Lack of association between endothelial nitric oxide synthase gene polymorphisms and risk of premature coronary artery disease in the Greek population.

OBJECTIVE: Genetic polymorphisms in the gene for endothelial nitric oxide synthase have been considered as potential risk factors for the development of coronary artery disease in some populations. METHODS: We studied two polymorphisms of the NOS3 gene, the VNTR in intron 4 (4VNTR) and the Glu298Asp polymorphism in exon 7, in relation to the existence of premature coronary artery disease and the occurrence of myocardial infarction.A total number of 370 individuals of the Greek population was examined by PCR-RFLP method.The patient group consisted of 209 subjects, aged less than 58 years presenting symptomatic coronary artery disease, documented by coronary angiography. RESULTS: The frequencies for bb, ab and aa genotypes of 4VNTR polymorphism were 0.67, 0.29, 0.04, respectively, for the patient group and 0.73, 0.24, 0.03 for the control group.The frequencies for GG (Glu/Glu), GT (Glu/Asp),TT (Asp/Asp) of the Glu298Asp polymorphism were 0.52, 0.41, 0.07, respectively, in patients compared to 0.47, 0.46, 0.07, in control subjects. Statistical analysis indicated that there are no significant differences in the frequencies of the genotypes between patients and control subjects for both polymorphisms. The combined analysis of the two polymorphisms indicated no synergistic effect of the a and T alleles on coronary artery disease. CONCLUSIONS: We have found no evidence for association between the a allele of the 4VNTR polymorphism, or the T allele of Glu298Asp polymorphism and the risk for premature coronary artery disease or occurrence of myocardial infarction. Furthermore, no synergistic contribution of these polymorphisms to the development of premature coronary artery disease has been observed.

White coat hypertension and haemostatic/fibrinolytic balance disorders.

White coat hypertension (WCH) or isolated clinic hypertension is generally accepted to be a benign condition, although some reports have suggested that it may be associated with an increased cardiovascular event rate or other cardiovascular alterations. It has been previously shown that essential hypertension (EH) is associated with abnormalities in haemostatic/fibrinolytic balance and endothelial function. The aim of our study was to assess the impact of WCH on fibrinolytic balance and endothelial function by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (tPA), fibrinogen, and thrombomodulin. These markers were determined in 71 patients with EH, 26 with WCH and 87 normotensive healthy control subjects. The three groups were not different with respect to age, gender, smoking habits, BMI and blood lipids. Subjects with WCH were found to have increased plasma levels of PAI-1, tPA, fibrinogen and thrombomodulin compared to controls, but less compared to hypertensive ones. Our results suggest that WCH may be associated with decreased fibrinolytic potential and endothelial dysfunction, indicating that WCH may not be a completely harmless trait.

Human soluble leptin receptor number in healthy normotensive individuals with high normal blood pressure.

BACKGROUND: High normal blood pressure (BP) seems to be related to increased cardiovascular risk in healthy normotensive subjects, whereas hyperleptinemia enhances both sympathetic tone and arterial BP. The aim of our study was to determine the human soluble leptin receptor number in healthy normotensive subjects with high normal BP and to compare these findings to those of healthy normotensive individuals with normal BP levels. METHODS: We studied 36 healthy normotensive individuals with high normal BP (19 men and 17 women, mean age 42+/-8 years, body mass index [BMI] 23+/-1.5 kg/m2) and 40 healthy normotensive individuals with normal BP (23 men and 17 women, mean age 43+/-7 years, BMI 23.2+/-1.4 kg/m2). The two groups are matched for age, sex, and BMI. The human soluble leptin receptor number and immunoreactive leptin levels were determined in the study population by enzyme-linked immunoassay and radioimmunoassay, respectively. RESULTS: Mean plasma leptin levels were significantly higher, whereas mean human soluble leptin receptor numbers were lower in the group with high normal BP compared with the normotensive group (10+/-4.8 v 6+/-2.7 ng/mL, P<.001 and 18+/-7 v 27+/-9 IU/mL, P<.001, respectively). CONCLUSIONS: Our findings indicate that normotensive individuals with high normal BP have statistically significantly higher plasma leptin levels and lower numbers of human soluble leptin receptors. This observation may play a important role in the pathogenesis of cardiovascular events in this special group of patients and needs further investigation.

Changes in metalloproteinases in healthy normotensive patients with high-normal blood pressure.

