Treatment of heterozygous familial hypercholesterolemia: atorvastatin vs simvastatin.

BACKGROUND AND AIM: This study compares the cholesterol-lowering efficacy of atorvastatin and simvastatin in attainment of the National Cholesterol Education Program (NCEP) guidelines LDL-cholesterol (LDL-C) goal in patients with heterozygous familial hypercholesterolemia (HFH). The association of atorvastatin with significant changes of blood fibrinogen and other coagulative variables was also compared with that of simvastatin. METHODS AND RESULTS: In a 24-week study, 26 HFH patients (16 men, 10 women, mean age 55.1 +/- 11.3) were randomly assigned to receive atorvastatin or simvastatin. The initial daily dose of 10 mg was progressively raised to 20, 40 and 80 mg in patients who had not reached the NCEP LDL-C goal. Significant reductions of total and LDL-C (p < 0.001), triglycerides (p < 0.005) and apoB100 (p < 0.001) were observed in both groups. Atorvastatin caused greater reductions in total cholesterol (-42% vs -30%) (p < 0.001) and LDL-C (-50% vs -37%) (p < 0.01). Three patients treated with Atorvastatin (23%) and none of those treated with simvastatin reached the NCEP LDL-C goal at the end of the study. No significant departures from the fibrinogen and coagulative variable baselines were observed. CONCLUSIONS: Atorvastatin has greater cholesterol-lowering efficacy than simvastatin in HFH.

Cholesterol and long-term mortality after acute myocardial infarction in elderly patients.

METHOD: We investigated the association of total serum cholesterol concentrations and subsequent overall and coronary mortality in 304 patients aged > or =65 discharged from hospital after acute myocardial infarction. RESULTS: There was no association between total cholesterol concentrations and mortality due to either coronary heart disease or to all causes in all patients or, separately, in men, women, patients younger than 75 and patients aged 75 years and older.

[In-hospital mortality of elderly patients with myocardial infarct. Difference between the sexes]. / Mortalità intraospedaliera in pazienti anziani con infarto miocardico. Differenze tra i due sessi.

The number of women who become ill and die from acute myocardial infarction (AMI) increases steadily with age. It is not yet clearly defined whether and why women suffer from a higher in-hospital mortality rate after AMI. In this study we evaluated the importance of the female sex as a risk factor for in-hospital mortality in elderly patients suffering from AMI. A retrospective study was performed in 724 patients (429 males, 295 females) aged > or = 65 years (mean age 74.9 +/- 6.3 years) consecutively admitted to San Giovanni Battista Hospital in Turin during the period 1988-1991 with validated primary discharge diagnosis of AMI. In-hospital mortality was significantly higher in females (34.6%) compared to males (25.6%, p > 0.01). After multivariate analysis female sex was not independent predictive for in-hospital death. Multivariate analysis was therefore repeated in the various sections of the history of AMI (anamnestic variables, including age and sex: physical signs on admission, ECG findings, laboratory tests, clinical progress, including complications and treatment) in order to identify the factors responsible for the higher mortality rate in women. These were found to be low hemoglobin values (< 12 g/dl) on admission, development of cardiac failure disorders and rhythm disturbances during hospitalization, and differences in therapeutic procedures. In spite of the absence of an independent unfavourable effect of female sex, elderly women with AMI have a higher in-hospital mortality rate. A more precarious state of health on admission, a peculiar susceptibility to severe complications during hospital-stay and differences in therapeutic procedures appear to be the factors responsible for this increased mortality rate in women.

Correlation between ankle-arm blood pressure index (AAI) and atherosclerotic vascular involvement in coronary arteries.

Several reports indicated that presence of peripheral arterial disease (PAD) and low ankle-arm index (AAI) are independently associated with a substantial increase in cardiovascular mortality, particularly from coronary heart disease (CHD). The goal of the study was to evaluate whether the AAI correlates with extension and severity of the atherosclerotic vascular involvement in coronary arteries. One-hundred and sixty-one male inpatients who consecutively underwent coronary angiography were referred to our Vascular Laboratory for ultrasonographic examination of lower extremity arteries. Coronary artery disease (CAD) was classified by its extent (number of major coronary vessels affected by at least one stenosis of 50% or more) and severity (sum of the maximum percentages of stenosis in each of the major coronary vessels). Differences in AAI and other covariates in relation to extent and severity of CAD were evaluated using univariate and multiple regression analysis. Total cholesterol (p < 0.05) and, inversely, AAI (p < 0.005) were correlated with extent of CAD. Total cholesterol (p < 0.005), LDL-cholesterol (p < 0.05), triglycerides (p < 0.05), diabetes (p < 0.05) and, inversely, AAI (p < 0.005) were correlated with the severity score. After multiple regression analysis including these covariates, AAI was independently and inversely correlated with the extent and severity (for both: p < 0.005) of coronary artery atherosclerotic involvement. The AAI is strongly, independently and inversely correlated with the extent and severity of coronary artery atherosclerosis. We suggest that the determination of the AAI can be of help for identifying patients who are likely to have wide and severe coronary atherosclerosis.

