Anna Rita Roscini

Impaired flow-mediated vasoactivity during post-prandial phase in young healthy men.

Impaired flow-mediated vasodilation in large arteries is an expression of endothelial dysfunction and an established marker of early atherosclerosis. Post-prandial lipemia can induce an impairment of the endothelial function. The aim of our study was to evaluate the effects of post-prandial phase on flow-mediated vasodilation in a group of ten young (23 +/- 2 years) healthy men without cardiovascular risk factors, who underwent an oral fat-loading test. Flow-mediated vasodilation of the brachial artery and serum lipid profile were assessed under fasting conditions and 2, 4, 6 and 8 h after a high-fat meal. Triglycerides increased from 0.6 +/- 0.2 fasting to 1.1 +/- 0.5 and 1.3 +/-0.6 mmol/l at the 2nd and 4th hour (both P < 0.01), and decreased thereafter. Flow-mediated vasodilation fell significantly from 14.5 +/- 6.6% fasting to 3.5 +/- 1.5% and 4.0 +/- 2.2% at the 2nd and 4th hour (both P < 0.01), and returned to the basal values at the 6th and 8th hour. A strong inverse correlation was observed between the area under the incremental curve of post-prandial triglycerides (i.e. after subtraction of baseline triglycerides) and the area under the decremental curve of post-prandial flow-mediated vasodilation (r = -0.70, P = 0.025). No association was found between post-prandial vasodilation changes and fasting triglycerides, other lipid parameters or insulin. We conclude that a transient post-prandial impairment in brachial artery flow-mediated vasodilation is evident in young healthy men after a high-fat meal, and is closely associated with triglyceride levels. These data provide support for a role of post-prandial phase in vascular regulation in young healthy subjects.

Short-term atorvastatin treatment improves endothelial function in hypercholesterolemic women.

Endothelial dysfunction represents the earliest stage of atherosclerosis and is usually present in hypercholesterolemia. Treatment with statins has been shown to normalize endothelial function in middle-aged men with hypercholesterolemia. We evaluated the effect over time of atorvastatin on the endothelial reactivity in postmenopausal hypercholesterolemic women (mean age, 58 +/- 6 years), receiving atorvastatin, 10 mg daily (n = 20) or American Heart Association step 1 diet (n = 10) for 8 weeks. Lipid profile and brachial artery flow-mediated vasodilation (FMV) were determined at baseline and after 1, 2, 4, and 8 weeks. FMV increased progressively in subjects treated with atorvastatin, and the difference was significant (p < 0.05 vs. baseline) after the second week (baseline 3.8 +/- 3%; first week, 4.8 +/- 3%; second week, 9.2 +/- 3%; fourth week, 11.0 +/- 3%; eighth week, 11.7 +/- 3%). No significant changes were observed in subjects receiving diet (baseline, 3.1 +/- 4%; first week, 2.4 +/- 2%; second week, 2.9 +/- 2%; fourth week, 3.1 +/- 2%; eighth week, 3.3 +/- 2%; p = NS). In the atorvastatin group, low-density lipoprotein (LDL) cholesterol showed a significant decrease since the first week (baseline, 228 +/- 37 mg/dl; first week, 171 +/- 32; second week, 147 +/- 27; fourth week, 139 +/- 29; eighth week, 135 +/- 27; all p < 0.05). In the control group, LDL cholesterol showed a smaller but significant (p < 0.05) reduction after the second week (baseline, 226 +/- 17 mg/dl; first week, 225 +/- 16; second week, 220 +/- 17; fourth week, 203 +/- 27; eighth week, 198 +/- 27). In conclusion, hypercholesterolemic women treated with atorvastatin show a significant improvement in endothelial reactivity after as early as 2 weeks of therapy. The extent to which these beneficial effects are attributable to cholesterol reduction or to a direct effect of the drug remains to be established.

Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia.

Background:  Fasting and post‐prandial hypertriglyceridemia have been associated with endothelial dysfunction.

Is estimated cardiovascular risk higher in HIV-infected patients than in the general population?