INTRODUCTION: High-normal blood pressure (HNBP) seems to be related to increased cardiovascular risk in healthy, normotensive subjects, while essential hypertension is associated with an increase in extracellular matrix content, especially fibrillar collagen type I. The aim of our study was to investigate whether collagen degradation is altered in healthy normotensives with HNBP, and whether this alteration could be related to disturbances in the matrix metalloproteinases plasma concentration, and to compare the findings to those of healthy normotensives with normal blood pressure (NBP) levels, matched for age, sex and BMI. METHODS: Twenty six (14 males, 12 females) healthy, normotensive patients with HNBP, mean age 52 +/- 5 yrs, and BMI 23 +/- 1.5 kg/m(2) (group A), and 24, healthy normotensive patients (13 males, 11 females) with NBP, mean age 53 +/- 6 yrs, and BMI 23.2 +/- 1.4 kg/m(2) (group B), were studied. The two groups were matched for age, sex and BMI. Plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors (TIMP-1) and (TIMP-4) were determined by relevant ELISA in the study population. RESULTS: Plasma MMP-9 levels were significantly higher, while TIMP-1 and TIMP-4 levels were significantly lower in group A compared to group B, (MMP-9 579 +/- 147 versus 294 +/- 111 ng/mL, TIMP-1 178 +/- 45 versus 237 +/- 35 ng/mL p < 0.01, and TIMP-4 2.2 +/- 1.4 versus 4.4 +/- 2.1 p < 0.04 respectively). CONCLUSIONS: Our findings suggest that healthy normotensives with high-normal blood pressure have significantly increased MMP-9 and decreased TIMP-1 and TIMP-4 plasma levels compared to healthy normotensives with normal blood pressure. These findings need further investigation.

Second recurrence of cardiac myxoma in a young patient. A case report.

Two cardiac myxomas, one in the right ventricle and another one in the right atrium causing pulmonary embolism, was removed in a 21-year-old male. In this patient, we visualized two more recurrences 6 and 11 years later one in the left atrium and the other in the left and right atrium.

Adiponectin and resistin plasma levels in healthy individuals with prehypertension.

Prehypertension seems to be related to increased cardiovascular risk in healthy subjects, while hypoadiponectinemia and hyperresistinemia may contribute to insulin resistance and accelerated atherogenesis. This study investigated whether plasma levels of adiponectin (known to increase insulin sensitivity) and resistin (a protein possibly involved in inflammatory activities) are affected in healthy individuals with prehypertension, and to compare the findings to those of healthy normotensives matched for age, gender, and body mass index. Twenty-six (14 men and 12 women) healthy individuals with prehypertension (mean age, 52+/-5 years; mean body mass index, 23+/-1.5 kg/m2) and 24 healthy normotensives (13 men and 11 women; mean age 53+/-6 years; body mass index 23.2+/-1.4 kg/m2) were studied. The adiponectin and resistin plasma levels were determined by the enzyme-linked immunosorbent assay method. Plasma resistin levels were significantly higher, while adiponectin plasma levels were significantly lower, in prehypertensive subjects compared with normotensive subjects (10.62+/-3.17 ng/mL vs. 6.72+/-3.15 ng/mL and 6.26+/-2.18 mg/mL vs. 12.12+/-4.8 mg/mL; p < 0.01, respectively). The findings suggest that healthy individuals with prehypertension have significantly higher resistin plasma levels and significantly lower adiponectin plasma levels compared with healthy normotensives. These findings may represent another possible mechanism that may increase the cardiovascular risk in this special group of patients, needing further investigation.

Apolipoprotein E genotype in dyslipidemic patients and response of blood lipids and inflammatory markers to alpha-linolenic Acid.

The objective of this study was to determine the effect of alpha-linolenic acid (ALA) supplementation on blood lipids and inflammatory markers, in relation to apolipoprotein (apo) E genotype. The diets of 50 dyslipidemic male patients were supplemented with 15 mL of flaxseed oil per day for 12 weeks. Retrospectively, 3 apo E genotype variants were found (epsilon2/epsilon3, n=7; epsilon3/epsilon3, n=33; epsilon3/epsilon4, n=10). No significant differences were found among apo E genotypes in any variables at baseline. ALA supplementation produced a small but significant decrease in high-density lipoprotein cholesterol (from 1.12 to 1.08 mmol/L, 43 to 42 mg/dL; p=0.008) and apo A-I levels (from 1.28 to 1.24 g/L, p=0.036) in the epsilon3/epsilon3 homozygotes. In addition, ALA supplementation resulted in a significant decrease in the serum concentration of serum amyloid A (SAA) (p=0.014), C-reactive protein (CRP) (p=0.013), macrophage colony-stimulating factor (MCSF) (p<0.001), and interleukin (IL)-6 (p=0.028). Serum SAA and MCSF were also significantly decreased in the epsilon3/epsilon4 group (p=0.005 and p=0.017, respectively). In contrast, ALA produced no effects on any of the inflammatory markers in the epsilon2/epsilon3 group. ALA may have beneficial effects on inflammation in dyslipidemic carriers of the apo epsilon3/epsilon3 and epsilon3/epsilon4 genotypes, but not in carriers of the epsilon2 allele.

