Metabolic syndrome and preclinical atherosclerosis: focus on femoral arteries.

Several evidences revealed the relationship between the earliest stages of atherosclerosis and the components of metabolic syndrome. The aim of this study was to disclose preclinical atherosclerotic lesions in a cross-sectional observational study involving 147 patients with metabolic syndrome by the assessment of brachial flow-mediated vasodilation (FMV) and intima-media thickening at both carotid and femoral sites. The purpose was to investigate the association of this metabolic disorder with prevalent atherosclerotic damage in different vascular sites. A control group of 87 healthy subjects was also investigated. Patients had lower values of FMV and a higher mean intima-media thickness (IMT) at both the carotid and femoral sites with respect to controls. Flow-mediated vasodilation had a positive correlation with high-density lipoprotein (HDL) cholesterol and a negative one with low-density lipoprotein (LDL) cholesterol, glycemia, and insulinemia. Carotid mean IMT was directly related to LDL cholesterol and age, and inversely with HDL cholesterol; femoral mean IMT had a direct association with LDL cholesterol, triglycerides, glycemia, and insulinemia and an inverse correlation with HDL cholesterol and LDL size. LDL cholesterol, HDL cholesterol, insulin, and brachial artery diameter were predictive of brachial FMV (beta=-0.17, 0.21, -0.27, and -0.29, respectively; P<.05), whereas age, LDL cholesterol, and HDL cholesterol were independent predictors of mean carotid IMT (beta=0.19, 0.37, and -0.27, respectively; P<.05); on the other hand, LDL cholesterol, triglycerides, and insulin were independent predictors of mean femoral IMT (beta=0.32, 0.26, and 0.25, respectively; P<.05). In conclusion, the present study documented an altered endothelial function and intima-media thickening in patients with metabolic syndrome without overt cardiovascular disease. Moreover, it focused on the strong influence of metabolic syndrome on preclinical atherosclerotic lesions at the femoral site.

Plasma viscosity in isolated systolic hypertension: the role of pulse pressure.

Atherosclerosis is increasingly recognized as an inflammatory vascular disease, and high blood pressure (BP) has been suggested to exert a proinflammatory action. Whether plasma viscosity (PV), a major determinant of blood flow in microcirculation and a marker of systemic inflammation and cardiovascular risk, is increased in elderly subjects with isolated systolic hypertension is not known. In addition, the correlation of BP and its pulsatile component (ie, pulse pressure [PP]), with PV levels independent of the confounding effect of other cardiovascular risk factors has not been investigated. To this aim, we measured PV in 108 elderly men with never treated, uncomplicated isolated systolic hypertension, and in 60 healthy matched normotensive control subjects. The PV values were higher in hypertensive subjects than in controls (1.39+/-0.11 v 1.34+/-0.09 cP, P<.01). The PV showed a significant direct relation with both systolic BP (r=0.32) and PP (r=0.37, both P<.01), but not with diastolic BP (r=-0.03, P=.68). The PV was also directly associated with serum low-density lipoprotein cholesterol and triglycerides. In a multivariate analysis, PP was a significant predictor of PV levels when a consistent number of cardiovascular risk factors were simultaneously controlled for. In conclusion, PV is elevated in elderly subjects with isolated systolic hypertension. Systolic BP and PP appear to be major determinants of PV levels in these patients, independent of the potential proinflammatory action of traditional cardiovascular risk factors.

Increased postprandial lipemia in patients with normolipemic peripheral arterial disease.

METHODS: We evaluated the postprandial lipid metabolism in patients with normolipemic peripheral arterial disease (PAD) after the administration of an oral fat load. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL2 and HDL3 subfractions, triglycerides (TGs), lipoprotein(a), and LDL size were determined at baseline and for 8 hours after the meal. RESULTS: In patients with PAD, TGs increased significantly at the 4th, 6th, and 8th hours postprandially; in control subjects, TGs increased at the 4th and 6th hours. HDL decreased significantly at the 4th, 6th, and 8th hours in patients with PAD and at the 6th hour in control subjects. The magnitude of postprandial lipemia, expressed as "the area under the incremental curve for TGs," was higher in patients with PAD than in control subjects (770 +/- 476 vs 391 +/- 195 mg/dL at 8 hours, P <.05). Multiple-regression analysis showed that baseline TGs were positively related to the magnitude of postprandial lipemia (P =.01) and that LDL size was negatively related (P =.05). CONCLUSIONS: This is the first documentation of postprandial behavior in patients with normolipemic PAD, suggesting the relevance of postprandial lipoprotein metabolism in the pathogenesis of peripheral atherosclerosis.

