Association of plasma dehydroepiandrosterone-sulfate levels with endothelial function in postmenopausal women with coronary risk factors.

Age-related decline of plasma dehydroepiandrosterone-sulfate (DHEA-S) levels may be associated with the risk of cardiovascular disease in women. We investigated whether plasma DHEA-S levels are related to endothelial function in postmenopausal women with coronary risk factors. One hundred and fifteen postmenopausal women (mean age+/-SD: 57+/-5 years; range: 48-65 years) who underwent measurement of flow-mediated vasodilation (FMD) of the brachial artery using ultrasonography were enrolled. Plasma hormone levels were determined in the morning after a 14-h fast, and the relationship between hormone levels and FMD was analyzed. DHEA-S was significantly correlated with %FMD (r=0.392, p<0.001), while estradiol, total testosterone and cortisol were not. %FMD in the highest quartile of DHEA-S was 1.8-fold higher than that in the lowest quartile (5.3+/-1.3 vs. 2.9+/-2.0 [means+/-SD], p<0.01). Multiple regression analysis revealed that DHEA-S was related to %FMD independent of age, body mass index, hypertension, hyperlipidemia, diabetes mellitus and smoking (beta=0.344, p<0.01), and was itself independent of age, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting plasma glucose and smoking (beta=0.291, p<0.05). In conclusion, plasma DHEA-S levels were weakly but significantly related to endothelial function in postmenopausal women independent of other coronary risk factors, suggesting a protective effect of DHEA on the endothelium.     

Improvement of endothelial dysfunction in acromegaly after transsphenoidal surgery

Flow-mediated vasodilatation (FMD) is a vascular functional test to detect endothelial dysfunction at the early stage of cardiovascular diseases. Patients with active acromegaly have higher morbidity and mortality due to cardiovascular events. To determine whether active acromegaly is associated with endothelial dysfunction, we studied 17 patients with active acromegaly for measurements of FMD, carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV), and other biochemical parameters before and 3 months after transsphenoidal surgery (TSS). Baseline %FMD in patients with active acromegaly was significantly lower than that in age- and sex-matched control subjects. After TSS, the mean %FMD in acromegaly significantly increased from 5.3% to 7.4%; 12 patients had increased %FMD (responders), whereas 5 patients had decreased or unchanged %FMD (non-responders). However, neither carotid IMT nor baPWV changed after TSS. Serum levels of GH, insulin-like growth factor (IGF)-1, total cholesterol, low-density lipoprotein cholesterol (LDL-C), hemoglobin HA(1C), fasting plasma glucose and insulin levels, and homeostasis model assessment (HOMA)-R significantly decreased, whereas high-density lipoprotein cholesterol significantly increased. Responders had significantly lower baseline %FMD than did non-responders and both insulin levels and HOMA-R significantly decreased in responders, but not in non-responders after TSS. Simple regression analysis revealed that the change of %FMD showed a significant negative correlation with that of LDL-C, but not of IGF-1 or GH, in responders. In conclusion, it is suggested that endothelial dysfunction associated with active acromegaly improves soon after TSS, which is related to LDL-C and/or insulin resistance, but not to excess GH and/or IGF-1 itself.     

Relationship between endothelial function and coronary risk factors in patients with stable coronary artery disease.

BACKGROUND: Results of experimental and clinical studies suggest that both coronary artery disease (CAD) itself and its traditional risk factors lead to endothelial dysfunction. The aim of the present study was to determine which CAD risk factors sustain their contribution to endothelial dysfunction despite the presence of established CAD. METHODS AND RESULTS: The study group comprised 150 patients with CAD. Using a high-resolution ultrasound, the diameter of the brachial artery at rest and during reactive hyperemia (flow-mediated dilatation, FMD%: endothelial-dependent stimulus to vasodilatation), as well as after sublingual administration of nitroglycerin (NTG%: endothelium-independent vasodilatation), was measured. The relationship between FMD% and coronary risk factors [diabetes mellitus (DM), total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, age, family history of premature atherosclerosis, smoking, hypertension (HT), body mass index (BMI)] was investigated. In univariate analysis there was an inverse relationship between FMD% and age (r=-0.300, p<0.001), and BMI (r=-0.230, p<0.005) and FMD% was significantly lower in diabetic patients when compared to non-diabetic patients (p<0.001). In stepwise multivariate regression analysis; FMD still correlated with DM and advanced age, but not with BMI (beta=0.065, p<0.001, beta=-0.001 p=0.002, beta=-0.087, p<0.284, respectively). FMD% was found to be not associated with hypercholesterolemia, family history of premature atherosclerosis, HT and smoking. CONCLUSION: Only aging and DM were independently associated with endothelial dysfunction in patients with established CAD.     

