Pulse pressure (PP) has been claimed to be superior to systolic blood pressure (SBP) and diastolic blood pressure (DBP) as a predictor of cardiovascular (CV) risk. In this study we assessed the hypothesis that high PP would predict CV mortality in a general population, and tested the predictive value of a novel expression of PP designed to overcome the confounding influence of the strong co-linearity between PP and SBP. A cohort of 15,406 men and women aged 45 – 64 years from a general population were screened for BP and other cardiovascular risk factors in the 1970s and followed-up for dates and causes of death by linkage with the Registrar General (Scotland). A measure of PP not confounded by the strong relationship with SBP (r2 = 0.84) was derived for each individual (conditional PP). Conditional PP = actual PP - expected PP (average PP in population with the same DBP, adjusted for age and gender). Conditional PP was tested for statistical independence from SBP and then included in a Cox proportional hazard model along with other BP measures and risk factors as a predictor of CV risk. By 2001, 8,192 (53%) individuals were dead, 51% from CV causes: 32% coronary artery disease (CAD), 12% stroke. After adjustment for age, smoking and serum cholesterol, SBP, DBP and PP were each significant (p < 0.001) single predictors for CAD, stroke and all cause mortality, in males and in females. Except for stroke mortality in females where DBP was the best predictor, SBP was most strongly correlated with risk. In all cases, PP was by far the least informative variable. For CAD mortality, this rank order of risk prediction was consistent across the age range. After adjustment for confounding factors including SBP, conditional PP was inversely associated with risk; low conditional PP was associated with highest risk, while high conditional PP at entry predicted the lowest risk. The effect of the low conditional PP as a risk factor appeared to be consistent for different cause specific-outcomes and across the range of SBP, and to be independent of age. In conclusion, a high PP in middle-aged individuals does not predict cardiovascular mortality and SBP is the most consistent and reliable predictor.

Three questions related to cancer and blood pressure are discussed. (i) Is cancer related in some way to hypertension, or to blood pressure? Several studies show a relation of blood pressure and cancer in populations. However, our own experience, based on a cohort of 15,411 subjects with BP measured in the 1970s and with 1,392 fatal cancers since, shows no relation of cancer risk and diastolic pressure. Nor were cancer numbers (n=72) observed in the 1,078 untreated hypertensives of the Glasgow Blood Pressure Clinic different from those expected (n=71.2) in a control population matched for age, sex and smoking habit. (ii) Do antihypertensive drugs promote cancer? Atenolol and calcium channel blockers have been suspected of this, but evidence of larger studies, including two of our own, is negative: relative risk for cancer in our patients taking CCB was 1.02 (CI 0.82-1.27). (iii) Do antihypertensive drugs protect against cancer? A study of ours based on the Glasgow Clinic raises this possibility: relative risk for incident cancer amongst 1,559 patients taking ACE inhibitor was 0.72 (CI 0.55-0.92).

OBJECTIVES The purpose of the study was to assess the effect of lipid reduction with pravastatin on hospital admissions in middle-aged men with hypercholesterolemia in the West of Scotland Coronary Prevention Study.BACKGROUND A prospective, randomized controlled trial was undertaken in primary care centers in the West of Scotland.METHODS A total of 6,595 participants randomized to receive pravastatin 40 mg or placebo daily were followed up for a mean of 4.9 years (range 3.5 to 6.1 years). Analysis of hospital admissions was undertaken according to the "intention to treat" principle both for cardiovascular diseases and noncardiovascular diseases (including malignant neoplasms, psychiatric diagnoses, trauma and other causes). A secondary analysis of hospitalization in patients who were greater than or equal to 75% compliant was performed.RESULTS During the trial, 2,198 (33%) of the 6,595 men were admitted to hospital on 4,333 occasions, of which 1,234 (28%) were for cardiovascular causes. Pravastatin reduced the number of subjects requiring hospital admission for cardiovascular causes by 21% (95% CI [confidence interval] 9 to 31, p = 0.0008) overall, and by 27% (95% CI 15 to 38) in compliant participants. The number of admissions per 1,000 subject-years for cardiovascular disease was reduced by 10.8 (95% CI 4 to 17.4, p = 0.0013) in all subjects, and by 15.6 (95% CI 8.3 to 23, p < 0.0001) in compliant participants. Pravastatin had no significant influence on hospital admission for any noncardiovascular diagnostic category. There were 13.4 fewer admissions per 1,000 subject years for all causes in the pravastatin-treated group (95% CI -0.4 to 27.3, p = 0.076). No significant difference in duration of hospital stay was found between the pravastatin and placebo patients in any diagnostic group.CONCLUSIONS Pravastatin therapy reduced the burden of hospital admissions for cardiovascular disease, without any adverse effect on noncardiovascular hospitalization. (J Am Coll Cardiol 1999;33:909-15) (C) 1999 by the American College of Cardiology.

