Haemorheological and endothelial-dependent alterations in heart failure after ACE inhibitor, calcium antagonist and beta blocker.

The aim of our study was to evaluate endothelium-dependent dilatation induced by an ACE-inhibitor, calcium antagonist and beta blocker in patients suffering from heart failure (NYHA class II and III). We studied 34 patients (19M, 15F, mean age 76.96+/-8.82) in pharmacological wash-out for at least one week, divided into 3 groups: Group A (15 patients, 9M and 6F) taking ramipril (5 mg/die); Group B (10 patients, 6M and 4F) taking amlodipine (10 mg/die), Group C: (9 patients, 4M and 5F) taking carvedilole (25 mg/die). The groups were homologous for NYHA class and instrumental echographic parameters (mean EF=22.5+/-6.7 and mean sAPP 38.4+/-8.7). At the beginning and after 3 weeks of therapy, we performed a clinical and instrumental assessment; we studied endothelial function by determination of L-arginine and L-citrulline (amino acids of the nitric oxide metabolic pathway), the L-citrulline/L-arginine ratio (an index of NOS activity) and VCAM-1 (endothelial dysfunction index); haemorheological parameters (blood viscosity, plasma fibrinogen and erythrocyte morphology); coagulative/fibrinolytic parameters (PT, aPTT, fibrinogen and PAI-1). The results show that L-citrulline and L-arginine increase, while VCAM-1 decreases. The L-citrulline/L-arginine ratio increases in a statistically significant way. This trend is maintained in each group. These results demonstrate that the drugs used induce an improvement of endothelium-dependent dilatation. In addition, there is progressive haemorheological and fibrinolytic improvement, with a reduction of PAI-1 and blood viscosity.

[Is there a relationship between sex, age, Lp(a) blood levels, lipid values, and atherosclerotic carotid lesions?]. / Esiste una relazione tra sesso, età, concentrazione ematica della Lp(a), valori del quadro lipidico e lesioni carotidee aterosclerotiche?

Recently many studies have been leaded out to identify the risk factors for development of atherosclerosis in cerebral vessels. To value the relationship between lipidic parameters with lipoprotein(a) and the degree of atherosclerotic stenosis of carotids, we have examined with colorsonographic assay the carotid vessels in a sample of 292 patients (171 men, 117 women, average age 71 years, DS +/- 12); we have measured the concentration of lipidic parameters [total cholesterol, HDL cholesterol, LDL cholesterol, Apo A, Apo B100, triglycerides and Lp(a)]. HDL Cholesterol showed an inverse relationship to carotid atherosclerosis: that relationship was not statistically significant. Men had much more atherosclerosis than women (p < 0.05) and the degree of stenosis was related to age (p < 0.01). Only in patients under 70 years old, total cholesterol concentration showed a positive association with the size of the atherosclerotic plaques. Lp(a) was neither associated with the degree of carotid atherosclerotic stenosis in all patients of our sample or when selected for age.

The association of serum lipoprotein(a) levels with myocardial infarction and ictus cerebri in the elderly.

This study was aimed at revealing the relationship between the serum concentrations of lipoprotein(a) [Lp(a)], the coronary atherosclerotic disease (CAD) and the cerebral vasculopathies (CVP) in elderly patients. A group of 117 patients (66 women and 51 men, mean age 83 +/- 5.8 years) was investigated. Of them, 58 suffered from acute myocardial infarct (AMI) and 59 from ictus cerebri (IC). The parameters were compared with those obtained from a control-group of 88 old people without any recent clinical history of cerebrovasculopathy or atherosclerotic coronariopathy. In the patients with AMI, the average serum value of Lp(a) was 40.8 +/- 18.5 mg%, and in those suffering from IC, it was 46.7 +/- 13.2 mg%; the differences of these averages against the mean found in the control patients (23.2 +/- 11.5 mg%) were statistically significant (p < 0.01). One can conclude that an increased Lp(a) is of diagnostic value for the presence of both IC and AMI, and represents a risk factor for cerebrovasculopathies, too.

[An epidemiological study on blood viscosity and intraerythrocytic calcium in a group of high-school students selected according to their family histories]. / Indagine epidemiologica sulla viscosità ematica e sul calcio intraeritrocitario in un gruppo di studenti liceali selezionati in base all'anamnesi familiare.

An epidemiological study was performed in a group of secondary school students selected according to their family history to assess whether changes exist in blood viscosity and intraerythrocytic calcium levels in young healthy subjects with positive family histories of arterial hypertension or cerebral and cardiac ischemic vasculopathies, compared to a control group with a negative family history of these disorders. A population of 130 secondary school students without any pathologies were subdivided into 4 groups: 1) with a positive family history of ischemic cardiopathy (ICP); with a positive family history of cerebral ictus; 3) with a family history of arterial hypertension; 4) a negative family history of these diseases. Total blood viscosity, hematocrit, plasma fibrinogen and intraerythrocytic calcium was evaluated in all groups. The results show that these parameters were within the normal range, as was to be expected in healthy subjects. Blood viscosity was also normal in all groups; intraerythrocytic calcium levels were slightly higher in groups with histories of cardiovascular disease and in particular there was an increased percentage of cases with values above the threshold level. Higher fibrinogen levels were also recorded, but always within the normal range, in the group with a positive history of ICP. The epidemiological study is important to assess whether a family pattern of cardiovascular disease can also influence such independent risk parameters as blood viscosity and intraerythrocyte calcium, owing to the possible greater frequency of development of cardiovascular disease.

