Hypertension in the elderly: Age- and disease-related complications and therapeutic implications

Summary Effective treatment of hypertension in the elderly requires an understanding of both the progressive course of the disease and the impact of aging on the cardiovascular system, including physiological, genetic, lifestyle, and environmental factors. Review of the literature that has attempted to define the impact of an aging process on cardiovascular structure and function reveals a diversity of findings and interpretations. However, in general, normotensive elderly subjects exhibit the heart and vascular characteristics of muted hypertension, including many features of younger hypertensive patients: cardiac hypertrophy, diminution in resting left ventricular early diastolic filling rate, increased arterial stiffness and aortic impedance, diminution in the baroreceptor reflex, a diminished response to catecholamines and diminished renal blood flow, and an increase in peripheral vascular resistance (PVR). Treatment of elderly hypertensives is more challenging because of the greater likelihood of the presence of concomitant diseases, most importantly, coronary and peripheral atherosclerosis, renal dysfunction, and diabetes mellitus. Isolated systolic hypertension (ISH), the most common form of hypertension in the elderly, has also been clearly shown to be an important predictor of cardiovascular morbidity and mortality, including coronary artery disease, congestive heart failure, and stroke. Treatment of ISH has been shown to lower systolic pressure safely and effectively in the elderly. By reducing PVR, and possibly the arterial stiffness, and thus the early reflected pulse waves, vasodilators, including calcium antagonists, may lower these three components of arterial impedance, and hence lower the arterial load on the heart. The cardiac hypertrophy and reduced left ventricular filling rate associated with hypertension in older individuals can also be ameliorated, to some extent, by calcium channel blockers.Proceedings of a symposium held in Atlanta, Georgia on March 2, 1991.     

Hydrolysis of ochratoxin A by the microbial activity of digesta in the gastrointestinal tract of rats

This study established the influence of dietary neomycin sulphate on the rate of hydrolysis of ochratoxin A (OA) by digesta from the intestine, and its effect on the excretion of OA and its hydrolyzed metabolite, alpha ochratoxin (O), in the urine and feces of the rat. The first in vitro study demonstrated that digesta from the cecum and the large intestine were able to hydrolyze OA whereas digesta from the small intestine and stomach had very low hydrolytic activity against this substrate. Homogenates of the liver had no hydrolytic activity. The second in vivo study demonstrated that digesta from the large intestine and cecum of the neomycin treated rats was much less effective (P<0.001) in promoting the hydrolysis of OA than digesta from the control rats. Neomycin when added directly to the in vitro system, however, did not affect the rate at which OA was hydrolyzed. In a third study, OA was administered in vivo to control and neomycin-treated rats. Rats fed the neomycin containing diet compared to those fed the control diet had a higher concentration (P<0.005) of blood OA, and a greater cumulative excretion of OA plus O over the entire 5 day collection period in the feces (P<0.0001) and a corresponding decrease in the cumulative excretion of OA plus O in the urine (P<0.0001). Individually, there was a marked increase in cumulative fecal excretion of OA (P<0.05) and a corresponding decrease in excretion of O (P<0.05). Individual OA and O values in the urine tended to follow an opposite pattern to that seen in the feces but the differences were not significant (P<0.05). Overall, the results demonstrate that an antibiotic such as neomycin when added to the diet greatly reduces the rate of hydrolysis of OA by digesta from the lower sections of the gastrointestinal tract. Neomycin also alters the pattern of excretion of OA and O in the feces and possibly the urine in rats fed OA. These results suggest that intestinal microorganisms affect disposition of OA.     

The neurobiology of sexual function

This article provides a review of the past and current literature on the neurobiology of sexual function. The influence of endocrine, neurotransmitter, and central nervous system influences on male and female sexual function are discussed for sexual desire, arousal, and orgasm or ejaculation stages of sexual responding. Endocrine factors reviewed include the following: androgens, estrogens, progesterone, prolactin, oxytocin, cortisol, and pheromones. Neurotransmitters and neuropeptides discussed include nitric oxide, serotonin, dopamine, epinephrine, norepinephrine, opioids, acetylcholine, histamine, and gamma-aminobutyric acid. Central nervous system influences on sexual function are discussed briefly with reference to brainstem regions, the hypothalamus, and the forebrain.     

A randomized placebo-controlled double-blind trial of lipid-lowering strategies in patients with renal insufficiency: diet modification with or without fenofibrate

BACKGROUND: Renal insufficiency is characterized by lipoprotein abnormalities including elevated triglyceride levels. PATIENTS AND METHODS: The safety and efficacy of micronized fenofibrate as a treatment for dyslipidemia in patients with progressive renal insufficiency was evaluated in a randomized, placebo-controlled double-blind study comparing fenofibrate and dietary modification to dietary modification alone. Patients were evaluated following a 3-month pre-randomization period of dietary counseling. Twenty-eight patients with moderate renal insufficiency and triglyceride levels 2.3 mmol/l or LDL/HDL ratio 5 were randomized to placebo (n = 12) or fenofibrate (n = 16) therapy. Treatment and dietary counseling continued for 6 months. RESULTS: Ten of 16 patients (63%) treated with fenofibrate achieved a 30% reduction in triglyceride levels or LDL/HDL ratio reduction < 5 compared to 2 of 17% in the placebo group (p = 0.015). Triglyceride levels were significantly reduced in the fenofibrate group (-31%) versus placebo (+1.3%, p = 0.003). In compliant patients (n = 25) there was also a significantly greater increase in HDL cholesterol levels in the fenofibrate group (+19.9%) compared to placebo (-4.7%, p = 0.001). Changes in measured creatinine clearance were not significantly different between the groups and there were no serious adverse effects of treatment. CONCLUSION: Fenofibrate therapy combined with dietary modification effectively reduced triglyceride levels in renal insufficiency patients without serious adverse effects.     

High-density lipoprotein subclasses and esterification rate of cholesterol in children: effect of gender and age

Since the development of coronary heart disease (CAD) is affected by a specific pattern of plasma high density lipoprotein (HDL) effects it may be useful to know whether this occurs already in childhood. In this study we evaluated particle size distribution of HDL by gradient gel electrophoresis and the determination of cholesterol esterification rate (FER_HDL) in plasma depleted of apo B lipoproteins in 221 children (108 boys and 113 girls) aged 4 months to 20 years. Total plasma- (TC), low-density lipoprotein- (LDL-C) and HDL- (HDL-C) cholesterol, HDL unesterified cholesterol (HDL-UC) and plasma triglycerides (TG) were also measured. There were no significant gender and age differences with respect to the plasma TC, LDL-TC and TG but concentration of HDL-TC increased with age. Post-pubertal girls had significantly higher relative concentrations of HDL_2b compared to boys (30.4% vs 17.2%), while HDL_3b,c was lower in post-pubertal girls (8.7% vs. 16.5 %). FER_HDL correlated inversely with HDL_2b and positively with HDL_3b,c particles and was significantly higher in boys of the post-pubertal group compared to girls (16.9%/h vs 12.5%/h). While in girls there was a positive correlation between age and HDL-C, HDL-UC and the relative concentration of HDL_2b no significant correlation were observed in boys. In girls the increase in TC showed a significant correlation with a simultaneous increase in HDL-C, HDL-UC and HDL_2b. In boys TC correlated significantly with changes in TG only. When HDL_2b and HDL_3b,c cholesterol levels are calculated from HDL-C concentration and per cent distribution the differences between males and females are further emphasized. These data indicate that HDL particle size distribution is age- and gender-dependent.