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Background: The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome. No study, however, has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease (CHD) in hypertensive patients who are not conventionally deemed dyslipidaemic., Methods: Of 19 342 hypertensive patients (aged 40-79 years with at least three other cardiovascular risk factors) randomised to one of two antihypertensive regimens in the Anglo-Scandinavian Cardiac Outcomes Trial, 10,305 with nonfasting total cholesterol concentrations 6.5 mmol/L or less were randomly assigned additional atorvastatin 10 mg or placebo. These patients formed the lipid-lowering arm of the study. We planned follow-up for an average of 5 years, the primary endpoint being non-fatal myocardial infarction and fatal CHD. Data were analysed by intention to treat., Findings: Treatment was stopped after a median follow-up of 3.3 years. By that time, 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group (hazard ratio 0.64 [95% CI 0.50-0.83], p = 0.0005). This benefit emerged in the first year of follow-up. There was no significant heterogeneity among prespecified subgroups. Fatal and non-fatal stroke (89 atorvastatin vs 121 placebo, 0.73 [0.56-0.96], p = 0.024), total cardiovascular events (389 vs 486, 0.79 [0.69-0.90], p = 0.0005), and total coronary events (178 vs 247, 0.71 [0.59-0.86], p = 0.0005) were also significantly lowered. There were 185 deaths in the atorvastatin group and 212 in the placebo group (0.87 [0.71-1.06], p = 0.16). Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months, and by 1.1 mmol/L after 3 years of follow-up., Interpretation: The reductions in major cardiovascular events with atorvastatin are large, given the short follow-up time. These findings may have implications for future lipid-lowering guidelines.

Background: The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome. No study, however, has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease (CHD) in hypertensive patients who are not conventionally deemed dyslipidaemic., Methods: Of 19342 hypertensive patients (aged 40-79 years with at least three other cardiovascular risk factors) randomised to one of two antihypertensive regimens in the Anglo-Scandinavian Cardiac Outcomes Trial, 10305 with non-fasting total cholesterol concentrations 6.5 mmol/L or less were randomly assigned additional atorvastatin 10 mg or placebo. These patients formed the lipid-lowering arm of the study. We planned follow-up for an average of 5 years, the primary endpoint being non-fatal myocardial infarction and fatal CHD. Data were analysed by intention to treat., Findings: Treatment was stopped after a median follow-up of 3.3 years. By that time, 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group (hazard ratio 0.64 [95% CI 0.50-0.83], p=0.0005). This benefit emerged in the first year of follow-up. There was no significant heterogeneity among prespecified subgroups. Fatal and non-fatal stroke (89 atorvastatin vs 121 placebo, 0.73 [0.56-0.96], p=0.024), total cardiovascular events (389 vs 486, 0.79 [0.69-0.90], p=0.0005), and total coronary events (178 vs 247, 0.71 [0.59-0.86], p=0.0005) were also significantly lowered. There were 185 deaths in the atorvastatin group and 212 in the placebo group (0.87 [0.71-1.06], p=0.16). Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months, and by 1.1 mmol/L after 3 years of follow-up., Interpretation: The reductions in major cardiovascular events with atorvastatin are large, given the short follow-up time. These findings may have implications for future lipid-lowering guidelines.

Objective: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l., Design: Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component., Setting: Patients were recruited mainly from general practices., Patients: Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization., Interventions: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily., Main Outcome Measure: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD)., Results: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors., Conclusions: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.

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.

NATURE OF RELATIONSHIP BETWEEN HYPERTENSION AND CORONARY ARTERY DISEASE: Epidemiological data indicate a strong and consistent link between hypertension and coronary artery disease. This does not mean that hypertension is the cause of coronary artery disease. Less than a quarter of the risk of developing coronary artery disease can be attributed to raised blood pressure. Furthermore, in individuals, hypertension is only weakly predictive and hence blood pressure cannot be relied upon to identify those with a particularly high risk. EFFECT OF A REDUCTION IN BLOOD PRESSURE ON CORONARY ARTERY DISEASE: The results of outcome trials, largely in men with mild to moderate uncomplicated hypertension, demonstrate that a modest short-term reduction in blood pressure confers a reduction in coronary artery disease events of about 16%, against the expectation from observational studies of about 22.5%. Explanations for the apparent shortfall include the putative theory that metabolic effects of the drugs used in the trials (mainly thiazides and beta-blockers) offset the beneficial effect of the blood pressure reduction. However, from consideration of epidemiological findings, it is clear that a large proportion (over 75%) of events in hypertensive patients is unlikely to be preventable by managing the elevated blood pressure alone. TREATMENT CONSIDERATIONS: Since arterial pressure interacts in a more than additive manner with coincident coronary risk factors, treatment should be initiated on the basis of overall risk and directed by predictors of myocardial infarction. In addition to a sustained level of blood pressure, these predictors include established coronary artery disease, older age and cigarette smoking. BEYOND BLOOD PRESSURE REDUCTION: Whether metabolically neutral antihypertensive drugs can reduce the shortfall between expected and observed benefit remains uncertain. However, some newer agents (angiotensin converting enzyme inhibitors and calcium antagonists) appear to have an effect on vascular structure and function that is independent of blood pressure reduction. If these advantages are confirmed in clinical trials, these drugs offer the prospect of a much greater impact on coronary artery disease than currently obtained.

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.