Established in 1968 the Glasgow Blood Pressure Clinic has over 11,000 patients on its computer record. Up to 1980, mortality from all-causes and from cardiovascular causes was high: relative risks compared with two local control populations were greater than 2.0. Since 1980, all-cause mortality has decreased to 1.31 (859 deaths, CI 1.23-1.39). Lower mortality from cardiovascular causes, particularly coronary heart disease, contributes to the decrease. Reasons for the decrease are under investigation currently. Referral of patients with slightly lower blood pressure contributes, as may better blood pressure control with newer antihypertensive drugs. ACE inhibitors and calcium channel blockers were introduced in 1980 and during the 16-year period to 1995, all-cause mortality has decreased most in patients taking ACE inhibitor. A decrease also occurred in patients taking antihypertensive drugs other than ACE inhibitor.

OBJECTIVE:To measure rates of incident and fatal cancer in hypertensive patients taking calcium antagonists and to compare these with rates in three control groups. DESIGN:A retrospective analysis of cancer in patients of the Glasgow Blood Pressure Clinic prescribed either a calcium antagonist or other antihypertensive drugs (non-calcium antagonist group). Record linkage of the clinic with the West of Scotland Cancer Registry and with the Registrar General, Scotland provided information on incidence of cancer and on deaths and their causes. PATIENTS:2297 patients were prescribed calcium antagonist and 2910 were prescribed antihypertensive drugs other than calcium antagonist. MAIN OUTCOME MEASURES:Relative risk of cancer, the ratio of observed to expected cancers in the calcium antagonist group, was estimated using expected values based on three control groups; namely the non-calcium antagonist group, a middle-aged population of Renfrew and Paisley and the West of Scotland population. RESULTS:There were 134 incident cancers in the calcium antagonist group, representing relative risks of 1.02 [95% confidence interval (CI) 0.82-1.271 compared with the non-calcium antagonist group, 1.01 (95% CI 0.84-1.18) compared with Renfrew-Paisley controls and 1.02 (95% CI 0.85-1.19) compared with West of Scotland controls. Findings for cancer mortality were similarly negative. Risks were no higher for older patients. CONCLUSIONS:Our study lends no support to the suggestion that calcium antagonists cause cancer.

Background Previous studies have reported an increased risk of cancer with calcium-channel blockers in man. Other work in animals suggests that inhibitors of angiotensin-1-converting enzyme (ACE) protect against cancer. We aimed to assess the risk of cancer in hypertensive patients receiving ACE inhibitors or other antihypertensive drugs.Methods Our retrospective cohort study was based on the records of 5207 patients who attended the Glasgow Blood Pressure Clinic between Jan 1, 1980, and Dec 31, 1995. The patients' records are linked with the Registrar General Scotland and the West of Scotland Cancer Registry.Findings Compared with the West of Scotland controls, the relative risks of incident and fatal cancer among the 1559 patients receiving ACE inhibitors were 0.72 (95% CI 0.55-0.92) and 0.65 (0.44-0.93). Among the 3648 patients receiving antihypertensive drugs other than ACE inhibitors (calcium-channel blockers 1416, diuretics 2099, beta-blockers 2681), the corresponding relative risks were 1.10 (0.97-1.22) and 1.03 (0.87-1.20). The relative risk of cancer was lowest in women on ACE inhibitors: 0.63 (0.41-0.93) for incident cancer; 0.48 (0.23-0.88) for fatal cancer; and 0.37 (0.12-0.87) for female-specific cancers. The reduced relative risk of cancer in patients on ACE inhibitors was greatest with follow-up of longer than 3 years. Calcium-channel blockers, diuretics, and beta-blockers had no apparent effect on risk of cancer.Interpretation Long-term use of ACE inhibitors may protect against cancer. The status of this finding is more that of hypothesis generation than of hypothesis testing; randomised controlled trials are needed.

