Middle-aged Hypertensive Patients Research Articles

Treatment of Hypertension in the Elderly and Its Effect on Stroke

During 1991 and 1992 three major intervention trials were published that dealt with the value of antihypertensive treatment in the elderly. The three studies were the American Systolic Hypertension in the Elderly Program (SHEP), the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) and the British Medical Research Council Trial of Treatment of Hypertension in Older Adults. The three trials all compared active antihypertensive treatment, mainly consisting of diuretics or β-adrenoceptor blocking agents or the two in combination, with placebo. Two of the trials were double-blind (SHEP and STOP) whereas the MRC trial was single-blind. All three were multicenter, prospective and patients were randomized to either of the treatment modalities. One of the trials (SHEP) was specifically designed to evaluate antihypertensive treatment in patients with isolated systolic hypertension. The SHEP, STOP and MRC trials all showed that treatment of hypertension in the elderly reduces the risk of stroke and cardiovascular events. In two of the trials total mortality was also positively affected, and in the STOP-Hypertension trial, which included the oldest patients with the most severe hypertension, total mortality was reduced by 43%. Based on these trials, it is apparent that antihypertensive treatment with low dose thiazides or β-blockers or the two in combination produced highly beneficial results in elderly patients, i.e. a reduction in stroke and other cardiovascular events as well as in total mortality. Special analyses indicate that the cost/benefit aspects of such treatment is at least as positive as in young and middle-aged hypertensive patients. (Hypertens Res 1994; 17 Suppl. I: S47-S50)

General considerations when treating hypertension.

Numerous intervention studies have clearly demonstrated the value of antihypertensive treatment. By lowering diastolic blood pressure 5 to 6mm Hg in middle-aged hypertensive patients, a 42% reduction in stroke morbidity and a 14% reduction in coronary heart disease morbidity can be obtained. Recently published large intervention trials have shown that antihypertensive treatment provides even greater benefits in elderly hypertensive patients. Not only are cardiovascular morbidity and mortality reduced, but, in the 'old elderly', total mortality is reduced when blood pressure is lowered. It is conceivable that even better outcomes will be achieved with newer antihypertensive therapies, such as calcium antagonists and angiotensin converting enzyme inhibitors, and this possibility is being investigated in large prospective intervention trials.

Captopril improves impaired endothelium-dependent vasodilation in hypertensive patients.

Animal studies suggest that some angiotensin converting enzyme inhibitors augment endothelium-dependent vasorelaxation. We aimed to determine if captopril augments endothelium-dependent vasodilation in middle-aged hypertensive patients. By using strain-gauge plethysmography, forearm vasodilation evoked with intra-arterial acetylcholine (4, 8, 16, and 24 micrograms/min) or nitroprusside (0.2, 0.4, 0.8, and 1.2 micrograms/min) was examined before and after captopril administration (25 mg per os). Before captopril, forearm vasodilation with acetylcholine was less in hypertensive patients (n = 12) than in age-matched (n = 7) or young (n = 7) normotensive subjects, but forearm vasodilation with nitroprusside did not differ among the three groups. Captopril improved forearm vasodilation in hypertensive patients (n = 7) with acetylcholine but nitroprusside did not. In contrast, nifedipine (10 mg per os) did not alter forearm vasodilation with acetylcholine or nitroprusside in hypertensive patients (n = 5). The decreases in mean blood pressure caused by captopril and nifedipine in hypertensive subjects were comparable. Captopril did not alter forearm vasodilation with acetylcholine or nitroprusside in young normotensive subjects (n = 7). These results suggest that captopril in hypertensive patients may acutely improve impaired endothelium-dependent forearm vasodilation that does not result from reduction in blood pressure per se.

