Abstract
Background: The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China. Methods: 512 891 adults (59% women) aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure. Findings: During a median follow-up of 9 years (IQR 8–10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40–79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28–1·34]) and ischaemic stroke (1·30 [1·29–1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65–1·71]). HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35–1·44]) and diabetes (1·14 [1·12–1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (<80 years of age) annually. Interpretation: Among adults in China, systolic blood pressure was continuously related to major vascular disease with no evidence of a threshold down to 120 mm Hg. Unlike previous studies in high-income countries, blood pressure was more strongly associated with intracerebral haemorrhage than with ischaemic stroke. Even small reductions in mean blood pressure at a population level could be expected to have a major impact on vascular morbidity and mortality. Funding: UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, and the National Science Foundation of China.
| Original language | English |
|---|---|
| Pages (from-to) | e641-e649 |
| Journal | The Lancet Global Health |
| Volume | 6 |
| Issue number | 6 |
| Early online date | 14 May 2018 |
| DOIs | |
| Publication status | Published - 1 Jun 2018 |
Bibliographical note
Publisher Copyright:© 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Funder
In this Chinese population, usual blood pressure was positively and log-linearly associated with risk of ischaemic heart disease, ischaemic stroke, intracerebral haemorrhage, and the aggregate of all major vascular diseases. These relationships continued down to at least 120 mm Hg systolic blood pressure and 75 mm Hg diastolic blood pressure, below which the evidence was scarce. The associations attenuated with increasing age, but even at ages 70–79 years there were strong associations with each of the main types of vascular disease. At all ages, there were steeper associations between blood pressure and intracerebral haemorrhage than ischaemic stroke. We estimated that about half of all premature vascular deaths were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg). Our study showed stronger associations between blood pressure and vascular disease than have previous prospective studies in China, largely because those studies did not correct for within-person variability in blood pressure (regression dilution bias). 21–23 Compared with previous large meta-analyses of prospective studies that corrected for regression dilution (the Prospective Studies Collaboration 4 and the Asia Pacific Cohort Studies Collaboration 5 ), the findings are consistent for ischaemic heart disease but differ somewhat for stroke types. By contrast with these meta-analyses, our study found strong evidence that, throughout middle age and into old age, there were steeper associations for intracerebral haemorrhage than ischaemic stroke. These differences might, in part, reflect the high rate of brain imaging in this study. The use of brain imaging for diagnosis of stroke types was less common before the mid-1990s and, hence, it is possible that there was substantial misclassification of stroke types in some of the older studies included in these meta-analyses. By contrast, brain imaging was used to diagnose stroke types in about 90% of stroke cases in the CKB study. The greater use of brain imaging might also have allowed more non-fatal strokes to be identified than previously. There were shallower associations for non-fatal than fatal ischaemic stroke (unlike for intracerebral haemorrhage), and there is some evidence that both case fatality and the strength of associations with blood pressure might differ between the different aetiological subtypes of ischaemic stroke (large-artery atherosclerosis, small-vessel disease, cardioembolism, or other pathology). 8,24 Information on subtypes of ischaemic stroke is not yet available in the present study, but small-vessel (lacunar) infarcts, with low case fatality, might well be more common in Chinese than white populations. 25 Randomised controlled trials 6,26 of blood-pressure-lowering medication have shown the reversibility of some of the excess vascular risks associated with elevated blood pressure. A comparison of the findings from blood-pressure-lowering trials with the predicted effects of blood pressure from prospective cohort studies suggests that about 60% of the predicted risks of ischaemic heart disease and 80% of the predicted risks of stroke were reversed within 4–5 years of initiating treatment. 26 Furthermore, the trial results indicate that the proportional effects of blood pressure on vascular risk were similar among people with and without cardiovascular disease, so the absolute benefits are very much greater among those with existing disease. 6 Similarly, the absolute benefits of blood pressure lowering are likely to be greater in older than younger adults, given the greater absolute risk of vascular disease at older age. Guidelines on the management of hypertension generally recommend initiating treatment in adults with an average systolic blood pressure of 140 mm Hg or more, or diastolic blood pressure of 90 mm Hg or more, and some recent randomised trials, in selected populations, have found benefit in initiating treatment at lower levels. 27,28 However, the use of blood-pressure-lowering treatment in China is much lower than in western populations. 29 Our previous analyses of the CKB study indicate that, consistent with nationally representative surveys in China, 30,31 about a third of adults had hypertension at baseline (defined as systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mm Hg, or receiving treatment for hypertension). 32 Of those with hypertension, about a third were diagnosed; of those diagnosed, about half were treated; and, of those treated, about a third had their hypertension controlled. The result was that less than 5% of participants with hypertension achieved properly controlled blood pressure. Previous studies reported associations between blood pressure variability and risk of vascular disease independently of baseline systolic blood pressure, 33,34 but there were an insufficient number of repeat blood pressure measures to assess any such effects in this study. However, other studies have suggested that, after correction for regression dilution bias in blood pressure variability, the effects of any such variability in systolic blood pressure on risk of vascular diseases, independent of usual levels of systolic blood pressure, are likely to be modest. 35 We observed significant positive associations between systolic blood pressure and chronic kidney disease and diabetes, but the causal relevance of these associations remains uncertain. Neither association is strongly supported by evidence from trials, and might well be accounted for by reverse causality or residual confounding. A large meta-analysis 6 of randomised controlled trials of blood-pressure-lowering medications reported that lowering blood pressure had no significant effect on the incidence of renal failure (10 mm Hg lower systolic blood pressure was associated with RR 0·95 [95% CI 0·84–1·07]). However, renal failure might not be entirely consistent with chronic kidney disease as defined in this study (the level of renal impairment among incident chronic kidney disease cases was not available). For diabetes, there is some evidence from randomised trials that lower blood pressure is associated with a reduced incidence of diabetes, but the effects are limited to certain medications only (angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers), indicating that the renin–angiotensin system might be causally related to diabetes rather than actual levels of blood pressure. 