The West of Scotland Coronary Prevention Study recently demonstrated the benefits of pravastatin therapy in the prevention of coronary heart disease events in middle-aged hypercholesterolemic men without prior myocardial infarction. We present an analysis of the influence of baseline risk factors on coronary events and total mortality in the trial, and their interaction with therapy, using the Cox proportional hazards model. The multivariate predictors of fatal or nonfatal coronary events were treatment allocation (pravastatin or placebo), current smoking, diabetes mellitus, nitrate consumption, minor electrocardiographic abnormalities, angina pectoris, family history of premature coronary death, widowhood, blood pressure, and total cholesterol/high density lipoprotein cholesterol ratio. Independent of other risk factors, pravastatin reduced the risk of definite coronary heart disease death or nonfatal myocardial infarction by 32% (95% confidence interval 17 to 44, p = 0.0001), definite or suspected coronary heart disease death by 35% (3 to 56, p = 0.035), cardiovascular death by 33% (4 to 53, p = 0.027), coronary revascularization procedures by 38% (11 to 56, p = 0.009), and all-cause mortality by 24% (2 to 41, p = 0.037). The 5-year risk of fatal or nonfatal myocardial infarction, calculated using the predictors identified in the Cox analysis, ranged from <4.4% in the lowest quartile of risk to >9.6% in the highest quartile. The proportional benefit achieved by pravastatin was independent of other risk factors; hence, the absolute benefit of therapy was greatest in subjects with the highest baseline risk. Such subjects can be identified easily in the population and deserve high priority for treatment. (C) 1997 by Excerpta Medica, Inc.

Four faults are reported in the Hawksley Random Zero Sphygmomanometer (RZS). Our study is of their mechanism. (i) Compared with a mercury sphygmomanometer the RZS underestimates blood pressure (BP). We confirm this: for 240 measurements by three experienced operators in 12 patients, systolic BP was 3.4 mm Hg lower in the RZS; diastolic pressure was not underestimated. A cause of under-estimation in 89% of measurements was that mercury stuck in the manometer giving a false high reading of random zero (RZ). Tilting the RZS before reading RZ reduced under-reading by 1.6 mm Hg. A rare cause is failure of the operator to completely close the reservoir tap. (ii) Values of RZ are not randomly distributed; non-randomness is most marked in measurements made by experienced operators whose speed of measurement provides insufficient time during cuff inflation for filling of the diaphragm chamber. Smaller contributions are made by the sticking of mercury in the manometer and by a leak of air through the air bleed screw. (iii) Consecutive RZ estimates often have similar value. This has two causes: short cuff inflation time and short interval between opening the reservoir tap and spinning the thumb-wheel. (iv) An inverse relation of RZ and BP suggested by earlier work and by our own data is probably an artifact: when BP is low, measurement is quick and RZ is falsely high; when BP is high, measurement takes longer and RZ is lower. These four faults could be partly or wholly avoided by a change in the operators' technique.

Annual Scientific Meeting of the British Hypertension Society: Wills Hall, University of Bristol, 15–17 September 1997

Aims To assess the additional benefit gained from high compliance in the West of Scotland Coronary Prevention Study and to examine cases where withdrawal from trial medication was due to an adverse event.Methods The incidence of definite coronary heart disease or non-fatal myocardial infarction, cardiovascular mortality, definite or suspect coronary heart disease death or non-fatal myocardial infarction, the need for coronary revascularization procedures, all-cause mortality and incident cancers were measured in the entire cohort and compared with the high compliance group. The adverse events associated with withdrawal were coded by body system.Results In subjects with compliance greater than or equal to 75%, treatment with pravastatin resulted in a 38% risk reduction for definite coronary heart disease death or non-fatal myocardial infarction and for cardiovascular mortality, a 46% reduction in risk or coronary revascularization and a 32% risk reduction (P = 0.015) for all-cause mortality.Conclusions The analysis of the effect of pravastatin in the subgroup of high compliers to randomized medication demonstrated a substantial increase in the estimated risk reductions in comparison with that achieved in the intention-to-treat analysis. This result has significant implications for the motivation of high compliance among patients and for the assessment of the cost-effectiveness of treatment.

Background Increased activity of the sympathetic nervous system has been proposed as a cause of high blood pressure (BP) and may be related to diet and body weight. To determine the role of these factors in predisposition to high BP, we studied 100 young adults with high or low BP from families in which both parents had either high or low BP. Methods and Results Plasma catecholamine, glucose, and insulin levels were measured before and after an oral glucose load. There was a significant correlation between fasting plasma norepinephrine and mean arterial pressure ( P =.001). Subjects with high BP, irrespective of parental BP, were heavier ( P =.003) and fatter ( P =.002) and had a greater rise in plasma insulin ( P =.003) following glucose than those with low BP. Offspring with high BP whose parents also had high BP showed an unexpected rise in plasma epinephrine ( P =.004) following glucose. This adrenal medullary response was not the result of high parental or high personal BP alone as it was not seen in offspring with low BP whose parents had high BP or in offspring with high BP whose parents had low BP. Conclusions Irrespective of family history, high BP is associated with increased body weight and hyperinsulinemia and reflects personal environment and behavior. However, abnormal epinephrine release is characteristic of the combination of genetic, environmental, and behavioral factors that is associated with high personal BP and a familial predisposition to high BP.