Soluble vascular endothelial growth factor, soluble VEGF receptor Flt-1 and endothelial function in healthy smokers

OBJECTIVE: To relate levels of vascular endothelial growth factor (VEGF) and its soluble receptor, sFlt-1, with endothelial function in healthy smokers. METHODS: Plasma levels of VEGF and sFlt-1 were measured by ELISA in 22 healthy smokers and 22 matched healthy non-smoking controls, and compared to flow- (FMD) and acetylcholine-mediated (AMD) vasodilatation (endothelial-dependent) (EDV) and nitroglycerine-mediated (NMD) vasodilatation (endothelial-independent) of lower extremities were measured with plethysmography. RESULTS: Smokers and controls had similar plasma VEGF levels, but sFlt-1 levels were lower in smokers than in controls (p<0.01). AMD was lower in smokers compared to controls (p<0.05), but FMD and NMD levels were similar. Smokers and controls with high AMD (>12 ml/100 ml tissue/min) had significantly lower plasma VEGF levels (p<0.001). An inverse correlation was found in both groups, between VEGF and AMD (smokers: r=-0.6, p<0.01; controls: r=-0.71, p<0.005) and with FMD (smokers: r=-0.56, p<0.05; controls: r=-0.58, p<0.005). There were no significant correlations between sFlt-1 with VEGF levels or endothelial-dependent dilatation. CONCLUSION: In conclusion, healthy smokers demonstrate abnormal AMD, and an inverse correlation between plasma VEGF levels (but not sFlt-1) with indices of endothelial dysfunction (FMD and AMD) exists. VEGF, and not sFlt-1, may be related to the pathogenesis of endothelial dysfunction in healthy smoking individuals.     

Amelioration of vascular endothelial dysfunction in obstructive sleep apnea syndrome by nasal continuous positive airway pressure--possible involvement of nitric oxide and asymmetric NG, NG-dimethylarginine.

BACKGROUND: Asymmetric NG,NG-dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase and its plasma concentration is elevated in patients with cardiovascular risk factors, including hyperlipidemia, hypertension, diabetes, and hyperhomocysteinemia. Obstructive sleep apnea syndrome (OSAS) has been attracting attention as a risk factor for cardiovascular disorders because it often accompanies hypertension, obesity, glucose impairment, and dyslipidemia, all of which are factors in metabolic syndrome and risk factors for cardiovascular disease. METHODS AND RESULTS: In the present study, flow-mediated vasodilatation (FMD) of the brachial artery and plasma concentrations of ADMA were measured before and after nasal continuous positive airway pressure (nCPAP) therapy, which abrogates apnea, in 10 male patients aged 36-69 years old, who were given a diagnosis of OSAS by polysomnography. The percent FMD (%FMD) improved significantly from 3.3+/-0.3% to 5.8+/-0.4% (p<0.01) and 6.6+/-0.3% (p<0.01), before, 1 week, and 4 weeks after nCPAP, respectively. At the same time, the plasma NOx concentrations, metabolites of NO, tended to increase, but the plasma ADMA concentration decreased inversely to %FMD and NOx. A negative correlation between %FMD and plasma ADMA concentration, and a positive correlation between %FMD and plasma NOx concentrations were observed. CONCLUSION: Nasal CPAP improves endothelial function, in part by the decreasing ADMA concentration, thereby potentiating NO production.     

