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PubMed2004

Myocardial perfusion reserve and peripheral endothelial function in patients with idiopathic dilated cardiomyopathy.

The aim of this study was to assess the relation between peripheral endothelial function and myocardial perfusion reserve in patients with mild heart failure due to idiopathic dilated cardiomyopathy (IDC). Myocardial perfusion and brachial artery flow mediated dilation (FMD) were measured in 20 clinically stable patients with IDC (New York Heart Association classes I to III, ejection fraction 35 +/- 9%) and 13 apparently healthy subjects who were matched for age and lipid profile. Resting and hyperemic (dipyridamole; 0.56 mg/kg/min) perfusion were measured using oxygen-15-labeled water and positron emission tomography (PET). Perfusion reserve was calculated as the ratio of hyperemic to resting perfusion. FMD was assessed by measuring the change in brachial artery diameter in response to reactive hyperemia. Patients with IDC had lower hyperemic perfusion (1.73 +/- 0.83 vs 3.01 +/- 1.20 ml/min/g, p <0.001) and perfusion reserve (2.01 +/- 0.91 vs 3.08 +/- 1.35, p <0.01) compared with healthy subjects. Brachial artery FMD, however, was not different from that of the healthy subjects. Furthermore, neither hyperemic perfusion nor perfusion reserve was correlated with FMD in the patients with IDC, whereas the healthy subjects demonstrated a positive correlation between FMD and perfusion reserve (r = 0.57; p = 0.04). Thus, abnormal myocardial perfusion characterizes patients with IDC. Myocardial perfusion reserve and peripheral endothelial function do not parallel each other in patients with IDC.

Brachial Artery↗

PubMed2006

Endothelial function in young subjects with vaso-vagal syncope.

BACKGROUND: The aim of this study was to determine whether endothelial function and inappropriate peripheral vasomotion have a significant role in the pathogenesis of neurally mediated syncope. METHODS: In 16 patients (mean age 28.2+/-5.8 years) with previous vaso-vagal syncope and in matched healthy subjects, endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent response to glyceryl trinitrate (GTN), 25 mug, were measured in the brachial artery from high-resolution ultrasonography. Heart rate variability (HRV) analysis at rest and during tilt test was compared between two groups. RESULTS: In the subjects with positive tilt test, all HRV parameters were significant higher respect to subjects with negative tilt test (P<0.001). The patients with positive tilt test, showed persistent, marked variability of heart rate (HR), due to increased vagal activity with withdrawal sympathetic tone and consequently reduction of blood pressure (BP) (-30.4+/-4.2 mmHg, P<0.001) accompanied by a decrease in HR (-24.3+/-4.5 beats/min, P<0.001) compared to negative tilt test subjects. These findings prove the real presence of vagal hypertone in patients with syncope. In our study, HR reached values lower than 40 beats/min. FMD in patients with neurally mediated syncope were significantly greater than those in controls (respectively, 9.2+/-2.8% vs. 4.6+/-1.4%, P<0.01) whereas no differences were shown in the response to GTN (18.4+/-4.4% vs. 16.1+/-4.2%, n.s.). CONCLUSIONS: The augmented endothelial function and the abnormal vasodilation of peripheral arteries in association with bradycardia play an important role in the development of vaso-vagal syncope in young subjects.

Adult↗

PubMed1998

Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomized, double-blind study.

