Forty-two elderly patients (mean age, 66.2 +/- 5.1 yr) with hypertension, treated for an average of 17.3 years (standard deviation, 10.3), and 42 control subjects (mean age, 66.5 +/- 4.8 yr), matched for age, sex, and level of education, were studied with regard to the detection of lesions in the cerebral white matter with magnetic resonance imaging (MRI), particularly with axial T2-weighted images. The assessment of the MRI scans was blinded. Ten hypertensive patients showed confluent lesions in the white matter, versus only 1 control subject (Chi-square test, p = 0.01). The presence of diffuse lesions of the white matter was related to age but not to the known duration of hypertension, nor to the presence of any other cardiovascular risk factors. Cognitive function was measured in 34 hypertensive patients and in 18 control subjects. Results of the Mini-Mental State Examination, the Stroop color-word test, Trailmaking test, and the visual subtest of the Wechsler Memory Scale were worse in patients with confluent lesions of the white matter; there was no difference in mental functioning between hypertensive patients and control subjects with normal white matter or with only small focal lesions. Our findings suggest that long-standing hypertension in some patients may cause not only strokes but also chronic end-organ damage of the brain in the form of demyelination of the white matter, with cognitive decline.

Hypertension in the elderly is associated with white matter lesions and cognitive decline.

A meta-analysis of 295 relevant effect sizes obtained from 25,469 participants confirmed expectations that elevated blood pressure (BP) and essential hypertension (EH) would be associated with lower affect expression but with more negative affectivity and defensiveness. The strongest associations occurred for defensiveness and measures of anger and affect expression linked to an interpersonal context(s). However, a number of other factors also were found to moderate associations of BP with personality measures, including awareness of BP status, gender, occupation, and diastolic versus systolic BP assessment. Given these moderators, the authors conclude that a traditional view of personality causing EH is untenable and that, not incorporating multifactorial, synergistic approaches is likely to obscure associations of personality-behavior with EH.

Elevated blood pressure and personality: a meta-analytic review.

Doxazosin is a long-acting alpha 1-adrenoceptor antagonist structurally related to prazosin and terazosin. Its antihypertensive effect is produced by a reduction in the smooth muscle tone of peripheral vascular beds resulting in a decrease in total peripheral resistance without significant effect on cardiac output or heart rate. In benign prostatic hyperplasia, doxazosin's effect of relieving bladder outflow obstruction is produced through a reduction in prostatic tone mediated via alpha 1-adrenoceptor blockade. In most comparative trials doxazosin has proven to be equally effective as the comparator drug in the treatment of mild to moderate hypertension. It has been used in a variety of patient populations including the elderly, Blacks, smokers, and patients with concomitant disease states such as renal dysfunction, hypercholesterolaemia, non-insulin dependent diabetes mellitus (NIDDM) and respiratory disease. Doxazosin has also been used successfully in combination with beta-adrenoceptor antagonists, diuretics, calcium channel antagonists, and angiotensin-converting enzyme inhibitors in patients with hypertension that is uncontrolled with monotherapy. Doxazosin has a beneficial effect on some of the risk factors associated with coronary heart disease including elevated serum lipid levels, impaired glucose metabolism, insulin resistance and left ventricular hypertrophy. Modest decreases in total cholesterol, low density lipoprotein cholesterol and triglycerides are seen with doxazosin therapy while small increases in high density lipoprotein cholesterol and the high density lipoprotein cholesterol/total cholesterol ratio are consistently reported. Some studies have reported an improvement in glucose tolerance although this effect has been more consistently seen in nondiabetic patients than in patients with NIDDM. Additionally, doxazosin produces a similar reduction in left ventricular hypertrophy to other antihypertensive agents. Modelling-based calculations suggest that doxazosin significantly reduces the risk of developing coronary heart disease in patients with mild to moderate hypertension, although this remains to be confirmed in long term prospective studies. Doxazosin appears to be a promising agent in the treatment of urinary symptoms associated with benign prostatic hyperplasia. Similar to other alpha 1-adrenoceptor antagonists, doxazosin treatment produces increases in peak and mean urinary flow rates and improves other objective and symptomatic measures.(ABSTRACT TRUNCATED AT 400 WORDS)

https://link.springer.com/content/pdf/10.1007/BF03259147.pdf

Doxazosin. An update of its clinical pharmacology and therapeutic applications in hypertension and benign prostatic hyperplasia.