Cardiovascular disease (CVD) is an increasing concern for human immunodeficiency virus (HIV)-infected patients, and risk assessment is recommended in routine HIV care. The absolute cardiovascular risk in an individual is determined by several factors, and various algorithms may be applied. To date, few comparisons of HIV patients with persons of the same age from the general population have been conducted. We hypothesized that the calculated risk of CVD may be increased in HIV patients. The probability for acute coronary events within 10 y (Framingham Risk Score) and the probability for fatal cardiovascular disease (SCORE algorithm) were assessed in 403 consecutive HIV-positive subjects free from overt cardiovascular disease, as well as in 96 age- and gender-matched control subjects drawn from the general population living in the same geographical area. The average 10-y risk for acute coronary events (Framingham Risk Score) was 7.0%±5% in HIV subjects and 6.3%±5% in the control group (p =0.32). The 10-y estimated risk for cardiovascular mortality (SCORE algorithm) was 1.23%±2.3% and 0.83%±0.9%, respectively (p =0.01). The main contributor to the increased CVD risk was the high proportion of smokers, but not an increase in cholesterol level. In conclusion, a limited increase in estimated risk of CVD was found in HIV-infected patients compared to the general population. In HIV-infected individuals other factors of less value in the general population and not included in any cardiovascular algorithm might be important. In our patients intervention to modify traditional risk factors should be addressed primarily towards modifying smoking habits.

Oral L-arginine administration attenuates postprandial endothelial dysfunction in young healthy males

Background: Endothelial dysfunction is considered the earliest stage of atherosclerosis. Postprandial phase is associated with a transient impairment of endothelial function concomitantly with the triglyceride‐rich lipoprotein increase. This phenomenon may be explained by the oxidative burden induced by triglyceride‐rich lipoproteins, reducing nitric oxide bioavailability.

Preclinical vascular damage in white postmenopausal women: the relevance of osteoprotegerin.

Osteoprotegerin (OPG) has recently been implicated in human atherogenesis. Abdominal obesity represents an established risk factor for the onset and development of atherosclerotic damage. The aim of the present study was to investigate the link between OPG and abdominal fat and the relationship to precocious features of atherosclerotic disease such as brachial flow-mediated vasodilation (FMV) and the intima-media thickening (IMT) in 195 white postmenopausal women (age range, 43-75 years). The study population was divided into 2 groups: group 1-waist circumference <80 cm and group 2-waist circumference > or = 80 cm. Group 2 had higher menopausal years, body mass index, low-density lipoprotein cholesterol, triglycerides, C-reactive protein, and carotid IMT. High-density lipoprotein cholesterol was higher in group 1. Afterward, these groups were divided on the basis of a cutoff value of OPG (6.85 pmol/L) that was the median of its distribution: patients with OPG < or = 6.85 pmol/L were OPG(-), and those with OPG >6.85 pmol/L were OPG(+). The OPG(+) subjects in both had lower brachial FMV and higher carotid IMT in comparison with OPG(-) subjects. At the multivariate regression analysis, waist circumference, high-density lipoprotein cholesterol, C-reactive protein, and OPG were predictors of carotid mean IMT (beta = 0.55, P = .001; beta = -0.14, P = .001; beta = 0.16, P = .001; and beta = 0.14, P = .05, respectively) and age, OPG, low-density lipoprotein cholesterol, and brachial diameter of brachial FMV (beta = -0.13, P = .05; beta = -0.25, P = .001; beta = -0.14, P = .024; and beta = 0.48, P = .001, respectively). The conclusions are as follows: first, OPG levels did not appear to be conditioned by a risk factor such as abdominal obesity; and second, OPG levels are mainly linked to the evidence of vascular damage. On this basis, we could speculate that OPG levels may be considered not a cardiovascular risk condition but a defense against atherosclerotic progression.

Visceral fat positively correlates with cholesterol synthesis in dyslipidaemic patients

Eur J Clin Invest 2011

Non-cholesterol sterols in different forms of primary hyperlipemias.

