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Biomedical subjects

A F Lever

Publications and source records attributed to A F Lever.

At least 73 records · Page 4Linked to original sources
PubMed1988

Does therapeutic reduction of diastolic blood pressure cause death from coronary heart disease?

Mortality data from 3350 patients who attended the Glasgow Blood Pressure Clinic between 1968 and the end of 1982 were used to examine the hypothesis that lowering diastolic blood pressure (DBP) below 85 mmHg causes death from coronary heart disease (CHD). Analysis of 257 coronary deaths in quintiles of treated DBP showed a significantly nonlinear relation, with the lowest mortality from CHD occurring in the middle quintile (91-98 mmHg). This finding persisted after adjustment for risk at entry, and was independent of sex and pre-existing CHD. In contrast, the relations between treated systolic blood pressure and death from CHD, and treated DBP and death from stroke were linear. For 2355 patients who were untreated at referral there was no relation between the change in DBP during treatment and death from CHD. In our view, however, these findings do not necessarily support the hypothesis that lowering of DBP below 85 mmHg with treatment causes death from CHD. Evidence for this is indirect and inconsistent, and should not, at present, be used as a basis for any change in treatment practice.

Antihypertensive Agents↗
PubMed1988

High blood pressure in the Western Isles: a comparative study with Dundee.

A screening programme for cardiovascular risk factors in men aged 50-59 was undertaken in North Uist, and the results compared with an age- and sex-matched control group from Dundee screened as part of the Scottish Heart Health Study. Blood pressure levels were higher in the Islanders than in controls (148 +/- 20/89 +/- 10 mmHg vs 134 +/- 19/84 +/- 11 mmHg (P less than 0.001). Analysis of standard twelve-lead electrocardiograms revealed a greater prevalence of left ventricular hypertrophy in the Islanders (51% vs 16%, P less than 0.005), suggesting that the recorded BP differences were real and not artefacts of measurement. The explanation for the higher BP on North Uist is less clear. Environmental factors that might influence BP including body mass index, the amount of exercise taken, alcohol consumption, dietary salt and potassium intake were similar in North Uist and Dundee. By contrast, an analysis of family names in the two centres indicated a greater degree of common ancestry in North Uist (28 surnames/84 islanders v 98 surnames/110 controls, P less than 0.001). These results suggest that known environmental causes of hypertension are not responsible for higher BP amongst men of North Uist, and this with the data on family names raises the possibility that genetic factors are more important.

Electrocardiography↗
PubMed1987

Malignant hypertension in women of childbearing age and its relation to the contraceptive pill.

Eleven of 34 women aged 15-44 with malignant phase hypertension were taking oral contraceptives at presentation. All had had normal blood pressure before starting to take the pill. In four the interval between the start of oral contraception and the diagnosis of malignant hypertension was less than four months, and in eight no other cause for the hypertension was found. Underlying renal disease and renal failure were less common among pill users than among non-users with malignant hypertension who were of similar age. No pill user became normotensive after withdrawal of the pill, but blood pressure was well controlled (diastolic less than 90 mm Hg) in three patients taking only one drug. By contrast, all 23 non-users needed two or more antihypertensive drugs to control blood pressure. Ten year survival was 90% among pill users and 50% among non-users. These results suggest that oral contraceptives may be a common cause of malignant hypertension in women of child-bearing age. If the pill is stopped and underlying renal disease excluded the long term prognosis for such patients is excellent.

Adult↗
PubMed1987

Dietary sodium deprivation raises blood pressure in the rat but does not produce irreversible hyperaldosteronism.

It is reported that dietary deprivation of sodium in young rats produces changes of sodium balance and aldosterone excretion which persist when normal sodium intake is restored. To test this further, sodium intake was reduced 10-fold in rats. In the first experiment sodium intake was reduced for 5 weeks in rats aged 3 weeks. Systolic blood pressure, heart rate and plasma renin concentration increased and growth rate was reduced. Sodium intake was then increased for 10 weeks. Blood pressure, heart rate and plasma renin concentration fell and growth rate increased but body weight did not regain control values. As compared with controls, plasma concentrations of aldosterone and corticosterone did not increase after the 10-week period. Thus, sodium depletion did not produce an irreversible change in aldosterone but it did raise arterial pressure. Further experiments confirmed the pressor effect in young and adult rats. Blood pressure was measured in the tail in these experiments but the increase in pressure was not a technical artifact as measurements made in the tail correlated well with measurements made simultaneously by intra-arterial catheter. Catheters were inserted under general anaesthetic for this comparison of pressure and rats previously deprived of sodium showed a significantly higher mortality rate due to the anaesthesia and surgery involved. Thus, a 10-fold reduction of dietary sodium raises blood pressure in young and adult rats and it may increase mortality from a minor surgical procedure. It does not produce irreversible changes in aldosterone.

