Professor MacMahonRodgers, Anthony2009-01-282009-01-282001Thesis (PhD--Medicine)--University of Auckland, 2001.http://hdl.handle.net/2292/3361Background Considerable uncertainty exists about the strength and shape of associations of blood pressure and cholesterol with the risks of stroke, coronary heart disease and total cardiovascular death in eastern Asian populations. Therefore, uncertainty also exists about the size of the likely effects on cardiovascular mortality and morbidity of prolonged exposure changes in these populations. The Eastern Stroke and Coronary Heart Disease Collaborative Project was initiated to determine the associations of usual diastolic blood pressure (DBP) and usual cholesterol with the risks of stroke, coronary heart disease (CHD) and total cardiovascular death in cohort studies from eastern Asia. Methods A collaborative overview of cohort studies included data from 13 cohorts from the People’s Republic of China (PRC) and five cohorts from Japan, involving a total of 124,774 participants among whom 837,214 person-years were observed. The overall mean age of participants was 47 years, 43% were current smokers and 39% were female. Both parametric and non-parametric analyses were performed, with adjustments made for several potential confounding factors. Efforts were made to correct for the bias introduced by estimation of "usual" DBP and cholesterol from measurements made at baseline (the "regression dilution" bias). The resulting estimates of associations of blood pressure and cholesterol with cardiovascular diseases were combined with data from surveys of blood pressure and cholesterol levels in Asian and other populations, estimates of the incidence of cardiovascular disease, and results from randomised trials of blood pressure and cholesterol lowering treatments to estimate the possible effects of blood pressure and cholesterol lowering. Findings The overall mean DBP at baseline was 78 mmHg. A total of 1,798 strokes were observed, of which about 45% were confirmed by computed tomography (CT) or autopsy. Each 5 mmHg lower usual DBP was associated with about two-fifths lower non-haemorrhagic stroke risk and about one-half lower haemorrhagic stroke risk(-5 mmHg: odds ratio 0.56, 95% Cl: 0.53-0.59 and 0.69, 0.65-0.73, respectively). The risks were continuous throughout the range of DBP studied (baseline DBP 70-114 mmHg, usual DBP 76-97 mmHg). Each 5 mmHg lower usual DBP was associated with almost a halving of total stroke risk (-5 mmHg: 0.56, 0.53-0.59). The risk of CHD was also strongly and positively related to usual DBP (-5 mmHg: 0.73, 0.66-0.80). Since about half of all cardiovascular deaths were due to stroke, they were strongly related to blood pressure with, on average, each 5 mmHg lower usual DBP associated with about one-third fewer such deaths (-5 mmHg: 0.69, 0.65-0.73). The mean cholesterol at baseline was 4.5 mmol/l (174 mg/dl) and disease risks were assessed across a range of cholesterol levels that correspond approximately to the lower two thirds of the distribution in most Western populations (baseline cholesterol 3.4-6.7mmol/l and estimated usual cholesterol 4.15.8mmol/l). There was a trend toward a negative association of usual cholesterol with strokes classified as haemorrhagic (0.6 mmol/l lower usual cholesterol associated with odds ratio of 1.27, 95% confidence limits 0.84-1.91) and a trend toward a positive association with strokes classified as non-haemorrhagic (-0.6 mmol/l: 0.77, 0.57-1.06). The consequence of these two apparently different (P=0.06) associations, was a weak positive association of usual cholesterol with total stroke (-0.6 mmol/l: O.92, 0.72-1.17). in contrast, there was clear evidence of strong positive associations of usual cholesterol with the risks of CHD (_0.6 mmol/l: 0.47,0.31, 0.71) and of total cardiovascular death (_0.6 mmol/l: 0.58, 0.44-0.76).Overall, there was no clear indication of an interaction between the effects of cholesterol and DBP, when assessed on a multiplicative scale. The estimates of the potential effects of blood pressure lowering indicated that a 3 mmHg lower usual DBP should eventually result in about one-third fewer strokes and one-sixth fewer CHD events. If accompanied by a 0.3 mmol/l lower usual cholesterol, then eventually one-third fewer stroke and CHD events should occur. In the PRC alone, such reductions would be expected to avert over half a million deaths annually. Most events would be prevented in those without hypertension or hypercholesterolaemia. World-wide, a 2% reduction in cholesterol levels would avert about 0'5 million (4%) of CHD deaths in 2020. A 2% reduction in DBP would avert an estimated 1.2 million (16%) stroke deaths and 0.6 million (6%) CHD deaths in 2020. Interpretation Blood pressure is a profoundly important determinant of cardiovascular disease in eastern Asian populations. The relationship observed here between blood pressure and total cardiovascular deaths is steeper than that typically observed in Western populations. This difference appears to be largely due to the different composition of cardiovascular deaths in Eastern populations, with a larger proportion of deaths due to conditions that are strongly related to blood pressure, such as haemorrhagic stroke. In these populations with comparatively low cholesterol from eastern Asia, there was no clear evidence of a cholesterol level below which risks of CHD or total cardiovascular death did not continue to decrease. The strength of the association of cholesterol with CHD was similar to that observed in other populations. The results suggest that modest population-wide reductions in these exposures, particularly blood pressure, could avert a large proportion of the substantial and increasing burden of cardiovascular disease in eastern Asian and other populations.Scanned from print thesisenItems in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htmThesisFields of Research::320000 Medical and Health SciencesCopyright: The authorQ112191398