Contribution of age and declining androgen levels to features of the metabolic syndrome in men

Plasma dehydroepiandrosterone sulfate (DHEA-S) and testosterone levels both decline with age in healthy men. Features of the metabolic syndrome also show age-related deteriorations. We examined the relative contribution of age and declining androgen levels to features of the metabolic syndrome in men. In a sample of 130 nonsmoking men from the Quebec Family Study, we tested the hypothesis that age-related decreases in DHEA-S and testosterone levels would explain most of the variance in alterations of the metabolic profile associated with aging. As expected, we found that plasma DHEA-S and testosterone levels were negatively associated with age. Significant negative correlations were found between androgen levels and adiposity measures, body fat distribution, and metabolic risk variables. Statistical control for age eliminated correlations with DHEA-S, whereas age-adjusted associations between testosterone and most adiposity and metabolic variables remained significant. The percentage frequency of men characterized by 3 or more features of the metabolic syndrome increased with decreasing testosterone (8.9%-44.2%, chi2 = 15.89, P < .0005 ) and DHEA-S levels (8.9%-41.5%, chi2 = 13.02, P < .005). Logistic regression analyses showed that men in the upper tertile of testosterone levels had a lower risk of being characterized by 3 or more features of the metabolic syndrome (odds ratio = 0.24, P < .04) independent of age, whereas tertiles of DHEA-S levels were not related to the metabolic syndrome independent of age. In conclusion, results suggest that age per se is an important correlate of the associations between DHEA-S and metabolic variables, whereas the association of plasma testosterone levels to features of the metabolic syndrome appears to be independent of age.     

Cardiovascular risk factors in healthy women with previous gestational hypertension

CONTEXT: Epidemiological studies indicate that gestational hypertension (Gh) during pregnancy is associated with increased risk of cardiovascular disease in later life. However, it is unclear whether particular metabolic and hemodynamic characteristics are related to this risk. OBJECTIVE: The objective of this study was to investigate endothelial function and carbohydrate and lipid metabolism in healthy, normotensive women with previous pregnancy complicated by Gh. DESIGN, SETTING, AND PARTICIPANTS: Brachial artery flow-mediated dilatation (FMD; endothelium dependent) and nitroglycerin-induced dilatation (endothelium independent) were measured in 15 subjects with previous Gh and in 15 controls with previous normal pregnancies. Lipid panel, glucose, insulin, homocysteine, and androgens were also measured. RESULTS: FMD was significantly reduced in women with previous Gh compared with controls (P < 0.0001), whereas nitroglycerin-induced dilatation was comparable in both groups. Gh women showed increased fasting insulin (P = 0.011), insulin resistance measured by homeostasis model assessment (P = 0.018), free fatty acids (P = 0.0018), and testosterone (P = 0.0012) and decreased high-density lipoprotein cholesterol (P = 0.0017) compared with controls. Across all subjects, FMD showed a strong independent negative correlation with testosterone and homeostasis model assessment and a positive correlation with high-density lipoprotein cholesterol (r = -0.60, P = 0.0003; r = -0.43, P = 0.016; and r = 0.58, P = 0.0005, respectively). CONCLUSIONS: Endothelial dysfunction and early alteration of carbohydrate and lipid metabolism are present in otherwise healthy women with previous Gh. These abnormalities along with a relative hyperandrogenism could explain, at least in part, the increased risk for cardiovascular disease in later life in these women.     

Effects of chronic cigarette smoking on endothelial function in young men

The aim of this study was to elucidate endothelial dysfunction due to chronic cigarette smoking in young smokers and to determine practical markers of the functional derangement. The subjects were young, healthy, male non-smokers (n=11) and smokers (n=9). Endothelium-dependent and -independent vasodilation was assessed by flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID), respectively, and possible markers of endothelial function were measured. FMD in smokers was significantly lower than in control subjects (5.0 ± 2.6% and 9.5 ± 5.2%, p<0.05). Plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator levels were significantly (p<0.05) higher in smokers (6.7 ± 4.5 ng/ml and 4.3 ± 2.0 ng/ml) compared with control subjects (2.9 ± 1.9 ng/ml and 3.0 ± 0.6 ng/ml). Furthermore, PAI-1 levels correlated inversely with FMD (r=-0.451, p<0.05). No significant differences were observed for NID, or plasma NO(2)(-), NO(X), thrombomodulin, von Willebrand factor, and tissue factor pathway inhibitor levels. Chronic cigarette smoking-induced endothelial dysfunction and the PAI-1 level could be a good marker of endothelial dysfunction in young smokers.     