Capillary rarefaction and abnormal cardiovascular reactivity in hypertension.

OBJECTIVE: To determine the effects of capillary rarefaction on cardiovascular reactivity and microcirculatory functioning in essential hypertension. DESIGN: Hypertension is associated with abnormal cardiovascular reactivity and increased vasoconstriction. Capillary rarefaction amplifies these abnormalities, which modify microcirculatory hemodynamics. Hence this study of the hemorheological pattern and the veno-arteriolar reflex in hypertensive patients and normotensive control subjects. METHODS: Sixty-one men with never-treated essential hypertension and capillary rarefaction (< 80 capillaries per field) and 20 age-matched and sex-matched controls underwent a strenuous cycle ergometer test to monitor, during exercise and recovery, the blood pressure profile and the hemorheological pattern: blood viscosity at low shear, hematocrit and leukocyte counts, soluble P-selectin levels, and red and white blood cell filterability rates. The veno-arteriolar reflex was determined by laser-Doppler flowmetry before exercise and at recovery.RESULTS Hypertensive men with < or = 72 capillaries per field had an abnormal hemorheological profile before exercise. The physiological response to exercise was observed only in the controls and in hypertensives with > or = 73 capillaries per field. Abnormal responses to exercise worsened as capillaries were more rarefied. At recovery, hemorheological parameters in hypertensives with 65-72 capillaries per field returned to baseline, remaining significantly (P < 0.05) different to control values. Variations in the hemorheological pattern in hypertensives with < 64 capillary per field persisted at recovery. The veno-arteriolar reflex followed the same pattern. CONCLUSION: A reduced microvascular network may contribute to abnormal cardiovascular reactivity and to exercise-induced rheological abnormalities in hypertension.

Mechanisms of high-density lipoprotein cholesterol effects on the endothelial function in hyperlipemia.

High-density lipoprotein-cholesterol (HDL-c) has a favorable influence on the endothelial function, but the mechanisms of this protective action are not fully understood. We studied lipid parameters, soluble adhesion molecules (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule [ICAM-1], E-selectin) oxidized low-density lipoproteins (LDL), and brachial-artery flow-mediated vasodilation (FMV) in 184 hyperlipemic patients (90 men, age 54 +/- 10 years, waist/hip circumference ratio 0.89 +/- 0.07, LDL-cholesterol [LDL-c] 4.9 +/- 1.3 mmol/L, triglycerides 1.8 +/- 0.9 mmol/L, HDL-c 1.3 +/- 0.5 mmol/L) after excluding those with current smoking, diabetes, hypertension, and vascular diseases. Patients were divided into 2 groups on the basis of HDL-c levels: < 1.03 mmol/L (n = 53) v >or= 1.03 mmol/L (n = 131). Patients with low HDL-c showed significantly lower LDL-c (P <.05), higher triglycerides (P <.001), higher body mass index (P <.02), lower FMV (3.7% +/- 2.0% v 4.9% +/- 3.4%, P <.002), higher VCAM-1 (1,195 +/- 395 ng/mL v 984 +/- 303 ng/mL, P <.01), and higher ICAM-1 (406 +/- 78 ng/mL v 364 +/- 68 ng/mL, P <.01). E-selectin and oxidized LDL showed no significant differences. In a multivariate age, oxidized LDL and brachial artery diameter predicted a lower FMV, while HDL-c was an independent predictor of a greater FMV (P =.003). Increasing levels of VCAM-1 and ICAM-1 were predicted by lower HDL-c, while higher oxidized LDL predicted higher VCAM-1 (P <.05). Our data suggest that in hyperlipemic subjects free of cardiovascular disease low HDL-c negatively modulates endothelial function through a lack of oxidation inhibition and a concomitant overexpression of adhesion molecules.

The influence of iloprost on blood rheology and tissue perfusion in patients with intermittent claudication.

