Independent effects of smoking on risk of hypertension: small, if present.
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Age Factors↗
Biomedical subjects
Neil R Poulter
Publications and source records attributed to Neil R Poulter.
Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial.
BACKGROUND: The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics and beta blockers. Our aim, therefore, was to compare the effect on non-fatal myocardial infarction and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril. METHODS: We did a multicentre, prospective, randomised controlled trial in 19 257 patients with hypertension who were aged 40-79 years and had at least three other cardiovascular risk factors. Patients were assigned either amlodipine 5-10 mg adding perindopril 4-8 mg as required (amlodipine-based regimen; n=9639) or atenolol 50-100 mg adding bendroflumethiazide 1.25-2.5 mg and potassium as required (atenolol-based regimen; n=9618). Our primary endpoint was non-fatal myocardial infarction (including silent myocardial infarction) and fatal CHD. Analysis was by intention to treat. FINDINGS: The study was stopped prematurely after 5.5 years' median follow-up and accumulated in total 106 153 patient-years of observation. Though not significant, compared with the atenolol-based regimen, fewer individuals on the amlodipine-based regimen had a primary endpoint (429 vs 474; unadjusted HR 0.90, 95% CI 0.79-1.02, p=0.1052), fatal and non-fatal stroke (327 vs 422; 0.77, 0.66-0.89, p=0.0003), total cardiovascular events and procedures (1362 vs 1602; 0.84, 0.78-0.90, p<0.0001), and all-cause mortality (738 vs 820; 0.89, 0.81-0.99, p=0.025). The incidence of developing diabetes was less on the amlodipine-based regimen (567 vs 799; 0.70, 0.63-0.78, p<0.0001). INTERPRETATION: The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen. On the basis of previous trial evidence, these effects might not be entirely explained by better control of blood pressure, and this issue is addressed in the accompanying article. Nevertheless, the results have implications with respect to optimum combinations of antihypertensive agents.
Adrenergic beta-Antagonists↗
Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA).
BACKGROUND: Results of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) show significantly lower rates of coronary and stroke events in individuals allocated an amlodipine-based combination drug regimen than in those allocated an atenolol-based combination drug regimen (HR 0.86 and 0.77, respectively). Our aim was to assess to what extent these differences were due to significant differences in blood pressures and in other variables noted after randomisation. METHODS: We used data from ASCOT-BPLA (n=19 257) and compared differences in accumulated mean blood pressure levels at sequential times in the trial with sequential differences in coronary and stroke events. Serial mean matching for differences in systolic blood pressure was used to adjust HRs for differences in these events. We used an updated Cox-regression model to assess the effects of differences in accumulated mean levels of various measures of blood pressure, serum HDL-cholesterol, triglycerides and potassium, fasting blood glucose, heart rate, and bodyweight on differences in event rates. FINDINGS: We noted no temporal link between size of differences in blood pressure and different event rates. Serial mean matching for differences in systolic blood-pressure attenuated HRs for coronary and stroke events to a similar extent as did adjustments for systolic blood-pressure differences in Cox-regression analyses. HRs for coronary events and stroke adjusted for blood pressure rose from 0.86 (0.77-0.96) to 0.88 (0.79-0.98) and from 0.77 (0.66-0.89) to 0.83 (0.72-0.96), respectively. Multivariate adjustment gave HRs of 0.94 (0.81-1.08) for coronary events (HDL cholesterol being the largest contributor) and 0.87 (0.73-1.05) for stroke events. INTERPRETATION: Multivariate adjustment accounted for about half of the differences in coronary events and for about 40% of the differences in stroke events between the treatment regimens tested in ASCOT-BPLA, but residual differences were no longer significant. These residual differences could indicate inadequate statistical adjustment, but it remains possible that differential effects of the two treatment regimens on other variables also contributed to the different rates noted, particularly for stroke.
Adult↗
Measures of global risk: old versus new methods.
It is clear that atherosclerotic arterial disease has a multifactorial aetiology. Furthermore relatively modest elevations of two or more risk factors frequently coexist in individuals to produce a significant impact on the likelihood of a cardiovascular event. Nevertheless clinical practice has tended to be unifactorial, with physicians concentrating on single risk factors in isolation. Various scores using data on several risk factors have therefore been developed to help physicians assess which of their patients are most at risk and therefore most merit intervention. This global risk assessment is increasingly recognised in management guidelines as a reasonable way of guiding treatment. Indeed intervention strategies that do not target those at highest cardiovascular risk--(and currently available risk scores do this more efficiently than physicians' judgement)--are less likely to be cost effective. It must be acknowledged however that all risk scores have limitations and hence whichever method is used should be used to guide rather than rule practice.
Arteriosclerosis↗
Modulating the design of clinical trials to address the question of mechanisms of disease.
The evaluation of causation of a disease is judgemental. It should be based on an overview of how far the observed association satisfies several criteria, including its strength, dose response, temporal sequence, independence, consistency, presence of a plausible mechanism, predictive power, and reversibility. Whilst the results of randomised controlled trials are frequently incorrectly considered as proof (or otherwise) of causation, what they do allow is an evaluation of the reversibility of disease. Whilst reversibility is one of the criteria which allows causation to be judged and randomised trials are reasonably considered as the 'gold standard' study design, they do not necessarily shed light on mechanisms of disease, particularly in the context of chronic degenerative disorders such as those underpinned by the atherosclerotic process.
Humans↗