Baroreceptor Reflex in Elderly Essential Hypertensives: Effect of Chronic Inhibition of Angiotensin Converting Enzyme

Baroreflex function and plasma angiotensin II (Ang II) were examined in five elderly and five young or middle-aged essential hypertensive patients before and after enalapril treatment. Baroreflex sensitivity (BS) during blood pressure (BP) elevation by phenylephrine (PE) but not during BP reduction by sodium nitroprusside (SNP) was significantly attenuated in the elderly compared with the younger group, while plasma Ang II concentration was not different between the two groups. Enalapril treatment reduced BP without significant changes in heart rate and plasma norepinephrine in both groups, suggesting a leftward shift of barofunction curve. It also increased the BS in some cases in each group. However, plasma Ang II was not significantly reduced during enalapril treatment. The changes in BS did not correlate with changes in plasma Ang II. These results suggest that BS may be attenuated with increasing age independent of plasma Ang II and that ACE inhibitor influences the set point of the barofunction curve and BS by different mechanisms.

Essential hypertension and insulin resistance in non‐insulin‐dependent diabetes

A recent study has shown that young, lean, hypertensive subjects are more insulin resistant than corresponding normotensive subjects. Whether this finding can also be demonstrated in the presence of non-insulin-dependent diabetes mellitus (NIDDM) is not known. Therefore, the degree of insulin resistance was studied in 26 middle-aged hypertensive patients with NIDDM (11 men, 15 women) and 14 normotensive patients with NIDDM (eight men, six women) matched for age, metabolic control and the duration of diabetes, utilizing the glucose clamp technique. Non-obese NIDD patients (body mass index less than 27.0 kg m-2) with hypertension (n = 11) had significantly lower glucose disposal rates (GDRs) during the last 60 min of euglycaemic (5.5 mmol l-1) and hyperinsulinaemic (approximately 600 pmol l-1) clamp studies than NIDD patients without hypertension (n = 6) (782 +/- 94 vs. 1418 +/- 97 mumol m-2 min-1, P less than 0.05). In contrast, GDRs were similar in obese NIDD patients with (n = 15) and without (n = 8) hypertension (802 +/- 90 vs. 849 +/- 90 mumol m-2/min-1, respectively, P = NS). Basal hepatic glucose output, suppression of hepatic glucose production during hyperinsulinaemia and insulin secretion capacity did not differ between hypertensive and normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of ketanserin in patients with essential hypertension.

The pharmacokinetics of ketanserin and its main metabolite ketanserin-ol, and the antihypertensive effects of intravenous, single oral and chronic oral (40 mg once daily) administration of ketanserin, have been investigated in a single blind study of 10 patients with uncomplicated mild hypertension. Ketanserin had a terminal half-life of 29.2 h, a plasma clearance of 518 ml/min and a volume of distribution of 18.0 l/kg. Chronic oral intake of 40 mg ketanserin (tablet formulation) gave a peak concentration of unchanged ketanserin of 88 ng/ml after 1.1 h. Its absolute bioavailability was 48%. During chronic therapy the maximal concentration of ketanserin-ol was 208 ng/ml and its half-life of elimination was 35.0 h. As this metabolite can be oxidized back to ketanserin, it contributes to the prolonged half-life of unchanged ketanserin seen during chronic therapy. The blood pressure was reduced by approximately 15% by oral ketanserin. The maximal reduction in blood pressure coincided with the peak concentration of unchanged ketanserin. During chronic therapy with 40 mg once daily blood pressure was reduced over 24 h. The heart rate was slightly reduced and the cardiovascular responses and the plasma noradrenaline concentrations during isometric exercise were only slightly influenced by ketanserin therapy. Thus, unchanged ketanserin has a relatively long half-life during chronic oral therapy and its pharmacokinetics in middle-aged hypertensive patients is similar to that in normal young volunteers.

