated with bilateral testicular microlithiasis, and empty sella turcica is reported in a 15-year-old boy. The adrenal masses were incidentally discovered by ultrasonography. These three findings, taken individually are rare, and the constellation of the three, to the best of our knowledge, is the first recorded example. Furthermore, bilateral involvement of the adrenal glands with leiomyomas is, by itself, very uncommon. The tumors considered benign were surgically removed. Orchiectomy wasn't performed. The boy is well after 1.5-year follow-up under cortisone, 9alpha-fludrocortisone, and testosterone therapy.