OBJECTIVES: We sought to determine whether 6 months of treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril can improve conduit artery endothelial function in young subjects with insulin-dependent diabetes mellitus (IDDM). BACKGROUND: Endothelial dysfunction is an early event in atherogenesis and has been demonstrated in young subjects with IDDM. ACE inhibitors have been shown to enhance conduit artery endothelial function in animal experiments and in patients with established coronary atherosclerosis, although their effect in IDDM is not known. METHODS: Ninety-one subjects (mean age 30.9 years, range 18 to 44) with stable IDDM but no clinical evidence of vascular disease were randomized to receive enalapril (20 mg once daily) (46 subjects) or placebo (45 subjects) in a randomized, double-blind, parallel-group study. Brachial artery flow-mediated dilation (FMD), an endothelium-dependent stimulus, and response to glyceryl trinitrate (GTN), which acts directly on vascular smooth muscle, were assessed noninvasively by means of high resolution external vascular ultrasound at baseline and after 12 and 24 weeks of treatment. RESULTS: FMD was inversely correlated with total cholesterol (r=0.22, p=0.041) but not with any diabetic variables. Treatment with enalapril had no significant effect on FMD (p=0.67) or response to the endothelial-independent dilator GTN (p=0.45). CONCLUSIONS: These data suggest that impairment of endothelial-dependent dilation in young subjects with IDDM is not improved by treatment with the ACE inhibitor enalapril. This lack of improvement may reflect the complex nature of vascular disease in IDDM, which can affect both endothelial and smooth muscle function.

Adolescent↗

PubMed2004

The postprandial state does not impair endothelial function in women with type 2 diabetes irrespective of glycaemic control.

AIMS/HYPOTHESIS: The postprandial state has been shown to be associated with endothelial dysfunction, a predictor of cardiovascular morbidity. In type 2 diabetes, postprandial metabolic excursions are prolonged and exaggerated, but less pronounced if glycaemic control is optimised. We investigated the impact of improved glycaemic control on endothelial function in the postprandial state. METHODS: We studied 19 postmenopausal women with type 2 diabetes and ten non-diabetic subjects. Participants with diabetes were re-studied 3 months after intensive glucose regulation. We measured forearm blood flow by strain gauge plethysmography during rest, during acetylcholine infusion and post ischaemia in the fasting state, and again 3 hours after a mixed meal (660 kcal, 55% fat). RESULTS: Endothelium-dependent vasodilation was impaired in the diabetic group (p<0.005) and improved following an HbA1c reduction of 0.96% (p<0.05 for high-dose acetylcholine infusion). Postprandial metabolic excursions were higher in the diabetic group (p<0.001, p<0.01 and p<0.05 for glucose, insulin and triglycerides respectively). Resting forearm blood flow increased in all groups after the meal (p<0.005). There was no difference in fasting and postprandial endothelium-dependent vasodilation before and after improved glucose regulation in either group. CONCLUSIONS/INTERPRETATION: The postprandial state does not impair endothelial function in non-diabetic women and does not make pre-existing endothelial dysfunction worse in women with type 2 diabetes, irrespective of glycaemic control.

Aged↗

PubMed2004

Effect of spironolactone on endothelial function in patients with congestive heart failure on conventional medical therapy.

We prospectively studied the effect of spironolactone, an aldosterone antagonist, on endothelial function in patients with advanced congestive heart failure (CHF) using the brachial artery reactivity method. Twenty patients optimized on conventional CHF therapy were treated with spironolactone, and brachial artery flow- mediated dilation was measured at baseline and at 4 and 8 weeks. Spironolactone improved endothelial function at 4 weeks, and sustained the improvement at 8 weeks, in patients with CHF on conventional medical therapy, presumably due to reversal of aldosterone impairment of endothelial nitric oxide activity.

Aged↗

PubMed2005

Selective COX-2 inhibition with different doses of rofecoxib does not impair endothelial function in patients with coronary artery disease.