Relationship between Endothelial Dysfunction and Prevalence of Chronic Kidney Disease: The Circulatory Risk in Communities Study (CIRCS)

Aims: Patients with chronic kidney disease (CKD) have a higher burden of cardiovascular morbidity and mortality than the general population. Endothelial dysfunction has been suggested to play a role in both glomerular filtration rate loss and cardiovascular damage. Thus, the present study aimed to evaluate the relationship between endothelial dysfunction and the prevalence of CKD in the general Japanese population. Methods: We conducted a cross-sectional study of 1042 men and women aged 30–81 years in two communities under the Circulatory Risk in Communities Study between 2013 and 2017. Endothelial function was evaluated by percent change of brachial artery flow-mediated dilation (%FMD) before and after the cuff inflation. Results: Among the total 1042 participants, there were 62 cases of CKD (~6%). The multivariable odds ratios (ORs) (95% confidence intervals [CIs]) of CKD according to quartiles of %FMD were 2.02 (0.68–5.99), 3.56 (1.27–9.94), and 3.14 (1.10–8.93) for the third to lowest quartile compared with the highest %FMD quartile; p for trend=0.02. The respective multivariable ORs (95% CIs) of CKD in subjects without antihypertensive medication use (39 cases among 886 subjects) were 1.83 (0.46–7.33), 3.41 (0.92–12.61), and 4.60 (1.22–17.31); p for trend=0.01, and that for one-point decrement in %FMD was 1.16 (1.00–1.35); p for interaction with the status of antihypertensive medication use was 0.12. Conclusions: Our cross-sectional study suggested the relationship between endothelial dysfunction and the higher prevalence of CKD in the general Japanese population.     

Pregnancy-related hyperlipidemia and endothelial function in healthy women.

BACKGROUND: The purpose of the present study was to investigate pregnancy-related changes in the maternal serum lipid profile and endothelial function. METHODS AND RESULTS: As part of the population-based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland, 57 pregnant Finnish women and 62 control women matched for age and smoking were examined throughout gestation. Serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined and concomitantly endothelium-dependent brachial artery flow mediated dilation (FMD) was measured by ultrasound. During pregnancy serum TC, LDL-C, HDL-C, TG and very-low-density lipoprotein cholesterol increased significantly when compared with the non-pregnant state (p<0.001 for each) and towards the end of pregnancy (p<0.001, p<0.001, p=0.007, p<0.001, p<0.001). FMD increased towards the end of pregnancy and there was a statistically significant direct correlation between gestational age and FMD% (r=0.345, p=0.010). Brachial artery diameter at rest and FMD% were negatively correlated in pregnant (r=-0.280, p=0.035) and non-pregnant women (r=-0.360, p<0.004). The univariate correlation analysis showed a direct correlation between maternal serum TC (r=0.333, p=0.012) and TG (r=0.366, p=0.006) and FMD%, whereas a negative non-significant correlation was found in non-pregnant women. In a multivariate model, vessel size (beta=-0.436, p=0.001) and TG (beta=0.502, p<0.001) were the most powerful predictors for FMD% in pregnancy, the influence of other lipids was non-significant. CONCLUSIONS: In healthy pregnant women increased gestational age is associated with improved endothelium-dependent vasodilation responses regardless of concurrently appearing lipid changes.     