We studied the influence of gender on the relations between cholesterol and coronary mortality, and between diastolic blood pressure and stroke mortality, Men (n=7137) and women (n=8262) aged 45-64 years from Renfrew and Paisley in the west of Scotland were first examined in 1972-76, and then followed for 17 years. Coronary and stroke mortality were calculated as deaths per thousand patient-years, and adjusted for the effects of competing risk factors. Plasma cholesterol was positively related to coronary mortality in both sexes. Absolute risk of coronary death was however, so much less in women that a woman with high cholesterol (> 7.2 mmol/l) was at lower risk than a man with low cholesterol (<5.0 mmol/l). Diastolic blood pressure was positively related to stroke mortality in both sexes, but here the absolute risks were similar in each Sex. Stroke mortality was highest in hypertensive men and women who smoked and had hyperlipidaemia. Although for primary prevention of stroke by treatment of hypertension, similar management could be used in men and women, primary prevention of coronary disease by lipid-lowering may well require different policies for the two sexes, corresponding to their different absolute risk and potential for benefit.

BACKGROUND:We studied the correlates of left ventricular mass (LVM) in 84 healthy young adults aged 16 to 24 years from the general population. Subjects were selected according to predisposition to hypertension into four groups with either high or low personal blood pressures and either high or low parental blood pressures.METHODS AND RESULTS:LVM was measured by echocardiography, and measurements of blood pressure, heart rate, body dimensions, and plasma concentrations of components of the renin-angiotensin system were made under resting conditions. LVM was similar in individuals predisposed to hypertension (high personal and parental blood pressures) and those with contrasting predisposition (low personal and parental pressures). Regression analysis of the combined groups showed that LVM correlated closely with body size, particularly lean body mass (r=.69, P<.0001) and systolic (r=.35, P<.0001) but not diastolic blood pressure. Plasma angiotensin II (r=.39, P<.0001), renin (r=.302, P<.01), and angiotensin-converting enzyme (r=.22, P<.05) showed significant correlation with LVM. Multiple regression analysis revealed that plasma angiotensin II was the most important component of the renin-angiotensin system and that its effect was independent of systolic blood pressure and body size.CONCLUSIONS:These findings provide evidence in humans that angiotensin II exerts a direct on myocardial size. This association may have important implications for the complications and treatment of left ventricular hypertrophy.

Background We assessed the potential benefit of treatment for low-risk and high-risk groups in the West of Scotland Coronary Prevention Study (WOSCOPS) population, and compared the benefits of primary and secondary prevention of coronary heart disease (CHD) by lipid lowering with the benefits of blood pressure reduction in the primary prevention of stroke.Methods We did a subgroup analysis of placebo-treated men in the WOSCOPS population by age, vascular disease at trial entry, and other established risk factors. We also compared WOSCOPS findings with those of the Scandinavian Simvastatin Survival Study (4S) and the Medical Research Council (MRC) trial of treatment for mild to moderate hypertension in middle-aged men. The WOSCOPS population comprised 6595 men aged 45-64 years with no history of myocardial infarction (MI) and plasma total cholesterol concentrations of 6 . 5-8 . 0 mmol/L at initial screening. Participants were randomly allocated pravastatin (40 mg daily) or placebo, and followed up for an average of 4 . 9 years.Findings Coronary event rates at 5 years in the WOSCOPS placebo group were higher than 10% (the recommended treatment threshold) in men with pre-existing vascular disease and in those 55 years or older without symptoms least one other low in men with hypercholesterolaemia but no other risk factor: 3 . 5% (95% CI 1 . 3-5 . 7) for men aged 45-54 years and 5 . 3% (2 . 7-8 . 0) for men aged 55-64 years. Three times more men had to be treated for 5 years to prevent one endpoint in WOSCOPS than in 4S, By contrast, two to four times fewer men with hyperlipidaemia were treated to save one coronary event in WOSCOPS than hypertensives to save one stroke in the MRC trial. These differences persisted after adjustment for the low-risk status of many of the patients with hypertension who took part in the MRC trial.Interpretation There were a substantial number of men whose risk of a coronary event was more than 10% at 5 years in the WOSCOPS cohort, The absolute benefit of pravastatin treatment of hyperlipidaemia is less in the primary prevention of CHD than in secondary prevention, but is similar to that for primary prevention of stroke by treatment of mild to moderate hypertension in middle-aged men.