In this study, we investigated the effects of both 25 and 50 mg daily doses of rofecoxib on the endothelial functions of patients with coronary artery disease (CAD). For this purpose, 34 patients with documented severe CAD and who were under aspirin treatment (300 mg/day) were randomized to receive 4 weeks of treatment with a placebo (n = 10, group I), rofecoxib 25 mg/day (n = 12, group II), and rofecoxib 50 mg/day (n = 12, group III). Brachial artery vasodilator responses were measured in order to evaluate endothelial function. The percentage of change in endothelial-dependent vasodilation in groups I, II, and III were similar at the baseline level and showed no significant change after treatment (6.2+/-3.9% vs. 5.9+/-3.1% and 5.8+/-3.3% vs. 5.6+/-3.8% and 6.1+/-4.5% vs. 5.8+/-4.1%, respectively; P > 0.05). Compared with the baseline, endothelium-independent vasodilatation, as assessed by nitroglycerine (NTG), remained unchanged after the treatment period (11.2+/-6.9% vs. 10.3+/-7.1% and 11.2+/-6.3% vs. 9.9+/-5.1% and 9.5+/-4.9% and 8.8+/-4.6%, respectively; P> 0.05). Treatment with both doses also showed no significant effects on high-sensitivity C-reactive protein (hs-CRP) levels and resting arterial diameters (P > 0.05). In conclusion, 4 weeks of treatment with standard and high doses of rofecoxib showed no significant effects on either endothelial-dependent or independent vasodilator response or plasma hs-CRP levels in patients with severe CAD taking concomitant aspirin.

Aged↗

PubMed2004

Hormone therapy impairs endothelial function in postmenopausal women with type 2 diabetes mellitus treated with rosiglitazone.

Diabetes and ovarian senescence are associated with impaired endothelial function and altered arterial mechanical properties. Alterations in normal vascular structure and functioning are the primary cause of mortality and morbidity with type 2 diabetes. Similarly, after menopause, women experience an increase in the rate of cardiovascular disease. Thiazolidinediones have exhibited a number of antiatherogenic actions in populations with type 2 diabetes. The effect of thiazolidinediones in combination with hormone therapy (HT) in postmenopausal women is, however, unknown. To assess whether HT (transdermal estradiol 50 microg and micronized progesterone (100 mg/d) affects vascular function, 21 women receiving rosiglitazone were randomly assigned to receive HT or placebo for 12 wk in a double-blind crossover design. Measures of glycemic control, lipids, blood pressure, flow-mediated dilation, and distensibility index were undertaken at baseline and after each treatment. As a result, flow-mediated dilation was significantly reduced (15.3 +/- 3.8 to 6.6 +/- 1.6%, P = 0.02) with HT, whereas lipids, blood pressure, and distensibility index were unchanged. Placebo had no significant affect on any variables. Thus, the addition of HT to rosiglitazone treatment attenuates endothelial function without altering other cardiovascular risk factors. Caution should, therefore, be exercised when considering combined treatment with thiazolidinedione and HT.

Aged↗

PubMed2005

Microvascular endothelial function in subjects with Type 2 diabetes and the effect of lipid-lowering therapy.

AIMS: Abnormalities of microvascular and endothelial function are present in subjects with Type 2 diabetes. Although statin therapy improves cardiovascular risk in diabetes, dyslipidaemia in diabetes may be more responsive to combined statin and fibrate therapy. We examined the effect of cerivastatin and fenofibrate on microvascular function in subjects with Type 2 diabetes with no clinical evidence of cardiovascular disease and near normal lipid levels. METHODS: Age-, sex-, lipid- and blood pressure-matched subjects with Type 2 diabetes were randomized in double-blind fashion to one of four treatment groups: group 1 placebo/placebo (n=12), group 2 fenofibrate/placebo (n=10), group 3 cerivastatin/placebo (n=20) and group 4 cerivastatin/fenofibrate (n=11). The subjects were recruited from the Lipid in Diabetes Study. Microvascular function was assessed by skin blood flow response to iontophoresis of acetylcholine and sodium nitroprusside and by skin maximum hyperaemia to local heating. Measurements were carried out at baseline and 3 months later. RESULTS: Although all lipid parameters improved in groups 2-4 after 3 months' therapy, no difference was detected in skin blood flow to iontophoresis or maximum hyperaemia in any of the groups. Highly sensitive c-reactive protein (Hs-CRP) did not change with therapy. CONCLUSIONS: In conclusion, we were unable to demonstrate any improvement in microvascular endothelial function in non-hyperlipidaemic Type 2 diabetic subjects treated with single or combination lipid-lowering therapy.