BACKGROUND AND AIMS We investigated the behaviour of non-cholesterol sterols, surrogate markers of cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol), in primary hyperlipemias. METHODS AND RESULTS We studied 53 patients with polygenic hypercholesterolemia (PH), 38 patients with familial combined hyperlipemia (FCH), and 19 age- and sex-matched healthy control subjects. In all participants, plasma sitosterol, campesterol and lathosterol were determined by gas chromatography coupled to mass spectrometry. To correct for the effect of plasma lipid levels, non-cholesterol sterol concentrations were adjusted for plasma cholesterol (10² μmol/mmol cholesterol). Patients with FCH were more frequently men, and had higher body mass index (BMI), fasting glucose, insulin and HOMA-IR. Lathosterol was higher in FCH than in pH or controls (p < 0.05). Campesterol was significantly lower in FCH (p < 0.05), while no differences were found between pH and controls. Sitosterol displayed higher values in pH compared to FCH (p < 0.001) and controls (p < 0.05). Spearmans rank correlations showed positive correlations of lathosterol with BMI, waist circumference, HOMA-IR, triglycerides, apoprotein B, and a negative one with HDL-cholesterol. Sitosterol had a negative correlation with BMI, waist circumference, HOMA-IR, triglycerides, and a positive one with HDL-cholesterol and apoprotein AI. Multivariate regression analyses showed that cholesterol absorption markers predicted higher HDL-cholesterol levels, while HOMA-IR was a negative predictor of sitosterol and BMI a positive predictor of lathosterol. CONCLUSIONS Our findings suggest the occurrence of an increased cholesterol synthesis in FCH, and an increased cholesterol absorption in pH. Markers of cholesterol synthesis cluster with clinical and laboratory markers of obesity and insulin resistance.

Low-density lipoprotein size in primary Hypothyroidism : Effects of hormone replacement therapy

Background/Aim: Hypothyroidism is associated with abnormalities in lipid metabolism but its effect on LDL size is not known. This study identified the LDL particle size (pattern ‘A’ or ‘B’) in a group of 50 postmenopausal women with primary hypothyroidism before and after 2 months of hormone replacement therapy (HRT) with the aim of establishing whether hypothyroidism is associated with an increased frequency of pattern B LDL compared with healthy controls, and whether euthyroid recovery modified LDL size. Methods: Lipid parameters (total cholesterol, triglycerides, HDL- and LDL-cholesterol, apoprotein AI and B and lipoprotein(a)) were determined in a blood sample from each patient and control. LDL size was determined by gradient gel electrophoresis. Determinations were done before and after 2 months of HRT (75–150 μg L-tiroxina/daily) in patients and once in controls. Results/Conclusions: No significant difference emerged in pattern B LDL distribution: 16% in patients and 18% in controls (p = NS). After HRT no statistical variations were observed in LDL size. HRT normalized all other lipid parameters except lipoprotein(a). In conclusion, the increased risk of coronary heart disease assumed to be associated with hypothyroidism is not linked with the presence of pattern B LDL, but rather with concomitant metabolic abnormalities.

Cardiovascular risk factors and recommended lipid goals attainment among patients referred in a tertiary care lipid clinic

BACKGROUND Many adults are not at recommended lipid levels and the extent of treatment of dyslipidemia remains poor. We investigated the burden of cardiovascular risk and the distance of lipid fractions from the recommended targets by statin therapy and risk status in patients referred to a tertiary care lipid clinic. METHODS Assessment of cardiovascular risk factors was performed in 1657 patients, mostly dyslipidemics, referred by family physicians to our Lipid Clinic, 393 patients being under statin therapy. The shortfall of lipid fractions from the National Cholesterol Education Program Adult Treatment Panel-III (NCEP ATP-III) recommended goals was evaluated. RESULTS A high prevalence of cardiovascular risk factors was found. LDL cholesterol target was reached by 20% and 45% of untreated and statin treated patients, whereas non-HDL cholesterol target by 13% and 45% of untreated and statin treated patients, respectively. LDL cholesterol was over the goal by 27% in untreated patients and by 25% in statin treated patients. More than 40% and 65% statin treated patients were taking either a low statin dose or statins with low-to-moderate LDL cholesterol lowering efficacy (<30%). A decrease in the proportion of patients at target and greater shortfalls from recommended goals were found from low to high risk categories. CONCLUSION The shortfall in reaching lipid targets, particularly among high risk statin untreated patients, may be partly explained by delayed or even inadequate lipid lowering therapy. Shortfalls in reaching the targets are not necessarily high and might be possibly managed at a primary care level.