Racial (black-white) comparisons of the relationship of levels of endogenous sex hormones to serum lipoproteins during male adolescence: the Bogalusa Heart Study

The cross-sectional relationship of endogenous androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate [DHEA-S]), estrogen (estradiol) and progestin (progesterone) to serum levels of lipoprotein cholesterol (very low-density [VLDL], low-density [LDL], and high-density lipoprotein [HDL]) and apolipoproteins (apo A-I and apo B) were studied in white (n = 251) and black (n = 258) adolescent boys, ages 11 to 17 years, as part of the Bogalusa Heart Study. Black boys had significantly higher levels of estradiol, HDL cholesterol, and apo A-I, and lower levels of androstenedione and VLDL cholesterol than white boys, independent of age and adiposity. Age was correlated strongly with testosterone and androstenedione, and moderately with DHEA-S and estradiol levels in both races. However, only in white boys was age consistently related to VLDL cholesterol (positively), HDL cholesterol (negatively), and apo A-I (negatively). Overall, testosterone was associated inversely with HDL cholesterol and apo A-I in white boys, while progesterone was related positively to apo A-I in both races after adjusting for age and adiposity. However, these relationships were found to differ with age. Partial correlations between levels of sex hormones and lipoproteins adjusted for age and adiposity showed no associations in the 11 to 12 year age group in boys of either race. A significant positive relation of testosterone to VLDL cholesterol, and inverse relations of testosterone to HDL cholesterol and apo A-I and DHEA-S to HDL cholesterol were apparent only in white boys in the 13 to 14 year age group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brachial artery endothelial function predicts platelet function in control subjects and in patients with acute myocardial infarction

Platelet activation occurs in an endothelium-dependent flow-mediated dilation (FMD) impairment environment. The aim of this study was to explore the association between platelet reactivity and brachial artery FMD in individuals without established cardiovascular disease (controls) and acute myocardial infarction (AMI) patients. We prospectively assessed brachial artery FMD in 151 consecutive subjects, 104 (69%) controls, and 47 (31%) AMI patients; 115 (76%) men, mean age 53?±?11 years. Following overnight fasting and discontinuation of all medications for?≥?12?h, percent change in brachial artery FMD (%FMD) and endothelium-independent, nitroglycerin-mediated vasodilation (%NTG) were assessed. Platelet aggregation was assessed by conventional aggregometry, and platelet adhesion and aggregation under flow conditions by cone-and-plate(let) technology (Impact-R). Smoking, diabetes, and hypertension were more common in AMI compared to control subjects (p?<?0.01 for all). Furthermore, aspirin, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors, and statin administration were more common in AMI compared to controls (p?<?0.01 for all). %FMD but not %NTG was significantly lower in AMI patients compared to controls (10.2?±?4.2% vs. 15.4?±?4.4%; p?<?0.001 and 17.2?±?3.9% vs. 18.0?±?3.7%, p?=?0.803, respectively). %FMD was significantly and inversely associated with all platelet functions tests (p?<?0.001) in all study participants. In a multivariate logistic regression (unadjusted and adjusted for age, gender, smoking status, diabetes mellitus, hypertension, hypercholesterolemia, overweight, family history, and concomitant medications), %FMD remained the best predictor of platelet function, irrespective of group allocation (AMI patients or controls). In conclusion, FMD is inversely correlated to platelet reactivity in both controls and AMI patients.     

Vascular endothelial and smooth muscle function relates to body mass index and glucose in obese and nonobese children

CONTEXT: Endothelial and smooth muscle dysfunction are critical precursors of atherosclerosis. These can be detected in children at risk of cardiovascular disease. OBJECTIVE: The objective of this study is to evaluate endothelial and smooth muscle function and their determinants using flow-mediated dilatation (FMD) and glyceryl trinitrate-mediated dilatation (GTN) in obese, nonobese, and type 1 diabetes mellitus (T1DM) children. DESIGN: This is a cross-sectional study. SUBJECTS: The study subjects were 270 children [140 males, mean age 13.7 (2.8) yr] including 58 obese, 53 nonobese, and 159 T1DM children. MEASUREMENTS: Vascular function (FMD and GTN), body mass index (BMI) z-score, blood pressure, glucose, glycosylated hemoglobin, lipids, folate, homocysteine, and high sensitive C-reactive protein were measured. RESULTS: FMD and GTN were significantly lower in obese and T1DM compared with nonobese subjects (P < 0.001, P < 0.001). FMD and GTN were similarly reduced in obese and T1DM subjects (P = 0.22, P = 0.28). In all nondiabetic subjects (n = 111), both FMD and GTN were significantly and independently related to BMI z-score (r = -0.28, P = 0.003, beta = -0.36, P < 0.001) and weight z-score (beta = -0.31, P = 0.002; r = -0.52, P < 0.001). FMD related independently to total cholesterol (beta = -0.22, P = 0.02). GTN related independently to vessel diameter (beta = -0.49, P < 0.001). GTN related to glucose within the normal range (r = -0.34, P = 0.001). CONCLUSIONS: Children with obesity and T1DM have a similar degree of vascular dysfunction. BMI and weight adjusted for age and sex relate to endothelial and smooth muscle function in nonobese and obese children. Glucose relates to smooth muscle function in nonobese nondiabetic children. This suggests a continuum effect of BMI and glucose within the normal range on vascular function in childhood.     