Papers pp 671, 676, 677 General practice pp 680, 686, 690 Education and debate pp 702, 705, 709

Ten years ago clinical recommendations on preventing cardiovascular disease focused primarily on managing individual risk factors, particularly raised blood pressure and cholesterol concentrations. Typically, separate guidelines were developed for each risk factor and treatment was recommended when that factor was above a specified level1 The recommendations were informed mainly by evidence from cohort studies showing increased relative risks of cardiovascular disease in people with raised levels of the risk factor2 and by evidence from randomised controlled trials showing relative benefits from lowering the factor.3 4

Over the past decade we have witnessed a remarkable change from these recommendations based on relative risk to ones based on absolute risk—that is, incidence. If Geoffrey Rose, arguably the most influential cardiovascular disease epidemiologist ever, was living today, he would support this revolution, which echoes his 1991 advice that “All policy decisions should be based on absolute measures of risk; relative risk is strictly for researchers only.”5 This week's BMJ brings together a range of papers relevant to this paradigm shift in cardiovascular risk management.

One of the most recent examples of guidelines based on absolute risk is the Joint British Recommendations on the Prevention of Coronary Heart Disease in Clinical Practice, published late last year6 and summarised in this issue (p 705).7 Taking the lead from the European societies of cardiology, atherosclerosis, and hypertension, which jointly published coronary heart disease prevention guidelines in 1998, 8 the British Cardiac Society, British Hyperlipidaemia Association, and British Hypertension Society joined forces to develop the current British recommendations. These new clinical guidelines recommend that priority for treatment should be given to patients at high absolute risk …

https://www.bmj.com/content/bmj/320/7236/659.full.pdf

Guidelines on preventing cardiovascular disease in clinical practice.

Objective

To compare the antihypertensive efficacy of a new angiotensin II antagonist, valsartan, with a reference therapy, amlodipine.



Methods

One hundred sixty-eight adult outpatients with mild to moderate hypertension were randomly allocated in double-blind fashion and equal number to receive 80 mg valsartan or 5 mg amlodipine for 12 weeks. After 8 weeks of therapy, in patients whose blood pressure remained uncontrolled, 5 mg amlodipine was added to the initial therapy. Patients were assessed at 4, 8, and 12 weeks. The primary efficacy variable was change from baseline in mean sitting diastolic blood pressure at 8 weeks. Secondary variables included change in sitting systolic blood pressure and responder rates.



Results

Both valsartan and amlodipine were effective at lowering blood pressure at 4, 8, and 12 weeks. Similar decreases were observed in both groups, with no statistically significant differences between the groups for any variable analyzed. For the primary variable the difference was 0.5 mm Hg in favor of valsartan (p = 0.68; 95% confidence interval, −2.7 to 1.7). Responder rates at 8 weeks were 66.7% for valsartan and 60.2% for amlodipine (p = 0.39). Both treatments were well tolerated. The incidence of drug-related dependent edema was somewhat higher in the amlodipine group, particularly at a dose of 10 mg per day (2.4% for 80 mg valsartan; 3.6% for 5 mg amlodipine; 0% for valsartan plus 5 mg amlodipine; 14.3% for 10 mg amlodipine).



Conclusions

The data show that valsartan is at least as effective as amlodipine in the treatment of mild to moderate hypertension. The results also show valsartan to be well tolerated and suggest that it is not associated with side effects characteristic of this comparator class, dihydropyridine calcium antagonists.



Clinical Pharmacology & Therapeutics (1996) 60, 341–346; doi:

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: A comparative study of the efficacy and safety against amlodipine

The present guidelines were prepared by a subcommittee of the WHO/ISH (International Society of Hypertension) Mild Hypertension Liaison Committee, and wee finalized after discussion at the Fifth WHO/ISH Mild Hypertension Conference. They include the definition of mild hypertension, and describe blood pressure measurement, factors influencing the decision to begin treatment, methods of treatment, and follow-up. These guidelines are a revision of those published in 1986; they are based on the best available scientific evidence, and will be updated in the future to keep abreast of further developments in this field.

A. E. Doyle

Papers

1989 Guidelines for the management of mild hypertension: Memorandum from a WHO/ISH meeting