The ankle-arm blood pressure index is strongly predictive for cardiovascular mortality in men.

In recent years some reports suggested that the presence of peripheral arterial disease (PAD) or a decrease in the ankle-arm blood pressure index (AAI) are associated with a substantial increase in cardiovascular mortality. The end-point of the study was to evaluate whether the AAI is an independent predictor of mortality in adult men. Date and cause of death were ascertained for a cohort of 215 male outpatients who underwent ultrasonographic examination of lower extremity circulation in the Noninvasive Vascular Diagnostic Laboratory of our University Department. The study was designed over a 10-year period of observation: total and cardiovascular mortality were considered. An AAI of 0.90 or less was selected as cutpoint for the definition of PAD. The death rates were significantly higher among patients with PAD than in normal subjects. After adjusting for age and other covariates (Cox proportional-hazards models), the baseline AAI was strongly, independently, inversely correlated with all-cause mortality (relative risk = 0.09, 95% confidence interval /CI/ = 0.03-0.3), cardiovascular disease mortality (relative risk = 0.02, 95% CI = 0.001-0.15) and ischemic heart disease mortality (relative risk = 0.03, 95% CI = 0.005-0.24). The independent association did not change after the exclusion of patients with history of previous cardiovascular events at baseline and after excluding patients who survived one year or less since the baseline evaluation. Our results confirm that a decreased AAI is associated with a substantial increase in cardiovascular mortality. Routine evaluation of the AAI could be of help for identifying high risk patients.

[Associations between arterial hypertension and other cardiovascular risk factors in subjects over 65 years of age]. / Associazione tra ipertensione arteriosa ed altri fattori di rischio cardiovascolare in soggetti ultrasessantacinquenni.

The goal of this study was to evaluate whether in subjects aged 65 or over hypertensive patients have a greater prevalence of risk factors than normotensives. 1369 subjects, aged 65 or over, have been retrospectively investigated. The following risk factors were considered: cigarette smoking, left ventricular hypertrophy, diabetes mellitus and atrial fibrillation (analyzed as dichotomous variables), B.M.I., blood concentration of total, -LDL-HDL cholesterol, triglycerides and total/HDL cholesterol ratio (analyzed as continuous variables). The mean number of risk factors was calculated in hypertensive and normotensive subjects; the association between hypertension and risk factors was evaluated using univariate and multiple logistic regression analysis. 451 subjects (32.9%) were found to be hypertensives. The average number of risk factors was significantly greater in hypertensive than in normotensive subjects (1.85 +/- 1.27 vs 1.39 +/- 1.15, p < 0.001), and, in both groups, in men than in women. Left ventricular hypertrophy (p < 0.001), total cholesterol (p < 0.001), diabetes mellitus (p < 0.001) and atrial fibrillation (p < 0.01) were found to be independently associated with the presence of hypertension. We concluded that among the elderly there is a greater prevalence of risk factors in hypertensive than in normotensive subjects and that some risk factors--left ventricular hypertrophy, atrial fibrillation, diabetes mellitus, and blood levels of atherogenic lipids--are independently associated with the presence of hypertension.

Risk factors for atherosclerosis and aging.

In order to investigate the association between atherosclerosis and risk factors in aged subjects, Doppler ultrasound scans were used to identify the presence and severity of carotid and femoral atherosclerosis in a sample of 457 community living subjects (mean age 55.4 +/- 18.7 years) of the metropolitan area; the ultrasonographic findings were then related to primary cardiovascular risk factors. Carotid and femoral plaques were found respectively in 178 (38.5%) and in 180 (39.4%) subjects. Prevalence of atherosclerosis, number of plaques and percentage of stenosis have been observed to increase with age. All the main cardiovascular risk factors (age, male sex, hypertension, cigarette smoking, diabetes and hypercholesterolemia) resulted significantly associated with both carotid and femoral atherosclerosis in the total series and, more strongly, in subjects aged under 65. On the contrary, most of these associations disappeared in subjects aged 65 or more. Multiple logistic regression analysis confirmed that in this age group only age and male sex were independently associated with carotid and femoral atherosclerosis; of the other risk factors cigarette smoking alone was an independent risk factor for femoral atherosclerosis. We conclude that in the elderly, in spite of the age-related increase in carotid and femoral atherosclerosis, the association between risk factors and atherosclerotic disease is less relevant than at younger ages.