Insulin receptor number is reduced in healthy offspring of patients with essential hypertension.

BACKGROUND: Epidemiologic studies have shown that healthy offspring of hypertensive patients exhibit many features of the metabolic syndrome, such as hyperinsulinemia, insulin resistance, and lipid disorders. Patients with essential hypertension have reduced numbers of insulin receptors. The aim of this study was to examine whether the number of insulin receptors is reduced in the erythrocytes of healthy offspring of hypertensive patients in comparison to the offspring of healthy normotensive subjects. METHODS: The study population consisted of 25 healthy offspring of patients with essential hypertension (group A) and 28 healthy offspring of healthy normotensive individuals (group B). The two groups were matched for sex, age, and body mass index. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), resting heart rate (HR), plasma insulin levels, and human insulin receptor (hINR) number in erythrocytes were determined in each participant. RESULTS: Mean SBP, DBP, and resting HR were significantly higher in group A than in group B (121 +/- 13 v 110 +/- 10 mm Hg, 78 +/- 6 v 73 +/- 8 mm Hg, and 76 +/- 4 v 72 +/- 6 beats/min; P < .01, P < .05, and P < .01, respectively). Plasma insulin levels were significantly higher, whereas hINR density was significantly lower, in group A than in group B (21 +/- 7 v 15 +/- 6 pIU/mL, P < .01, and 5.6 +/- 1.4 v 6.8 +/- 1.3 receptors x 10(3)/red cell, P < .01, respectively). CONCLUSIONS: Our findings suggest that increased SBP, DBP, HR, plasma insulin levels, and decreased erythrocyte hINR density preexist in healthy offspring of patients with essential hypertension.

Coexistence of atherosclerosis and fistula as a cause of angina pectoris: a case report.

INTRODUCTION: Coronary artery fistulas are abnormal communications between a coronary artery and a cardiac chamber or a major vessel (vena cava, pulmonary vein, pulmonary artery). They are usually diagnosed by coronary arteriography. Clinical presentations are variable depending on the type of fistula, shunt volume, site of the shunt, and presence of other cardiac conditions. CASE PRESENTATION: This report describes a 46-year-old Greek female patient who was admitted to the hospital because of an acute coronary syndrome. She underwent coronary angiogram which showed a coronary artery fistula from the left anterior descending artery to the main pulmonary artery and severe coronary disease. The patient was referred for coronary artery bypass surgery and fistula closure operation. CONCLUSIONS: Coronary artery fistulas between left anterior descending artery and main pulmonary artery are very rare anomalies. This case report describes a patient with this anomaly combined with severe coronary disease, reviews the current literature and discusses the available options for treating this rare condition.

Thoracic fluid content and impedance cardiography: a novel and promising noninvasive method for assessing the hemodynamic effects of diuretics in hypertensive patients.

INTRODUCTION: Impedance cardiography (ICG) is a reliable, noninvasive method allowing the assessment of the hemodynamic profile in hypertensive patients. The aim of the study was to evaluate the potential hemodynamic effects of diuretics with ICG and examine whether the empiric administration of diuretics actually has a substantial impact on thoracic fluid content (TFC). METHODS: The study population included 248 hypertensive and 68 healthy subjects (35-87 years old) and was divided into 4 groups: group A comprised hypertensive patients under treatment including diuretic; group B consisted of hypertensive patients under treatment without diuretic; group C included untreated hypertensive patients; and group D included healthy subjects. The measurements were performed using the Cardio Screen ICG system (Medis, Germany). Men and women were examined separately, since TFC seems to be sex-dependent. RESULTS: In the men's subgroup, the highest TFC value (41.7 +/- 4.9) was found in Group C (untreated hypertensive group), while the lowest TFC (36.4 +/- 5.7) was seen in Group A (diuretic hypertensive group). Women treated empirically with diuretics (group A) had a mean TFC of 27.3, while the other no-diuretic groups had a mean TFC of approximately 30. The mean TFC in men was significantly higher than in women in all study groups examined. CONCLUSIONS: Both men and women who were treated empirically with diuretics showed a significantly lower TFC in comparison with patients treated with other antihypertensive drugs, untreated patients and healthy control subjects. TFC is an ICG parameter that is associated with the administration of diuretics and has interesting clinical applications in optimizing and tailoring antihypertensive treatment.