[Plasma Lp(a) levels: a comparison between diabetic and nondiabetic patients with the nephrotic syndrome and control subjects]. / Livelli plasmatici di Lp(a): confronto tra pazienti diabetici, non diabetici, affetti da sindrome nefrosica e soggetti di controllo.

The aim of this study was to evaluate Lp(a), total, HDL and LDL cholesterol, triglycerides, Apo A and Apo B100 plasmatic concentrations in patients affected by nephrotic syndrome that is known able to increase the ratio of the risk of cerebral and cardiovascular events, in comparison with a group of healthy patients homologous for sex and age. In the group of patients with nephrotic syndrome we have compared the variables between diabetic mellitus type I patients and non diabetic patients. All the variables, in exception of HDL cholesterol, were significantly increased in the group of patients with nephrotic syndrome compared with the control group. HDL-cholesterol concentration was significantly higher in controls than in nephrotic patients. Diabetic and nephrotic patients showed increased levels of Lp(a) concentration than non diabetic patients and the difference was statistically confirmed. These data suggest that Lp(a) acts really like a risk factor for atherosclerotic disease, being elevated in patients characterized for increased risk for cerebral and cardiovascular events because of the presence of nephrotic syndrome. Moreover we can suppose that elevated plasmatic Lp(a) levels in nephrotic patients could be linked to increased synthesis of proteins in the liver as physiological reaction to severe proteinuria.

[Lp(a) and lipid order in a group of secondary school students selected according to their family anamnesis]. / Lp(a) e quadro lipidico in un gruppo di studenti liceali selezionati in base all'anamnesi familiare.

In this study we evaluated the several risk-factors, Lp(a) and lipids order, related to the family history for ischaemic cardiovascular disease (CHD) atherosclerotic cerebrovasculopathy and arterious hypertension, in a healthy adolescent group, to stress possible early and significant alteration of the lipids order and Lp(a); we also considered which of these parameters may be considered the risk factor most closely related to family history. We studies 130 healty high school students, mean age 16.5 +/- 5.5 years, selected in four groups related to the family history: the first one composed of 34 subjects with positive family history for CHD; the second one of 32 subjects with positive family history for cerebral infarction (CI); the third by 32 subjects with family history for arterial hypertension and the last group by 30 control subjects. Mean value of all variables considered was in the normality range. Lp(a) resulted in the normality range with the exception of the group with positive family history for CHD. Also the traditional risk factors (Total-Col., LDL/Col. and Triglycerides) were increased in this group. Besides the differences between the mean of Lp(a) and Total/Col. in the group with positive family history for CHD and in the control group were statistically significant. The results showed that Lp(a), even if it cannot replace the family history in the screening of coronary atherosclerotic disease, might be considered a risk marker of early atherosclerotic disease.

[Lipoprotein(a): structure, metabolism and atherosclerotic disease]. / La lipoproteina(a): struttura, metabolismo e malattia aterosclerotica.

Lipoprotein(a) was discovered by chance by Berg in 1963; after twenty years of research, the chemical, physical and metabolic characteristics of Lp(a) are now known. This lipoprotein forms the missing link between the lipid metabolism and the coagulation-fibrinolysis process. The A. describe its similarity to plasminogen, its capacity to delay coagulum or embolus destruction and highlight its structural and functional similarity to lipid metabolism. To day, a total of 6 Lp(a) isoforms have been identified with different molecular weights: in addition, the inverse proportion between the isoforms' molecular weight and Lp(a) plasma concentration has been demonstrated. Lp(a) is not the product of the metabolism of other lipoproteins nor is it a catabolite of LDL; it is produced ex-novo and does not apparently exchange its proteic fraction with other lipoproteins. The paper also examines the question of whether Lp(a) is a plasma marker which increases during the formation of atherosclerotic plaque or whether it should not be considered an atherogenetic factor. To this end the possible mechanisms by which Lp(a) is deposited in plaque are examined. Lastly, the paper reviews all studies concerning the relationship between Lp(a), ischemic cardiopathy and cerebrovascular disease.

[Therapeutic effects of nicofibrate on diabetic hyperlipemia]. / Effetti terapeutici del nicofibrate sull'iperlipemia diabetica

The plasma lipid picture before, during and after 4 months of administering p-chloro-phenoxy-alpha-isobutyrrate of 3-hydroxy-methylpyridine hydrochloride (Nicofibrate) in a group of diabetics was studied. Treatment led to a significant reduction in plasma cholesterol and triglycerides and brought the lipoprotein picture back within the norm. Nicofibrate did not lead to significant increases in uricaemia nor to any worsening in carbohydrate tolerance. At the doses used, a significant drop in plasma prothrombinic activity was encountered, while no noteworthy variations were observed in the other biohumoral parameters examined. In the light of these results, the various aetiopathogenetic aspects of the hyperlipaemia so frequently observed in diabetes mellitus are discussed.