[Ischemic stroke and transient ischemic attacks: a case-control study of the risk factors in elderly hospitalized patients]. / Stroke ischemico e attacchi ischemici transitori: studio caso-controllo sui fattori di rischio in pazienti anziani ospedalizzati.

We have evaluated in a case-control study the association of the main risk factors with cerebrovascular ischemic accidents in elderly patients. Two hundred and twenty patients aged 65 year or more (average age 77.3 +/- 7.3 yr, 93 males and 127 females) admitted to our Division for stroke (122) or transient ischemic attacks (TIA) (98) were enrolled: 220 hospitalized patients, age and sex-matched, without actual or previous cardiovascular clinical manifestations were the control group. Advanced senile decay, hepatic or renale failure and malignancies were considered exclusion criteria for both groups. The following risk factors have been considered: family history, obesity, cigarette smoking, diabetes, hypercholesterolemia, hypertriglyceridemia, atrial fibrillation, left ventricular hypertrophy, and related continuous variables. After logistic multiple regression analysis, atrial fibrillation, hypertension and blood cholesterol concentration above 240 mg/dl were significantly and independently associated with stroke, while only hypertension and hypercholesterolemia were associated with TIA. The unexpected finding of a significant association between hypercholesterolemia and cerebrovascular ischemia seems attributable to the choice of hospitalized patients as control group. These results indicate that hypertension and atrial fibrillation are independently associated with ischemic stroke even in advanced age.

A four year clinical and echographic follow-up of asymptomatic carotid plaque.

Eighty-five patients with asymptomatic carotid plaque--a diagnosis revealed by B-mode high-resolution echotomography--were followed up for four years; the echoplaque changes were compared with the clinical history. Eight patients died (2 from stroke, 4 from myocardial infarction, and 2 from lung tumor) and were excluded from the follow-up. Three patients underwent carotid thromboendarterectomy (TEA) (1 bilateral), and these 4 carotids were not considered in the total series. At the first echo Doppler evaluation of 150 carotids, plaques were observed in 112; 38 vessels were free of lesions. Of the 150 carotids, 8 revealed a new plaques. In regard to the echogenic pattern, 95 of the 112 plaques (84.8%) remained unchanged, 16 (14.3%) progressed, and regression of a small homogeneous plaque was observed in 1 patient (0.9%). An increase of the degree of vascular stenosis, was observed in 23 of the 150 carotids (15.3%). Cerebral ischemic symptoms occurred in 5 patients. In 1 patient who suffered from stroke, a new, soft, dyshomogeneous plaque in the carotid of the side of the lesion was observed. In 3 patients (2 with strokes, 1 with transient ischemic attack) the occlusion of a previous severe stenosis was observed. The fifth patient had a stroke on the side of an unchanged, ulcerated hemodynamic lesion. A valid criterion for identifying a risky plaque should be the joint evaluation of the echostructural characteristics and the degree of stenosis.

[Treatment of hypercholesterolemic patients of different age with simvastatin: 1-year study]. / Trattamento di pazienti ipercolesterolemici di diversa età con simvastatina. Studio di un anno.

Nowadays there is no direct evidence that lowering cholesterol may reduce the CHD in the elderly; however, several evidences suggest the potential benefit of a dietetic and/or pharmacologic intervention in healthy young-old hypercholesterolemics. In this study we evaluated the efficacy and tolerability of simvastatin, alone or in combination with cholestyramine, in two groups of patients (group A: age 30-55 years and group B: age 60-75 years) with primary hypercholesterolemia, over a 48-week period. In both groups Simvastatin induced a significant reduction in total and LDL cholesterol (p less than 0.001 both), with a decrease of the total/HDL cholesterol ratio (p less than 0.001). A reduction of the apo-B100 levels was also observed (respectively p less than 0.01 and p less than 0.001) with a significant improvement of the apo-B100/apo-A1 ratio (p less than 0.01). Simvastatin was well tolerated and free of remarkable side effects in both groups.