Effects of flaxseed oil supplementation on plasma adiponectin levels in dyslipidemic men.

BACKGROUND: Dietary alpha-linolenic acid (ALA) has been associated with reduced risk of development of atherosclerosis. Adiponectin is a hormone specifically secreted by adipocytes and considered to have anti-atherogenic properties. AIM OF THE STUDY: We examined the effect of increased dietary intake of ALA on plasma concentration of adiponectin. METHODS: Thirty-five non-diabetic, dyslipidemic men, 38-71 years old, were randomly allocated to take either 15 ml of flaxseed oil rich in ALA (8.1 g/day; n = 18), or 15 ml of safflower oil per day, containing the equivalent n-6 fatty acid (11.2 g/day linoleic acid, LA; n = 17) (control group). The intervention period lasted for 12 weeks. RESULTS: Plasma levels of adiponectin did not change after the increase in dietary intake of ALA in the flaxseed oil supplementation group, compared to the control group. No changes in body mass index, serum lipid concentrations, LDL density, or plasma TNF-alpha were found in the flaxseed oil versus the control group. CONCLUSIONS: Dietary ALA has no effect on plasma adiponectin concentration in dyslipidemic men.

Role of perindopril in the prevention of stroke.

Stroke is one of the leading causes of disability and death worldwide and is a more common cause of cardiovascular morbidity and mortality than myocardial infarction among patients with hypertension. Identifying and modifying key risk factors is crucial to reduce morbidity and mortality from stroke. Hypertension is the most important modifiable risk factor for ischemic stroke, and antihypertensive treatment is of paramount importance to reduce the incidence of stroke mortality and morbidity. Perindopril is a third-generation long acting, once-daily lipophilic angiotensin-converting enzyme inhibitor with high tissue angiotensin-converting enzyme affinity, lowering angiotensin II and potentiating bradykinin. Its efficacy, safety and tolerability are well established in the treatment of hypertension and heart failure. The purpose of this article is to review the evidence from clinical trials as well as from recent patents that has been gathered in regard to perindopril, demonstrating not only its efficacy in reducing blood pressure, but also to other cardiovascular protective properties that act in addition to the obvious blood-pressure-lowering effect in the prevention of stroke in patients with essential hypertension, with particular attention paid to the results from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).

Background diet influences the anti-inflammatory effect of alpha-linolenic acid in dyslipidaemic subjects.

Long-chain n-3 PUFA from fish oils are known to have anti-inflammatory effects. We evaluated the effect of alpha-linolenic acid (ALA), precursor of n-3 fatty acids, on serum inflammatory markers and soluble cellular adhesion molecules (sCAM) of dyslipidaemic males, relative to their background diet. Participants were assigned to two groups, based upon food intake patterns: (a) twenty-one dyslipidaemic subjects who habitually ate a Mediterranean-Cretan-type diet; (b) nineteen dyslipidaemic subjects who normally ate a Westernised Greek diet. All were supplemented with 8.1 g ALA/d for 12 weeks. We determined serum amyloid A (SAA), C-reactive protein (CRP), macrophage colony-stimulating factor (MCSF), IL-6, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 and soluble E-selectin concentrations at the beginning and the end of the ALA supplementation period. Serum baseline concentrations of inflammatory markers and sCAM were similar across the diet groups. Type of diet had a significant impact on the response of inflammatory markers to ALA supplementation. The Westernised Greek diet group showed a reduction in SAA (P<0.001), CRP (P=0.002), MCSF (P=0.005) and IL-6 (P=0.04) concentrations. The Mediterranean-Cretan-type background diet group showed a significant reduction only in MCSF concentrations (P=0.003). The sVCAM-1 concentrations were significantly reduced in both the Westernised Greek diet group (P=0.001) and the Mediterranean-Cretan-type diet group (P<0.001). The present study demonstrated that ALA supplementation lowered the serum concentrations of inflammatory markers more profoundly when the background diet was rich in saturated fatty acids and poor in MUFA.