BACKGROUND: In peripheral vascular disease (PVD), impaired blood viscosity (BV) plays a major role in residual microvascular perfusion. Indeed, during acute leg ischaemia factors influencing microvascular BV include the plasma fibrinogen concentration, red and white blood cell rheology, as well as platelet aggregation and activation. AIM: To assess the effects of Iloprost in patients with PVD. METHODS: The effects of an infusion of a single dose of Iloprost (from 0.5 up to a maximum of 2 ng/kg/min. over 6 hours) in 16 patients with stage II peripheral vascular disease on blood rheology and tissue perfusion were determined in a double-blind placebo-controlled study, using repeated treadmill exercise test to stress leg circulation. Blood viscosity at low shear, soluble P-selectin levels (expression of platelet activation), unfractionated leukocyte and erythrocyte filterability rates, plasma fibrinogen concentration, haematocrit, leukocyte and platelet counts and transcutaneous oxygen pressure (TcPO(2)) were measured in two matched groups of 8 PVD patients before and after Iloprost infusion. RESULTS: Controlled peripheral ischaemia generated an impaired haemorheological profile; Iloprost reduced the impairments in BV and the filterability rates of unfractionated leukocytes and erythrocytes, inhibited platelet activation, and improved erythrocyte deformability. These changes were associated with significant shortening of the TcPO(2) half recovery time (the drop of TcPO(2) occurs because the ischaemic skeletal muscle steals oxygen from the skin), indicating that ischaemic damage had been contained. CONCLUSIONS: Our results show that the infusion of a single dose of Iloprost in patients with PVD is associated with a significant improvement in microvascular functioning

Prognostic value of low and high ankle-brachial index in hospitalized medical patients.

BACKGROUND: Peripheral arterial disease (PAD) is frequently underdiagnosed in the clinical practice, leading to a lack of opportunity to detect subjects at a high risk for cardiovascular (CV) death. The ankle-brachial pressure index (ABI) represents a noninvasive, objective tool to diagnose PAD and to predict adverse outcome. METHODS: ABI was determined by means of Doppler velocimetry, in 707 patients, aged 50 years or older, consecutively hospitalized in an internal medicine ward, who were followed-up for at least 12 months in order to assess all-cause and CV mortality. RESULTS: Symptomatic PAD affected 8% of the population while the prevalence of PAD, defined as ABI <0.90, was 29%; high ABI (>1.40) was found in 8% of the patients. After a mean follow-up period of 1.6 years, both low and high ABI were independently associated with CV mortality with a hazard ratio of 1.99 (p=0.016) for low and 2.13 (p=0.04) for high ABI, compared with normal ABI (0.90-1.40). High ABI also independently predicted all-cause mortality with a hazard ratio of 1.77 (p=0.04). DISCUSSION: ABI measurement reveals a large number of individuals with asymptomatic PAD among those hospitalized in an internal medicine department. An increased mortality was observed in patients with both low and high ABI. Hospital admission for any reason may serve as an opportunity to detect PAD and start appropriate preventive actions.

The use of osteopathic manipulative treatment as adjuvant therapy in patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis associated with impaired endothelial function and intermittent claudication is the hallmark symptom. Hypothesizing that osteopathic manipulative treatment (OMT) may represent a non-pharmacological therapeutic option in PAD, we examined endothelial function and lifestyle modifications in 15 intermittent claudication patients receiving osteopathic treatment (OMT group) and 15 intermittent claudication patients matched for age, sex and medical treatment (control group). Compared to the control group, the OMT group had a significant increase in brachial flow-mediated vasodilation, ankle/brachial pressure index, treadmill testing and physical health component of life quality (all p<0.05) from the beginning to the end of the study. At univariate analysis in the OMT group there was a negative correlation between changes in brachial flow-mediated vasodilation and IL-6 levels (r=-0.30; p=0.04) and a positive one between claudication pain time and physical function score (r=0.50; p=0.05). In conclusion, despite the relatively few patients in our study, these results suggest that OMT significantly improves endothelial function and functional performance in intermittent claudication patients along with benefits in quality of life. This novel treatment combined with drug and lifestyle modification might be an effective alternative to traditional training based on exercise.