Background Morphologic changes of the vascular endothelium are common in patients with systemic sclerosis and Raynaud’s phenomenon. The aim of this study was to evaluate the endothelium-dependent ...vasodilatation and endothelium-independent vasodilatation and to examine the effects of short-term estrogen administration on vascular responses in these patients.
Methods and Results The study included 12 female patients with systemic sclerosis and Raynaud’s phenomenon (aged 49 ± 14 years) and 12 age- and sex-matched healthy control subjects. With the use of high-resolution ultrasound imaging, brachial artery diameter was measured at rest, during reactive hyperemia (endothelium-dependent response), and after administration of sublingual nitroglycerin (endothelium-independent dilatation). Intima-media thickness of the common carotid artery was also measured. Baseline diameter was similar in patients and control subjects; intima-media thickness was significantly higher in patients (0.83 ± 0.3 vs 0.46 ± 0.2 mm,
P = .002) than in control subjects. Flow-mediated dilatation was reduced in patients (3.6% ± 7% vs 11.9% ± 4.6%,
P = .003); endothelium-independent dilatation also was reduced in patients with Raynaud’s phenomenon (14% ± 7% vs 23% ± 6%,
P = .003). Vascular responses in 10 patients were examined 15 minutes after administration of conjugated estrogens (25 mg intravenously); there was a significant increase of endothelium-dependent dilatation after estrogen administration (1.7% ± 4% to 6.3% ± 4%,
P = .01), whereas endothelium-independent dilatation did not change (13.4% ± 8% to 15.5% ± 7%, not significant).
Conclusions Endothelium-dependent vasodilatation and endothelium-independent vasodilatation are impaired in patients with Raynaud’s phenomenon secondary to systemic sclerosis, whereas intima-media thickness is increased. Short-term estrogen administration can improve endothelial dysfunction in this group of patients. (Am Heart J 1998;136:905-12.)
Hyperhomocysteinemia has been recognised as an independent cardiovascular risk factor, while statins have been reported to have pleiotropic effects other than lipid lowering. In our study we sought ...to evaluate the possible effect of short-term administration of simvastatin on homocysteine (Hcy) and other established serum proatherogenic and inflammatory markers in essential hypertensive patients. Our study population consisted of 18 untreated mild essential hypertensive patients (9 men, mean age: 51.2±10.9 years, office blood pressure = 149/96 mmHg). All subjects received simvastatin (40mg/day) for a period of 1 month. Venous blood samples were drawn before and after the period of treatment with simvastatin in order to evaluate lipid, lipoprotein-a (Lp-a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), fibrinogen, uric acid, homocysteine, folic acid, vitamin B12, high sensitivity-CRP (hsCRP) levels, by standard methodology. For the pooled population BMI was 27.2±3.6 kg/m2, left ventricular mass index was 106±35.1 g/m2, relative wall thickness was 0.45±0.07 and hsCRP levels were 1.5±0.3 mg/l. After 1 month on simvastatin, there was a significant reduction in total cholesterol (215.1±40.7 vs 156.0±29.2 mg/dl, p<0.001), triglycerides (114.1±30.9 vs 89.6±27.8 mg/dl, p<0.05), LDL (141.4±29 vs 89.6±21.6 mg/dl, p<0.001), ApoB (101.6±19.2 vs 71.8±15 mg/dl, p<0.001), uric acid (5.8±1.2 vs 5.4±1.1 mg/dl, p<0.05), homocysteine (13.6±7.3 vs 12.7±7.4 μmol/l, p<0.05). In all subjects, apoA1 and hs-CRP did not exhibit any statistically significant attenuation (p=NS, for all cases). Moreover, the reduction of Hcy serum levels was not correlated with the observed reductions in total cholesterol, triglycerides, LDL, ApoB and uric acid values (p=NS, for all cases). Even in newly diagnosed essential hypertensive subjects, short-term administration of simvastatin resulted in a significant and independent attenuation of Hcy serum levels. These findings may elucidate the diverse pathophysiological mechanisms by which statins reduce cardiovascular risk, in this setting.
