Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people

Abstract

Background: The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease.

Methods: We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371.

Findings: During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years.

Interpretation: The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them.

Funding: Medical Research Council, National Institute for Health Research, and Wellcome Trust.

Figure 1

Forest plot of HRs (95% CIs) per 20/10 mm Hg increase in systolic (black) or diastolic (grey) blood pressure, adjusted for age and sex The vertical dashed lines correspond to the associations of SBP (black) or DBP (grey) with total cardiovascular disease. Adjustments include age, quadratic age, and stratification by sex and primary care practice. CIs are Bonferroni corrected (13 endpoints × 2 variables=26 tests). HR=hazard ratio. SBP=systolic blood pressure. DBP=diastolic blood pressure.

Figure 2

Forest plots of HRs (95% CIs) for 20/10 mm Hg changes in blood pressure in different age groups, adjusted for age and sex Models included continuous age, age group, interaction between blood pressure and age group (which is the association reported in the forest plot), and stratification by sex and primary care practice. CIs are Bonferroni corrected (3 age groups × 12 endpoints=36 tests). HR=hazard ratio.

Figure 3

Forest plots of HRs (95% CIs) for different cutoffs of systolic blood pressure (vs reference 115 mm Hg) adjusted for age and sex Blood pressure was modelled as a continuous variable with splines with three knots. Adjustments include age, quadratic age, and stratification by sex and primary care practice. CIs are Bonferroni corrected (3 age groups × 6 categories × 12 endpoints=216 tests). HR=hazard ratio.

Figure 4

Forest plot of HRs (95% CIs) for different cutoffs of diastolic blood pressure (vs reference 75 mm Hg) adjusted for age and sex Blood pressure was modelled as a continuous variable with splines with three knots. Adjustments include age, quadratic age, and stratification by sex and primary care practice. CIs are Bonferroni corrected (3 age groups × 6 categories × 12 endpoints=216 tests). HR=hazard ratio.

Figure 5

Lifetime risk (95% CI) of 12 different cardiovascular diseases in people with hypertension or normal BP from index age 30 years Hypertension was defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg or use of BP-lowering treatments or physician-recorded diagnosis at baseline. BP=blood pressure.

Figure 6

Years of life lost to cardiovascular disease up to 95 years of age associated with hypertension at index ages 30, 60, and 80 years, adjusted for sex, smoking, diabetes, and total and high-density lipoprotein cholesterol 83 098 total cardiovascular disease events occurred.