Close association of endothelial dysfunction with insulin resistance and carotid wall thickening in hypertension

BACKGROUND: Endothelial dysfunction has been regarded as an early stage in the atherosclerotic process. Endothelial dysfunction and insulin resistance were observed in hypertensive subjects and were associated with carotid wall thickening. METHODS: We examined the determinants of endothelial dysfunction including insulin sensitivity and carotid wall thickening. A total of 41 subjects with nondiabetic essential hypertension were studied. Endothelial function of brachial artery and carotid wall thickening were assessed noninvasively using ultrasound technique. In brachial artery, we measured flow-mediated endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced endothelium-independent vasodilation (GTN). We estimated intima-media thickness of the common carotid artery (IMT). Insulin sensitivity was measured according to the steady-state plasma glucose (SSPG) method. High SSPG levels indicated insulin resistance. RESULTS: On univariate analysis, there were significant negative correlations between FMD and SSPG (r = -0.695, P <.0001) or IMT (r = -0.449, P <.004). The FMD was negatively correlated significantly with age and with systolic and diastolic blood pressures (BP). A significant negative correlation was observed between GTN and SSPG. There was a significant positive relation between SSPG and IMT. On multiple regression analysis including systolic BP, SSPG, and age as independent variables and FMD as a dependent variable, FMD was independently related to SSPG (P <.03) and systolic BP (P <.02). If the presence of SSPG, diastolic BP, and age were entered as independent variables against FMD, FMD was independently related to SSPG (P <.002). CONCLUSIONS: One of the major determinants of endothelial function was insulin resistance. Our findings suggest that endothelial dysfunction and early structural vascular changes were related to insulin resistance.     

Inter-relationships of indices of endothelial damage/dysfunction [circulating endothelial cells, von Willebrand factor and flow-mediated dilatation] to tissue factor and interleukin-6 in acute coronary syndromes

BACKGROUND: Increased circulating endothelial cells (CECs, reflecting endothelial damage) in acute coronary syndromes (ACS) has been reported. However, the inter-relationships of indices of endothelial damage/injury with development of vascular (dys)function, plasma levels of tissue factor (TF, an index of coagulation) and interleukin-6 (IL-6, a pro-inflammatory cytokine) have not been investigated in ACS. We hypothesized that increased CECs can be related to impaired flow-mediated vasodilatation (FMD, an index of endothelial dysfunction) and elevated plasma von Willebrand factor (vWf, also marking endothelial damage/dysfunction), TF and IL-6 in patients with ACS. METHODS: We studied 120 patients with ACS (80 acute myocardial infarction and 40 unstable angina; 86 male, age 65+/-12 years) and 40 matched patients with stable CAD and 40 healthy controls (HC) in a cross-sectional analysis. Plasma vWf, TF and IL-6 levels were measured by ELISA. CECs were quantified using epifluorescence microscope after immunomagnetic separation with CD146. Brachial artery FMD was assessed in a subset of 39 ACS patients. RESULTS: ACS patients had significantly higher CECs, vWf, TF and IL-6 levels, but lower FMD, when compared to stable CAD and HC (all p<0.001) and all were inter-correlated significantly. In ACS, CECs was strongly correlated with FMD (r=-0.64, p<0.001) and TF (r=0.7, p<0.001). In stable CAD, significant correlations were again found between many indices, but on multivariate analysis, IL-6 and vWf were both independently related to FMD. CONCLUSIONS: Increased CECs in ACS patients are closely associated with endothelial damage/dysfunction (vWf and FMD), coagulation (TF) and inflammation (IL-6). These inter-relationships support the concept of a central role of endothelial damage/injury in the activation of vascular and coagulation abnormalities in ACS.     

