Margherita Azzini

Resistance to activated protein C in healthy women taking oral contraceptives.

Summary. Resistance to activated protein C (APC) is at present considered the most frequent laboratory abnormality in patients with deep‐vein thrombosis. An increased risk for venous thrombosis is associated to the use of oral contraceptives (OC).

Increased Membrane Ratios of Metabolite to Precursor Fatty Acid in Essential Hypertension

Desaturase enzymes are responsible for the conversion of essential fatty acids to the longer-chain eicosanoid precursors. These enzymes require zinc as an essential cofactor, and the following ratios-C20:4/C18:2, C20:5/C18:3, and C22:6/C20:5-are considered indexes of their activity. We analyzed these parameters in plasma and erythrocyte membranes of 105 essential hypertensive patients, 20 white coat hypertensive patients, and 100 age-matched normotensive control subjects. Dietary analysis excluded significant quantitative and qualitative differences in fatty acid dietary intake between essential hypertensive patients and normotensive control subjects. Zinc levels and C20:4/C18:2, C20:5/C18:3, and C22:6/ C20:5 ratios were significantly higher in essential hypertensive patients than control subjects, whereas white coat hypertensive patients showed intermediate values for all these parameters. These data provide evidence for an alteration in fatty acid metabolism of essential hypertensive patients, consistent with increased activity of desaturase enzymes. The consequent greater bioavailability of eicosanoid precursors, and in particular of arachidonic acid, could affect several vascular functions and have a bearing on the pathogenesis or complications of hypertension.

Omega-3 polyunsaturated fatty acid supplements and ambulatory blood pressure monitoring parameters in patients with mild essential hypertension

Objective To evaluate the effects of low doses of oM-3 polyunsaturated fatty acids on ambulatory blood pressure monitoring parameters in a group of mild essential hypertensives. Patients We studied 24 consecutive essential hypertensive patients from our outpatient clinic with mild hypertension (diastolic blood pressure ± 105 mmHg), no previous treatment for 4 weeks at least and no other disease. Methods After a 3-month run-in period, the patients entered an intervention phase and were given 3g oM-3 polyunsaturated fatty acids (85% eicosapentaenoic and docosahexaenoic acid concentrate) daily for 4 months; this phase was followed by a 4-month washout period. Ambulatory blood pressure monitoring was performed at the end of each phase; erythrocyte membrane fatty acids were assessed to check compliance. Results After 4 months of treatment, erythrocyte oM-3 polyunsaturated fatty acids significantly increased but average systolic and diastolic blood pressure and the heart rate did not significantly change; no significant variations were recorded in blood pressure or heart rate variability (assessed as blood pressure and heart rate SD) nor in the diurnal blood pressure rhythm. After washout, a significant decrease was observed in erythrocyte oM-3 polyunsaturated fatty acids but the ambulatory blood pressure monitoring parameters were not substantially modified. Conclusions The present data show that low doses of oM-3 polyunsaturated fatty acids as a single treatment are not effective in lowering blood pressure or the heart rate in mild essential hypertensive patients, despite a significant change in fatty acid cell membrane composition. Nor does this treatment seem likely to affect blood pressure variability or the diurnal rhythm.

Resistance to activated protein C, associated with oral contraceptives use; Effect of formulations, duration of assumption, and doses of oestro-progestins

Resistance to activated protein C (APC-R) is at present considered the most frequent laboratory abnormality in patients with deep vein thrombosis. An increased risk for venous thrombosis is associated with the use of oral contraceptives (OCs). We recently described a statistically significant association between APC-R status and oral contraceptives use in a healthy group of women. We re-evaluated 50 healthy women taking low-dose combination OCs in order to consider a possible correlation between the APC sensitivity ratio (APC-SR) and different oral contraceptive formulations. Seven women showed an APC ratio < or = 2 (APC-resistant). Only one of the seven women was found to be heterozygous for Leiden factor V mutation. We observed no significant differences between normally sensitive and APC-resistant women in terms of duration of OC use, amount of estrogenic or progestogenic dose, or type of formulation. We conclude that APC-resistance associated with oral contraceptives use seems to occur only in predisposed subjects (in our results, about 12% of the healthy population).

Impaired zinc and copper status and altered fatty acid cell membrane composition in essential hypertension.

The apparent antagonism between Zinc (Zn) and Copper (Cu) is a well-known phenomenon and has been documented in various chronic diseases. An impairment in Zn and Cu status has been shown in hypertensive animals (1), suggesting a possible relationship with the pathogenesis of hypertension. Zn and Cu are involved in lipid metabolism, and several studies indicated that a major aspect of Zn-Cu interaction may be related to the opposing effects on essential fatty acids (EFA) metabolism or by differential stimulation of the synthesis of prostaglandins (PGs), whose influence on blood pressure (BP) regulation has been widely documented (2). The conversion of C-18 polyunsaturated fatty acids (PUFA) into the longerchain metabolites proceeds through desaturation and elongation steps; desaturation processes are catalyzed by the Δ4-Δ5-Δ6 desaturases, which are the rate-limiting enzymes in the pathway, and whose activities specifically require Zn and Cu (2). Thus, Zn and Cu availability may modulate the balance of PGs precursors. Also, since C-20 and C-22 are the major PUFA found in phospholipids, most of the cellular functions (fluidity, permeability or the ion transport systems activity) are in some way related to their metabolism (3).

RELATIONSHIPS BETWEEN SERUM COPPER CONCENTRATION AND CARDIOVASCULAR RISK FACTORS IN NORMAL SUBJECTS

High serum copper (s-Cu) has been reported as an independent risk factor for cardiovascular disease (CVD) in both case-control (1) and large prospective population studies (2, 3). The mechanisms underlying these associations are largely unclear. In vitro Cu is highly efficient in promoting the oxidation of low-density-lipoprotein (4), which is considered an important step in atherogenesis. A synergistic effect between the pro-oxidant action of Cu and low status of selenium (an antioxidant), leading to atherogenesis via an imbalance of defence against free radicals has been suggested in vivo (5). Also, experimental animal studies suggest a role of Cu in lipid metabolism, particularly in cholesterol (6) and fatty acid metabolism (7). Within the framework of a cross-sectional survey aimed to study the status of several trace elements in a sample of healthy adults (8), we examined the relationships between s-Cu and several, well-known, risk factors for CVD, including plasma lipoproteins and fatty acids, and coagulation factors.