Aldosterone↗
PubMed1987

Clinical and biochemical effects of the renin inhibitor H142 in humans.

The inhibitor of human renin, H142, was studied in nine male volunteers. On three occasions, in random order, volunteers were infused with 5% dextrose, or with H142 at 1.0 or 2.5 mg/kg/h, for 30 min while supine and thereafter with dextrose for 1.5 h. There was a marked reduction in plasma active renin concentration as assayed by an enzyme-kinetic method, with parallel falls in the circulating concentrations of angiotensins (ANG) I and II, all of which rebounded transiently to values above basal after H142 infusion was stopped. In contrast, total renin concentration as measured by radioimmunoassay rose while ANG I and II fell, subsiding after H142 was discontinued. There was a slight but significant increase in plasma noradrenaline as renin became inhibited: plasma adrenaline was unchanged. H142 produced a slight fall in systolic blood pressure (SBP) and a clearer, highly significant, dose-related fall in diastolic blood pressure (DBP). There was modest but significant increase in the heart rate. These studies confirm H142 as an effective inhibitor of human renin in vivo.

Adult↗
PubMed1987

Hypermineralocorticoidism due to adrenal carcinoma: plasma corticosteroids and their response to ACTH and angiotensin II.

A 47-year-old female presented with hypertension, hypokalaemia, low plasma renin, high plasma aldosterone and was found to have a left adrenal tumour 4 cm in diameter by computerized tomography. Detailed biochemical studies showed high plasma levels of 11-deoxycorticosterone and corticosterone in addition to aldosterone and 18-hydroxycorticosterone. Basal 11-deoxycorticosterone levels were particularly high. Corticosterone, 18-hydroxycorticosterone and aldosterone concentrations were abnormally sensitive to infusions of ACTH and angiotensin II. Plasma cortisol and assays for sex hormones were normal although there was evidence that cortisol derived from the neoplasm. At operation a well-differentiated adrenocortical carcinoma weighing 50 g (56 X 30 X 36 mm) was removed. There was no evidence of metastases following surgery. Adrenal function returned to normal. Review of the literature suggests that adrenocortical carcinoma should be suspected in patients who otherwise have typical features of Conn's syndrome, but whose tumours are more than 3 cm in diameter. Measurement of steroids such as 11-deoxycorticosterone in addition to aldosterone is recommended since abnormally high values may also help to distinguish between hyperaldosteronism due to adenoma and carcinoma. Previously reported cases of isolated aldosterone production by a carcinoma cannot be substantiated.

18-Hydroxycorticosterone↗
PubMed1987

Effects of ACTH and cortisol administration on blood pressure, electrolyte metabolism, atrial natriuretic peptide and renal function in normal man.

Both Adrenocorticotrophin (ACTH) and glucocorticoids raise blood pressure in man and animals, but the relationship of this and altered renal function to other cardiovascular variables, and the differences and similarities of the effects of the two agonists have not been fully explained. The present study compares the effects of ACTH (0.5 mg i.m; every 12 h) and cortisol (50 mg orally, every 6 h) in six normal men over a period of 5 days, preceded and followed by control periods of 3 and 2 days, respectively. Plasma cortisol levels were higher during ACTH treatment than during cortisol treatment. Both treatments raised blood pressure significantly and caused a marked antinatriuresis and expansion of extracellular fluid and plasma volume. ACTH also enhanced potassium excretion but this was less obvious for cortisol. Plasma concentrations of atrial natriuretic peptide rose to more than twice the basal level with both treatments. Both treatments markedly altered renal function. They raised glomerular filtration rate (GFR), i.e. inulin clearance (141% with ACTH; 113% with cortisol) although creatinine clearance was not changed, showing this to be an unreliable index during steroid administration. Filtration fraction (FF) also increased during both treatments, and renal blood flow (RBF) fell, although this achieved statistical significance only during cortisol treatment. Effective renal plasma flow [para-amino hippurate (PAH) clearance] remained unchanged while calculated renal vascular resistance increased. Fractional sodium reabsorption also rose but achieved statistical significance only during ACTH treatment. The similarity of response to treatment suggests that cortisol is largely responsible for the effects of ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1987

Severe hypertension with absent secondary sex characteristics due to partial deficiency of steroid 17 alpha-hydroxylase activity.

A genotypically female patient with 17 alpha-hydroxylase deficiency, and typical symptoms of hypertension, hypokalaemia and lack of secondary sex characteristics, is described. Plasma 17 alpha-hydroxycorticosteroid levels (cortisol, 11-deoxycortisol) and oestradiol were low. Those of 11-deoxycorticosterone, corticosterone, their 18-hydroxy- derivatives, ACTH and gonadotrophins were high and, with the exception of the gonadotrophins, suppressed to normal with dexamethasone which also corrected blood pressure (BP) and electrolyte abnormalities. Plasma aldosterone levels, initially suppressed, increased during treatment but, at 3 months, showed some signs of subnormal responsiveness. Possible reasons for this are discussed. The patient remains well after 9 years on dexamethasone and oestrogen therapy.