Relationship between low serum endogenous androgen concentrations and arterial stiffness in men with type 2 diabetes mellitus

The aim of this study was to evaluate the relationship between arterial stiffness determined by pulse wave velocity (PWV) and serum endogenous androgen concentrations as well as major cardiovascular risk factors in men with type 2 diabetes mellitus. Serum free testosterone and dehydroepiandrosterone sulfate (DHEA-S) concentrations were measured in 268 men with type 2 diabetes mellitus. Relationships between PWV and serum endogenous androgen concentrations as well as major cardiovascular risk factors, including age, blood pressure, serum lipid concentration, glycemic control (hemoglobin A(1c)), body mass index, and degree of albuminuria, were evaluated. Positive correlations were found between PWV and age (r = 0.491, P < .0001), duration of diabetes (r = 0.320, P < .0001), systolic blood pressure (r = 0.292, P < .0001), and log (urinary albumin excretion) (r = 0.269, P < .0001). Inverse correlations were found between serum free testosterone concentration and PWV (r = -0.228, P = .0003) and between serum DHEA-S concentration and PWV (r = -0.252, P = .0002) in men with type 2 diabetes mellitus. Pulse wave velocity was significantly greater in patients with lower concentrations of free testosterone (<10 pg/mL) than in patients with higher concentrations of free testosterone (1864 +/- 359 vs 1736 +/- 327 cm/s; P = .0053). Pulse wave velocity also was significantly greater in patients with lower concentrations of DHEA-S (<1000 ng/mL) than in patients with higher concentrations of DHEA-S (1843 +/- 371 vs 1686 +/- 298 cm/s; P = .0008). Multiple regression analysis identified both serum free testosterone concentration (beta = -.151, P = .0150) and serum DHEA-S concentration (beta = -.200, P = .0017) as independent determinants of PWV. In conclusion, serum endogenous androgen concentrations are inversely associated with arterial stiffness determined by PWV in men with type 2 diabetes mellitus, which is true for men in general based on other works.     

Predictors of endothelial dysfunction in young women with polycystic ovary syndrome

CONTEXT: Women with polycystic ovary syndrome (PCOS) may be at increased risk for cardiovascular disease. Endothelial dysfunction is an early marker of atherosclerosis. OBJECTIVES: The objectives of this study were to 1) compare endothelial function in young women with PCOS and regularly menstruating control women, and 2) to identify the determinants of endothelial function and investigate its relationship with body mass index in women with PCOS. DESIGN: This was a cross-sectional study. SETTING: This study was conducted at a tertiary cardiovascular research center. PATIENTS: Sixty-two young women with PCOS (mean age, 22.7 yr) and 17 control women, matched as a group for age and body mass index, were studied. Twenty-three women with PCOS were lean, 21 were overweight, and 18 were obese. MAIN OUTCOME MEASURES: Endothelium-dependent and -independent vascular function was assessed by measuring flow-mediated dilation (FMD) and nitrate-mediated dilation in the brachial artery (diameter change during hand hyperemia and after sublingual glyceryl trinitrate administration, respectively). RESULTS: FMD and nitrate-mediated dilation were significantly lower in PCOS than in control women (reduced by approximately 50 and 25%, respectively; both P < 0.0005). Insulin resistance, total testosterone, and total cholesterol were independent predictors of FMD, accounting for 21, 10, and 9% of the variance, respectively (P < 0.005 for all). A trend of deterioration in FMD from lean to overweight and obese PCOS women was observed, but differences among groups were not statistically significant. CONCLUSIONS: Women with PCOS have significant endothelial dysfunction at an early age (i.e. early 20s), and largely independent of obesity. This suggests that women with PCOS are at increased risk for early onset cardiovascular disease and may gain particular benefit from measures to improve endothelial function.     