Adult↗

PubMed2004

[Effect of tobacco smoking on endothelial function in patients with coronary arteriosclerosis].

Smoking is one of the most important risk factors of atherosclerosis and ischaemic heart disease. Endothelial dysfunction is a pathological result of smoking. The aim of the study was to examine the influence of cigarette smoking on biochemical parameters of endothelial function in persons with angiographically confirmed coronary arteries atherosclerosis. The study group included 117 men: 55 patients (mean age 58.8 +/- 10.4) with ischaemic heart disease and 62 healthy subjects (mean age 47.1 +/- 9.3) of control group. In all patients blood lipid concentrations, biochemical parameters of endothelial function (nitric oxide, endothelin-1, sICAM, selectin-E), and inflammation parameters (interleukin-1 beta, interleukin-6) were measured. In a group of smoking patients both: with atherosclerosis and in control subjects nitric oxide (NO) concentrations in serum were decreased in comparison to nonsmokers. In patients with diagnosed coronary arteries atherosclerosis interleukin-6 and sICAM concentrations were increased in comparison to non-smokers. It is concluded that cigarette smoking activates or maintains inflammatory reaction in vessels with atherosclerotic changes.

Adult↗

PubMed2004

Relation of endothelial nitric oxide synthase gene to plasma nitric oxide level, endothelial function, and blood pressure in African Americans.

BACKGROUND: The role of eNOS gene polymorphisms on plasma nitrite or nitrate (NOx) level, endothelial function, and blood pressure (BP) remains unclear. METHODS: We estimated the relationship of eNOS polymorphisms (the T(-786)C in the 5'-flanking promoter region, T(-786)C; 27-bp repeat in intron 4, eNOS4; and Glu298Asp in exon 7, G894T) with plasma NOx level, brachial endothelial function assessed by ultrasound measure of brachial artery flow-mediated dilation (FMD), and BP in 60 healthy African Americans, 30 men and 30 women aged 18 to 73 years. RESULTS: Among them, 73.1%, 23.9%, and 3.0% carried TT, TC, and CC of T(-786)C, respectively, 14.5%, 27.5%, 53.6%, and 1.4% carried aa, ab, bb, and bc of eNOS4 polymorphism, respectively, and 70.4%, 23.9%, and 5.6% carried GG, GT, and TT of G894T, respectively. G894T and eNOS4 were observed in linkage disequilibrium. Mean values of age, plasma NOx, FMD, systolic and diastolic BPs were not significantly different (P >.05) by eNOS polymorphisms. Plasma NO(x) level was found to be associated with systolic BP (r = 0.51, P =.03), and diastolic BP (r = 0.41, P =.08), but not with FMD, in individuals with "a" allele of eNOS4 polymorphism after adjustment for age, body mass index, serum glucose, and smoking status. CONCLUSIONS: We reveal a positive association between plasma NOx level and BP in normotensive African Americans who carry the "a" allele of eNOS4. Because the frequency of the rare allele "a" is significantly higher in African Americans than in other ethnic groups, this finding may provide a clue to understanding the genetic susceptibility to hypertension in African Americans.

Adolescent↗

PubMed2003

Lifestyle modification improves endothelial function in obese subjects with the insulin resistance syndrome.