Hypertension in the Elderly

A review on the effects of ageing on cardiovascular function, with special reference to high blood pressure (BP), is given in this seminar. In most western populations the diastolic and especially the systolic BP increases with age in both sexes and this has been observed both in cross-sectional and longitudinal studies. Over the age of 60 the diastolic BP decreases. Of the different risk factors for cardiovascular diseases, only BP has been shown consistently to be an independent risk indicator in subjects 70 years or older. Hypotensive drugs used in the treatment of middle-aged hypertensive patients can also reduce the BP in elderly hypertensive patients can also reduce the BP in elderly hypertensive patients but are likely to produce more adverse reactions such as electrolyte disturbances and glucose intolerance by thiazides, depression by reserpine, orthostatic hypotension by methyldopa and excessive bradycardia by beta-blockers. A prolongation of life expectancy in hypertensive patients 60 years or older by hypotensive drug therapy has not been shown conclusively in controlled trials.

The effect of near-maximal isometric stress on the presence and amplitude of fourth heart sounds

Near-maximal isometric exercise (IHG) was employed to provoke new, or alter pre-existing fourth heart sounds (S4s) in ambulatory middle-aged normal subjects (N), hypertensive patients (HHD), and patients with coronary disease (CAD). S4 amplitudes and systolic time intervals (STIs) were measured blindly. No subjects without a resting S4 developed a new S4 during IHG. Increases and decreases of pre-existing S4 provoked by IHG were not statistically different among all groups. Among subjects matched for presence of S4, STIs during IHG showed significant shortening of the ejection time index and prolongation of Q-Im in the HHD group only. When the subjects who increased a resting S4 during IHG were compared with the subjects who decreased their resting S4 during IHG there were no significant differences in the responses of STIs. Thus, in these ambulatory, hypertensive patients, coronary patients, and normal subjects, near-maximal IHG did not induce new S4s and had variable effects on pre-existing S4s. Neither type of S4-response could be associated with corresponding changes in systolic time intervals.

Diminished baroreceptor sensitivity in elderly hypertensives Possible role of atherosclerosis

Baroreceptor sensitivity was studied in twelve young normotensive subjects and forty hypertensive patients, separated into two groups according to their age, severity of hypertension and signs of severe atherosclerotic vascular disease. Under stabilized circulatory conditions, the changes of pulse rate in response to changes of blood pressure, attained by infusion of trimethaphan camphorsulfonate alone or with norepinephrine, was examined. There was gradually diminished change of pulse rate in relationship to blood pressure change as age and hypertension advanced. However, although the blood pressure threshold of stimulation was obviously higher in the middle-aged hypertensive subjects than in the normotensive ones, the slightly reduced baroreceptor sensitivity was not significantly different from that in the normotensive group. Only in the elderly hypertensive patients was significantly diminished baroreceptor sensitivity demonstrated, which was also significantly different from that in the middle-aged hypertensive patients. It is speculated that the significantly diminished baroreceptor sensitivity found in the elderly hypertensive patients may be due to atherosclerotic changes in the region of the baroreceptors, although proof of that is not available at the present time.

Slowing of response time in young and middle-aged hypertensive patients.

Reaction time (RT) was compared in 160 hypertensive and 43 normotensive adults. After being screened for coronary and cerebrovascular disorders, each subject completed 12 variations of a serial RT task. Subjects were blocked into normotensive, nonmedicated hypertensive, and medicated hypertensive groups, and into three age groups: 18-31; 32-45; 46-59. Response slowing was observed with increasing age. Significant slowing was also seen in the medicated but not the nonmedicated hypertensive group. Plasma renin activity (PRA) interacted with the medication factor; longest RTs were obtained for treated subjects with low and normal PRA and untreated subjects with high PRA. These results were interpreted in terms of changes in ability to autoregulate cerebral blood flow as a result of vascular damage.

Renal artery disease and hypertension.

The most important cause of renal hypertension is actually an extrarenal disease, occlusive disease of the renal arteries. Arteriosclerosis is responsible for the majority of these lesions, and stenosing fibroplasia accounts for a smaller group. The renal arterial plaques that are now being recognized in middle-aged hypertensive patients have a grave potential in terms of loss of renal function.