Relationship of high density lipoprotein cholesterol with total and free testosterone and sex hormone binding globulin

A cross-sectional study was performed to see if the previously described association between high density lipoprotein (HDL) cholesterol and plasma total testosterone concentration reflected a relationship with free testosterone or with sex hormone binding globulin (SHBG). In 295 employed middle-aged men, measurements were made of total testosterone and SHBG in serum and of testosterone in saliva, and also of plasma total and HDL cholesterol, plasma triglycerides and other factors which might influence HDL cholesterol levels such as body mass index, alcohol and smoking habits and thyroid hormone levels. In a multiple regression analysis using the GLIM package programme total testosterone concentrations had a persistent positive association with HDL cholesterol (t = 3.5, P less than 0.001) - this association was independent of SHBG (which had a negative association with HDL: t = -1.8, P less than 0.07. The association of HDL cholesterol with testosterone was independent of and stronger than the association of HDL cholesterol with body mass index, alcohol intake and cigarette smoking. Salivary testosterone (a measure of the circulating free hormone) also had a positive independent association with HDL cholesterol. The relationship between HDL cholesterol and testosterone thus appears to reflect an association with circulating hormone levels rather than with the hormone binding globulin.     

Endogenous estrogen levels are associated with endothelial function in males independently of lipid levels

Estrogens and androgens may play an important role in vascular health in both sexes. The aim of this study was to examine the relation of endogenous sex hormone levels with early markers of atherosclerosis in a cohort of apparently healthy males. 124 males (age 46.25 ± 9.56) attending a preventive medicine program were examined for unrecognised features of the metabolic syndrome. Flow-mediated dilatation (FMD) and intima-media thickness (IMT) of the common carotid artery were evaluated. Obesity parameters were recorded; estradiol, testosterone, SHBG, free testosterone, insulin, as well as glucose and lipid levels were measured. FMD was positively correlated with estradiol (r = 0.201, P = 0.041) and negatively with total cholesterol (r = -0.205, P = 0.022), low density lipoproteins (r = -0.232, P = 0.009), and triglyceride levels (r = -0.179, P = 0.046). In multivariate analysis, the association of FMD with estrogen was independent of BMI and lipid levels. No significant association between FMD and testosterone levels was found. Subjects with an increased mean IMT (> 0.73 mm, i.e., > 3rd tertile) had lower levels of free (P = 0.021) and bioavailable (P = 0.016) testosterone. In multivariate logistic regression analysis, this association was no longer significant when age or cholesterol levels were considered. Endogenous estrogen levels are associated with FMD, independently of age and lipid levels, showing a protective effect in middle-age male subjects. Circulating androgens are associated, although not independently, with structural changes such as the IMT of carotid artery; this effect is possibly influenced by lipid levels and age.     

Adrenal C19 steroids and serum lipoprotein levels in healthy men

BACKGROUND AND AIM: It has become apparent that dehydroepiandrosterone (DHEA) plays a protective role in atherosclerosis, but its influence on serum lipids has not yet been clarified. The aim of this study was to evaluate the association of endogenous adrenal C19 steroid hormones [(DHEA) and androstenedione (ASD)] and serum lipoprotein levels. METHODS AND RESULTS: The serum concentrations of dehydroepiandrosterone sulphate (DHEA-S), ASD, total and free testosterone, estradiol, total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides, apolipoprotein AI (ApoAI) and apolipoprotein B100 (ApoB100) were measured in a sample of 88 healthy men. Statistical analysis using Spearman's correlation coefficient showed a positive correlation between DHEA-S levels and ApoAI (p = 0.034), a negative correlation between ASD and triglycerides (p = 0.005), a positive correlation between ASD and LDL-C (p = 0.005), and a negative correlation between estradiol and HDL-C (p = 0.042). Multiple regression analysis revealed that DHEA-S is an independent factor for ApoAI, ASD an independent factor for triglycerides and LDL-C, and age an independent factor for ApoB100; estradiol was found to be a suggestive factor for HDL. CONCLUSIONS: The results suggest that the plasma levels of DHEA-S and ASD (adrenal C19 steroid hormones) correlate with the plasma lipid profiles of healthy men. It remains to be seen whether this profile is favourable.