OBJECTIVE: Endothelial dysfunction has been reported in type 2 diabetic patients and in obese subjects with insulin resistance syndrome (IRS). This study evaluates the effects of weight reduction and exercise on vascular reactivity of the macro- and the microcirculation in obese subjects with IRS. RESEARCH DESIGN AND METHODS; We studied 24 obese subjects (9 men and 15 women, age 49.3 +/- 1.9 years, BMI 36.7 +/- 0.94 kg/m(2), mean +/- SEM) with IRS at baseline and after 6 months of weight reduction and exercise. Brachial artery flow-mediated dilation (FMD) and response to sublingual glyceryltrinitrate (GTN) were assessed by high-resolution ultrasound. Microvascular reactivity was evaluated by the laser-Doppler perfusion imaging after iontophoresis of acetylcholine and sodium nitroprusside. We also measured plasma levels of soluble intercellular adhesion molecule (sICAM), vascular adhesion molecule, von Willebrand factor, plasminogen activator inhibitor-1 (PAI-1) antigen, and tissue plasminogen activator antigen. RESULTS: This intervention resulted in 6.6 +/- 1% reduction in body weight (P < 0.001) and significant improvement of insulin sensitivity index (2.9 +/- 0.36 vs. 1.9 +/- 0.33 [10(-4) x min(-1) x ( microU ml(-1))], P < 0.001). FMD significantly improved (12.9 +/- 1.2% vs. 7.9 +/- 1.0%, P < 0.001), whereas response to GTN and microvascular reactivity did not change. Similar observations were seen when the subjects were subclassified according to their glucose tolerance to normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes. sICAM and PAI-1 significantly decreased (251.3 +/- 7.7 vs. 265.6 +/- 9.3 ng/ml, P = 0.018 and 36.2 +/- 3.6 vs. 48.6 +/- 3.9 ng/ml, P = 0.001, respectively). The relationship between percentage weight reduction and improved FMD was linear (R(2) = 0.47, P = 0.001). CONCLUSIONS: We conclude that 6 months of weight reduction and exercise improve macrovascular endothelial function and reduces selective markers of endothelial activation and coagulation in obese subjects with IRS regardless of the degree of glucose tolerance.

Blood Flow Velocity↗

PubMedDate not supplied

Value of peripheral vascular endothelial function in the detection of relative myocardial ischemia in asymptomatic type 2 diabetic patients who underwent myocardial perfusion imaging.

BACKGROUND: Endothelial dysfunction precedes overt atherosclerosis and is present in patients with type 2 diabetes mellitus (T2DM). Myocardial perfusion imaging (MPI) is an effective method of detection of coronary artery disease (CAD); however, the relationship between endothelial function and MPI in asymptomatic patients with T2DM has not been examined. METHODS AND RESULTS: This study used a subset of the population from the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. Endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIV) were measured by use of brachial artery ultrasonography in 75 asymptomatic patients with T2DM (56 men; mean age, 58.6 +/- 6.4 years; mean duration of diabetes, 8.4 +/- 7.5 years) who underwent adenosine MPI. Of the patients, 15 (20%) had evidence of relative ischemia (MPI(+)) whereas 60 (80%) had a normal study (MPI(-)). Both EDV (3.5% +/- 3.7% vs 4.5% +/- 6.6%, P = not significant) and EIV (15.1% +/- 7.5% vs 16.8% +/- 8.4%, P = not significant) were similar in the 2 groups. On the basis of a receiver-operator analysis, an EDV response of 8% was selected as a cut point, with a negative predictive value of 93% (13/14 subjects with EDV >or=8% were MPI(-)). CONCLUSIONS: Endothelial function in asymptomatic patients with T2DM is not associated with the presence of relative myocardial ischemia by MPI; however, an EDV of 8% or greater has a high negative predictive value for the exclusion of CAD.

Adult↗

PubMed2002

Aggressive lipid lowering does not improve endothelial function in type 2 diabetes: the Diabetes Atorvastatin Lipid Intervention (DALI) Study: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Endothelial dysfunction is considered an important early marker of atherosclerosis and cardiovascular risk and is currently used as a surrogate end point for cardiovascular risk in clinical trials. Type 2 diabetic patients show a characteristic dyslipidemia. Aggressive lipid lowering might be an effective method to improve endothelial function in these patients. RESEARCH DESIGN AND METHODS: A randomized, double-blind, placebo-controlled trial was completed to study the effect of 30 weeks' administration of atorvastatin 10 mg and 80 mg on endothelial function, as assessed by B-mode ultrasound of the brachial artery, in 133 patients with type 2 diabetes without a history of cardiovascular disease. RESULTS: Patients with diabetes and diabetic dyslipidemia had considerable endothelium-dependent and endothelium-independent dysfunction; mean flow-mediated vasodilation (SD) was 3.16% (3.56), and mean response on sublingual nitroglycerin was 6.58% (6.04). Despite substantial lowering of all atherogenic lipid parameters, no improvement of endothelium-dependent vasodilatation was found (P > 0.8). CONCLUSIONS: We observed considerable baseline endothelium-dependent and endothelium-independent dysfunction in patients with diabetes and diabetic dyslipidemia without a history of cardiovascular disease. Aggressive lipid lowering by administration of atorvastatin, resulting in substantial improvement of the lipid profile, did not reverse endothelial dysfunction.

