Comparative effects of aging in men and women on the properties of the arterial tree.

OBJECTIVES: We measured the properties of the arterial tree, seeking differences between men and women as they aged. BACKGROUND: There are many differences between men and women, besides menopause, which might account for such disparities. These include body height, heart rate, stroke volume and smaller arterial diameters. Any gender differences in arterial stiffness could influence pulse pressure (PP), now recognized as a cardiovascular risk factor. METHODS: A total of 530 patients (347 men and 183 women) were classified by age into quartiles: < or = 40, 41-47, 48-54 and > or = 55 years. The middle groups represented the menopausal years. Studies included brachial artery blood pressure (BP), aortic pulse wave velocity (PWV), B-mode ultrasonography and wave form analysis of the common carotid artery (CCA), with its conversion to the aortic wave formin. Standard echocardiography provided left ventricular dimensions and flows. Calculated values included CCA compliance and distensibility, systemic compliance, stroke volume and peripheral resistance. RESULTS: At all ages, women had higher heart rates but lower BP than men. Pulse pressure, however, was lower in young women and higher in older women. Measurements influenced by body size, such as CCA diameter, compliance and systemic compliance, were lower in women. Those related to arterial wall properties, such as CCA and aortic distensibility, were the same. Although aortic PWV rose similarly with aging, PWV had more of an influence on PP in women than did mean BP. The reverse was true in men. CONCLUSIONS: Despite lower mean BP and similar arterial distensibilitvy, women develop a higher degree of pulsatility with aging, as compared with men. This is mainly due to their smaller physical characteristics, independent of the role of menopause and its related hormonal changes.

Brain expression of presenilins in sporadic and early-onset, familial Alzheimer's disease.

BACKGROUND: Mutations in the presenilin proteins cause early-onset, familial Alzheimer's disease (FAD). MATERIALS AND METHODS: We characterized the cellular localization and endoproteolysis of presenilin 2 (PS2) and presenilin 1 (PS1) in brains from 25 individuals with presenilin-mutations causing FAD, as well as neurologically normal individuals and individuals with sporadic Alzheimer's disease (AD). RESULTS: Amino-terminal antibodies to both presenilins predominantly decorated large neurons. Regional differences between the broad distributions of the two presenilins were greatest in the cerebellum, where most Purkinje cells showed high levels of only PS2 immunoreactivity. PS2 endoproteolysis in brain yielded multiple amino-terminal fragments similar in size to the PS1 amino-terminal fragments detected in brain. In addition, two different PS2 amino-terminal antibodies also detected a prominent 42 kDa band that may represent a novel PS2 form in human brain. Similar to PS1 findings, neither amino-terminal nor antiloop PS2 antibodies revealed substantial full-length PS2 in brain. Immunocytochemical examination of brains from individuals with the N141I PS2 mutation or eight different PS1 mutations, spanning the molecule from the second transmembrane domain to the large cytoplasmic loop domain, revealed immunodecoration of no senile plaques and only neurofibrillary tangles in the M139I PS1 mutation stained with PS1 antibodies. CONCLUSIONS: Overall presenilin expression and the relative abundance of full-length and amino-terminal fragments in presenilin FAD cases were similar to control cases and sporadic AD cases. Thus, accumulation of full-length protein or other gross mismetabolism of neither PS2 nor PS1 is a consequence of the FAD mutations examined.

Changes in arterial structure and function under trandolapril-verapamil combination in hypertension.

BACKGROUND AND PURPOSE: Converting enzyme inhibition and calcium blockade alter large arteries in hypertension. However, the heterogeneity of the response according to the site of cardiovascular measurements has never been investigated. METHODS: In a double-blind study, we compared for 180 days 3 hypertensive patient groups treated with verapamil, trandolapril, or their combination. Using echo-Doppler technique and applanation tonometry, we independently measured mean pressure, local pulse pressure, arterial diameter, and distensibility at 3 arterial sites (brachial and common carotid arteries and abdominal aorta), as well as cardiac and carotid wall structure. RESULTS: Mean and pulse pressure decreased significantly to a greater extent with the drug combination. Regarding arterial and cardiac hemodynamics, significant and similar changes were noted in the 3 groups: decreases in abdominal aorta and carotid but not brachial diameter; increases in carotid artery, abdominal aorta, and brachial distensibility even after adjustment to mean blood pressure reduction; and more substantial regression of cardiac mass than carotid wall thickness. CONCLUSIONS: This study shows that both compounds and more significantly combination therapy decreased mean and pulse pressures measured independently and that the changes in diameter, thickness, and stiffness were influenced primarily by the site of cardiovascular measurements, resulting in a predominant increase in distensibility of muscular arteries, little change in carotid wall thickness, but a significant regression of cardiac hypertrophy.

Enalapril in the treatment of mild-to-moderate heart failure in general medical practice: a prospective and multicentre study concerning 17,546 patients.

The objective of this study was to test the efficacy and tolerability of a precise dosage regimen of enalapril in general medical practice, in combination with conventional therapy, in patients with mild-to-moderate (NYHA classes II and III) congestive heart failure (CHF). 17,546 patients were prospectively included in this multicentre study. After three months of treatment with enalapril, 53.9% of patients were asymptomatic (NYHA Class I) and 75.1% of patients improved by at least one class in the NYHA classification. 64.6% of patients reached maintenance dosage of 20 mg/day of enalapril and mean daily dosage for all patients was 16 mg. Outcome of functional symptoms according to NYHA class was more favourable with maintenance dosages of 15 and 20 mg/day of enalapril than with maintenance dosages of 5 and 10 mg/day of enalapril. Clinical and laboratory safety was good with low rates observed of the main adverse events: cough (1.74%), hypotension (0.34%), postular hypotension (0.30%), dizziness (0.31%) and hyperkaliema (0.13%); 1.4% of patients dropped out of the study because of such events. This extensive and open study confirms, in general medical practice, the feasibility, efficacy and tolerability of a dosage regimen of enalapril, which has been previously determined in controlled studies performed in specialized medical centres, for treatment of mild-to-moderate heart failure.