Several serum markers have been recognized as risk factors for target organ damage, while carotid intima-media thickness (IMT) has been established as an independent risk factor for cardiovascular ...events. In our study, we sought to validate the measurement of several biochemical risk factors as markers of carotid atherosclerosis in essential hypertensive subjects. This study included 24 untreated, mild essential, non-smokers hypertensive patients (13 men, mean age: 50 ±11.7 years) who underwent 24h ambulatory blood pressure monitoring in order to exclude white-coat hypertension. All subjects underwent B-mode ultrasonography of the carotid arteries to determine IMT and the presence of atheroma plaques of the common and internal carotid artery and carotid bulb. Venous blood samples were drawn from all participants in order to evaluate lipid and lipoprotein-a (Lp-a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), fibrinogen, uric acid, homocysteine and hsCRP levels, by standard methodology. For the pooled population, BMI was 27.6±5.1 kg/m2, cholesterol was 211.2±43.3 mg/dl, triglycerides were 115±56.2 mg/dl, HDL was 57.1±15 mg/dl, LDL was 139±31 mg/dl, Lp-a was 46±78 mg/dl, ApoA1 levels were 124.1±15.2 mg/dl, ApoB was 101.6±18.7, hs-CRP levels were 2.16±2 mg/l, fibrinogen was 270.8±49 mg/dl, uric acid levels were 5.8±1.4 mg/dl, homocysteine was 13.2±6.2 μmol/l. In the univariate model, IMT of the internal carotid artery was correlated with levels of triglycerides (r=0.432, p=0.039), uric acid (r=0.610, p=0.002), homocysteine (r=0.507, p=0.014) and ApoA1 (r=-0.457, p=0.028). Furthermore, in stepwise regression analysis only serum levels of uric acid and homocysteine remained significant after adjustment for all parameters analyzed (p=0.002 and p=0.016 respectively). In essential hypertensive subjects, serum levels of uric acid and homocysteine are closely related to carotid IMT, independently of a wide range of established proatherogenic and inflammatory mediators.
Statins have been reported to improve blood pressure control in essential hypertensive subjects via diverse pathophysiological mechanisms, while salt sensitivity is an emerging cardiovascular risk ...factor. In this study, we sought to investigate the possible effects of short-term administration of simvastatin on blood pressure levels in salt sensitive and salt resistant essential hypertensive subjects. Eighteen untreated mild essential hypertensive patients (9 men, age 51.2±10.9 years) were screened for salt sensitivity by means of an established protocol. All subjects underwent 24h ambulatory BP monitoring before and after 1 month of treatment with simvastatin (40mg/day). Venous blood samples were drawn before and after statin administration period for determination of lipid, lipoprotein-a, apolipoprotein A1 and apolipoprotein B levels. For the pooled population BMI was 27.2±3.6 kg/m2, left ventricular mass index was 106±35.1 g/m2 and relative wall thickness was 0.45±0.07. Four patients were classified as salt sensitive (SS) (2 men, 60±9 years), while 14 were salt resistant (SR) (7 men, 60±10 years). After 1 month on simvastatin, only SS patients, presented significant reductions in office systolic BP (155±12.9 vs 130±18.2 mmHg, p<0.05), 24-h diastolic BP (85.9±5.7 vs 76.3±4.3 mm Hg, p<0.05), 24-h mean BP (104.4±5.1 vs 93.3±7.5 mm Hg, p<0.05), daytime diastolic BP (89.1±7.6 vs 78.9±6 mm Hg, p<0.05), daytime mean BP (107.5±8.5 vs 95.1±8.3 mm Hg, p<0.05), while patients in the SR group did not exhibit any significant reduction in 24h BP levels (p=NS). Moreover, there was no correlation between the reductions of 24h BP in the SS group and the reductions of the lipid parameters (p=NS). In newly diagnosed essential hypertensive subjects, short-term administration of simvastatin resulted in a significant attenuation of BP values in salt sensitive hypertensives, independently of lipid lowering, suggesting a possible link between salt sensitivity and the pleiotropic mechanisms of statins action. These findings suggest that salt sensitive patients may benefit more from the pleiotropic effects of statins, in the same setting.
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