Anticholesteremic Agents↗

PubMed2006

Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function.

OBJECTIVES: We sought to investigate whether the addition of walnuts or olive oil to a fatty meal have differential effects on postprandial vasoactivity, lipoproteins, markers of oxidation and endothelial activation, and plasma asymmetric dimethylarginine (ADMA). BACKGROUND: Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal. METHODS: We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals. RESULTS: In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal. CONCLUSIONS: Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells.

Brachial Artery↗

PubMed2001

Vascular endothelial function and oxidative stress mechanisms in patients with Behçet's syndrome.

OBJECTIVES: We sought to test the hypothesis that vascular endothelial function is impaired in Behçet's syndrome and reflects increased levels of oxidative stress. BACKGROUND: Behçet's syndrome is a multisystem inflammatory disorder commonly complicated by vascular thrombosis and arterial aneurysm formation. The precise mechanisms underlying vascular disease in Behçet's syndrome are not known. METHODS: We studied 19 patients with Behçet's syndrome (18 to 50 years old, 9 men) and 21 healthy volunteers (18 to 50 years old, 10 men). Brachial artery flow-mediated dilation (endothelium-dependent), and nitroglycerin (NTG)-induced dilation (endothelium-independent) were measured. To investigate oxidative stress mechanisms, vascular studies were repeated 1 h after administration of vitamin C (1 g, intravenous) in 12 patients and 12 control subjects. RESULTS: Flow-mediated dilation was reduced in patients with Behcet's syndrome as compared with control subjects (0.7 +/- 0.9% vs. 5.7 +/- 0.9%, p = 0.001). In contrast, there were no significant differences in the brachial artery diameter (4.2 +/- 0.2 vs. 4.0 +/- 0.2 mm, p = 0.47) or NTG-induced dilation (19.7 +/- 1.9% vs. 19.7 +/- 1.2%, p = 0.98). In regression analysis, Behçet's syndrome was associated with impaired flow-mediated dilation independent of age, gender, brachial artery diameter, blood pressure, cholesterol and glucose. Vitamin C increased flow-mediated dilation in Behçet's syndrome (0.2 +/- 0.7% to 3.5 +/- 1.0%, p = 0.002), but not in control subjects (4.3 +/- 0.6% to 4.7 +/- 0.4%, p = 0.51). In both groups, NTG-induced dilation and brachial artery diameter were unchanged after vitamin C treatment. CONCLUSIONS: Vascular endothelial function is impaired in Behcet's syndrome and can be rapidly improved by vitamin C treatment. Our results support a role for oxidative stress in the pathophysiology of Behçet's syndrome and provide a rationale for therapeutic studies aimed at reducing vascular complications in this disorder.

Adolescent↗

PubMed1998

Cholesterol, endothelial function and cardiovascular disease.

Hypercholesterolaemia is associated with endothelial dysfunction and increased risk of atheromatous disease. Although endothelial dysfunction has been demonstrated early in the course of the disease process, it remains difficult to establish a causal relationship. Despite this, endothelial function has been used as a surrogate marker in small trials to identify and assess the effectiveness of therapeutic interventions to reduce cardiovascular mortality, before large scale clinical trials are undertaken. Recently, arterial stiffness has emerged as an independent risk factor for cardiovascular disease and may provide a link between hypercholesterolaemia, endothelial dysfunction, hypertension and stroke.