Adrenal Cortex Hormones↗
PubMed1987

Angiotensin converting enzyme inhibition in hypertension.

An examination of the principal physiological actions of angiotensin II should make it clear why in vivo attempts to inhibit the rate of angiotensin II generation have been an attractive avenue in pursuing control of high blood pressure. The major physiological effect of angiotensin II relates to its direct pressor effect, but there are supplementary blood pressure regulating actions. Therefore, if we limit the rate of angiotensin II generation by inhibiting the angiotensin converting enzyme (ACE) we should expect to control high blood pressure in a number of clinical syndromes. This paper reviews the future of ACE inhibitors in the treatment of conditions such as hypertension associated with unilateral renal artery stenosis, essential hypertension and severe and previously unresponsive hypertension, with respect not only to efficacy but also to the side-effect profile and ancillary properties. Side effects seen with this class of drug are cough, rashes (both morbilliform and urticarial) and, rarely, angio-oedema. Proteinuria, nephrotic syndrome, leukopenia and taste disturbance were previously reported with captopril but only taste disturbance, and that less frequently, is apparent at the lower doses now employed. Several studies have examined the 'quality-of-life' aspects of ACE therapy and have usually but not always reported favourably. There are features of the ACE inhibitors which make them attractive drugs, and while we should be cautious because of limited experience, we should critically and creatively examine their properties over the next years.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Retinal changes in malignant hypertension.

To assess the diagnostic and prognostic importance of papilloedema in malignant hypertension a two part study was undertaken. Four observers reviewed 56 photographs of fundi from patients with grade 3 or 4 hypertensive retinopathy. Complete agreement on the presence or absence of haemorrhages was recorded in 52 cases and on exudates in 53 cases. Opinion on papilloedema, however, was divided, all four observers agreeing in only 34 cases. In the second part of the study survival in 139 consecutive hypertensive patients with bilateral retinal haemorrhages and exudates was examined by life tables. Ten year survival was 46% in patients with bilateral haemorrhages and exudates alone (n = 43) and 48% when papilloedema was also present (n = 96). Multivariate analysis confirmed that papilloedema was not related to survival. These results suggest that papilloedema is an unreliable physical sign and does not adversely influence prognosis in hypertensive patients who already have bilateral retinal haemorrhages and exudates when effective treatment is available. Papilloedema should no longer be regarded as a necessary feature of malignant hypertension.

Actuarial Analysis↗
PubMed1986

Mortality in patients of the Glasgow Blood Pressure Clinic.

The mortality of 3783 non-malignant hypertensive patients attending the Glasgow Blood Pressure Clinic between 1968 and 1983 and followed for an average of 6.5 years was compared with that in three control groups: the general population of Strathclyde a group of 15 422 subjects aged 45-64 years and screened in Renfrew and Paisley between 1972 and 1976, and a group of hypertensives seen in a blood pressure clinic based on general practice in Renfrew. Average blood pressure for men at entry to the Glasgow Clinic was 181/111 mmHg falling to 158/96 mmHg during treatment. Corresponding values for women were 185/109 mmHg and 161/96 mmHg. Seven hundred and fifty clinic patients (451 males) died during follow-up, the commonest causes of death in both sexes being myocardial infarction and stroke. All-cause age-adjusted mortality (deaths per 1000 patient-years) was 41.4 for men and 22.1 for women. At all ages in both sexes and for all levels of initial blood pressure mortality was less in patients whose blood pressure was reduced most. Without a randomized control group it is not certain that lower mortality in those with well controlled blood pressure was due to treatment, although this is the most likely explanation. Cigarette smoking, a history of myocardial infarction, angina or stroke, retinal arterio-venous nipping, raised blood urea, an abnormal electrocardiogram (ECG) and secondary hypertension were associated with increased risk, but heavy alcohol intake, obesity, haematocrit greater than 45%, hypokalaemia and social class were not. Life table analysis showed that, despite some reduction of mortality by treatment, the relative risk to men and women in the clinic remained two- to five-times that of the general population. The benefits of treatment were not such as to restore normal expectation of life even when blood pressure was well controlled. Excess mortality in the clinic could not be explained by difference of smoking habit or social class. This suggests that there is in the hypertensive patients of the Glasgow Clinic an element of irreducible risk, that treatment may be beneficial in some respects but harmful in others, or that patients at particularly high risk are selectively referred to the clinic.

Actuarial Analysis↗