Animals↗

PubMed2003

Effect of statin therapy added to ACE-inhibitors on blood pressure control and endothelial functions in normolipidemic hypertensive patients.

OBJECTIVE: Endothelium-dependent vasodilatation is impaired in hypertension. Statins have been shown to improve endothelial functions in hyperlipidemic subjects. We aimed to investigate the effect of statins on endothelium-dependent flow mediated dilatation (FMD) and blood pressure (BP) in normocholesterolemic hypertensive patients. METHODS: This randomized prospective study consisted of 56 patients with newly diagnosed essential hypertension. All patients received angiotensin converting enzyme (ACE) inhibitor lisinopril (5 mg/day) as antihypertensive therapy, and half of them were randomized to simvastatin(20mg/day) irrespective of serum lipid levels. All subjects underwent brachial artery ultrasonographic examination for the measurement of FMD before randomization and at the end of 12 weeks treatment. RESULTS: A total of 39 patients completed the study (21 patients in the statin + ACE inhibitor group, and 18 patients in the ACE-inhibitor alone group). Blood pressure levels were substantially reduced in both groups after treatment. In statin+ ACE-inhibitor group systolic pressure reduced by 23% (p=0.0001) and diastolic BP reduced by 23% (p=0.0001). In ACE-inhibitor alone group these ratios were 20% (p=0.001) and 21% (p=0.001), respectively. Meanwhile, pulse pressure (PP) decreased by 25% in statin+ ACE-inhibitor group (P=0.0001) and by 16% in ACE inhibitor-alone group (p=0.0051). Baseline FMD was significantly impaired in overall patients with hypertension as compared with healthy controls (13+/-8 vs. 24+/-8 %, P = 0.001). After treatment FMD decreased by 23% in lisinopril alone group (p=0.054). There were no correlations between FMD improvement, LDL reduction, BP or PP changes in both groups. CONCLUSION: Addition of simvastatin to ACE-inhibitor treatment in newly diagnosed hypertensive patients with normal cholesterol levels, significantly reduced PP and facilitated BP control, but did not affect endothelium-dependent dilatation. Further long-term large scale studies are needed to clarify the effect of various statins on endothelial functions of either hypercholesterolemic or normocholesterolemic hypertensive patients.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2004

Sex influences endothelial function in sleep-disordered breathing.

BACKGROUND: The bases for the association between sleep-disordered breathing (SDB) and cardiovascular disease are poorly understood. Endothelial dysfunction, assessed with brachial artery ultrasonography, may predict cardiovascular risk and represent preclinical vascular disease. We determined whether flow-mediated dilation (FMD) and peak blood flow (PBF) increase after cuff occlusion is altered with SDB. METHODS: 193 participants (58% women) in a cohort study were studied with overnight polysomnography and subsequent brachial artery ultrasonography. SDB was quantified using the apnea-hypopnea index (AHI) and indexes of overnight desaturation and arousal frequency. Two-dimensional and Doppler-velocity measurements of the brachial artery were obtained at baseline and after 5 minutes of upper-arm cuff occlusion. FMD and PBF were defined as the percentage changes from baseline in brachial artery diameter and flow, respectively. RESULTS: In the entire sample, the AHI was inversely associated with both FMD (r = -0.30, P < .001) and PBF (r = -0.20, P < .001). However, sex-stratified univariate analyses showed that these relationships were exclusive to women. Specifically, FMD was significantly lower in women with an AHI > or = 15 than in women with lower AHI scores (P < .005), with no relationship between AHI and FMD in men. Additionally, PBF decreased significantly with increasing AHI (r = -0.29, P = .010) in women alone. Statistical modeling, adjusting for body mass index, age, and other covariates, similarly showed that SDB severity significantly influenced FMD and PBF, with significant interactions between sex and AHI, reinforcing that the associations between SDB severity and endothelial function were stronger in women than in men. CONCLUSIONS: Moderate levels of SBD are associated with impaired conduit and resistance endothelial function in women. Women with SDB may be more vulnerable to early SDB-related cardiovascular disease than are men.

Adult↗