36 The chief strengths of this study include the large number of disease events, high-quality measurements of blood pressure (including the training of technicians), and long-term follow-up of a wide range of clinically validated disease outcomes. The main findings support efforts to address the substantial burden of blood pressure on vascular disease in China, and indicate that even small reductions in mean blood pressure at a population level can have a substantial effect on disease risk: for example, 5 mm Hg lower usual blood pressure would prevent around 350 000 deaths per year among individuals younger than 80 years of age (and around 200 000 deaths at <70 years). The use of blood-pressure-lowering medication is low in China, and strategies to improve rates of awareness, detection, and treatment of individuals with hypertension are likely to be highly cost-effective, especially among those with existing vascular disease. 37 In the absence of well developed primary care systems, population-based approaches are also required to address the major determinants of elevated blood pressure in China, including high sodium intake (eg, through salt reduction), high alcohol consumption, excess adiposity, lack of regular physical activity, and poor home heating in winter. 38–40 In conclusion, among men and women in China, higher levels of blood pressure were continuously and positively associated with higher risks of major vascular disease, with no evidence of a threshold down to at least 120 mm Hg systolic blood pressure and 75 mm Hg diastolic blood pressure. Unlike studies in western populations, blood pressure was more strongly associated with intracerebral haemorrhage than ischaemic stroke. There was also evidence of positive associations with some non-vascular chronic diseases, but the causality of these associations remains unclear. It was estimated that about half of all vascular deaths in China were attributable to elevated blood pressure, accounting for roughly 1 million deaths (age <80 years) annually; given the strength of the associations between blood pressure and vascular disease, even small reductions in mean blood pressure at a population level would be expected to have a major impact on vascular morbidity and mortality. Contributors BL, SL, RCl, ZC, and LL designed and planned the paper; BL, XLK, SL, RCl, ZC, and LL were involved in data analysis, interpretation, and reporting; BL, SL, RCl, ZC, and LL were involved in manuscript drafting; RCl, ZC, LL, RP, RCo, RGW, YG, and JC, as members of China Kadoorie Biobank steering committee, designed and supervised the overall conduct of the study and obtained funding. YG, YC, ZB, and ZC coordinated the data acquisition (for baseline surveys, resurveys, and long-term follow-up). All authors provided critical comments on the manuscript. Declaration of interests We declare no competing interests. Acknowledgments The baseline survey and the first resurvey were supported by a research grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term continuation of the project is supported by programme grants from the UK Wellcome Trust (088158/Z/09/Z, 104085/Z/14/Z), the Chinese Ministry of Science and Technology (2011BAI09B01, 2012–14), and the Chinese National Natural Science Foundation (81390541). The British Heart Foundation (BHF), UK Medical Research Council, and Cancer Research UK provide core funding to the Clinical Trial Service Unit, University of Oxford, UK. FB acknowledges support from the BHF Centre of Research Excellence, Oxford. The chief acknowledgment is to the participants, the project staff, and the China National Centre for Disease Control and Prevention (CDC) and its regional offices for access to death and disease registries. The Chinese National Health Insurance scheme provided electronic linkage to all hospital admission data.Funding
In this Chinese population, usual blood pressure was positively and log-linearly associated with risk of ischaemic heart disease, ischaemic stroke, intracerebral haemorrhage, and the aggregate of all major vascular diseases. These relationships continued down to at least 120 mm Hg systolic blood pressure and 75 mm Hg diastolic blood pressure, below which the evidence was scarce. The associations attenuated with increasing age, but even at ages 70–79 years there were strong associations with each of the main types of vascular disease. At all ages, there were steeper associations between blood pressure and intracerebral haemorrhage than ischaemic stroke. We estimated that about half of all premature vascular deaths were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg). Our study showed stronger associations between blood pressure and vascular disease than have previous prospective studies in China, largely because those studies did not correct for within-person variability in blood pressure (regression dilution bias). 21–23 Compared with previous large meta-analyses of prospective studies that corrected for regression dilution (the Prospective Studies Collaboration 4 and the Asia Pacific Cohort Studies Collaboration 5 ), the findings are consistent for ischaemic heart disease but differ somewhat for stroke types. By contrast with these meta-analyses, our study found strong evidence that, throughout middle age and into old age, there were steeper associations for intracerebral haemorrhage than ischaemic stroke. These differences might, in part, reflect the high rate of brain imaging in this study. The use of brain imaging for diagnosis of stroke types was less common before the mid-1990s and, hence, it is possible that there was substantial misclassification of stroke types in some of the older studies included in these meta-analyses. By contrast, brain imaging was used to diagnose stroke types in about 90% of stroke cases in the CKB study. The greater use of brain imaging might also have allowed more non-fatal strokes to be identified than previously. There were shallower associations for non-fatal than fatal ischaemic stroke (unlike for intracerebral haemorrhage), and there is some evidence that both case fatality and the strength of associations with blood pressure might differ between the different aetiological subtypes of ischaemic stroke (large-artery atherosclerosis, small-vessel disease, cardioembolism, or other pathology). 8,24 Information on subtypes of ischaemic stroke is not yet available in the present study, but small-vessel (lacunar) infarcts, with low case fatality, might well be more common in Chinese than white populations. 25 Randomised controlled trials 6,26 of blood-pressure-lowering medication have shown the reversibility of some of the excess vascular risks associated with elevated blood pressure. A comparison of the findings from blood-pressure-lowering trials with the predicted effects of blood pressure from prospective cohort studies suggests that about 60% of the predicted risks of ischaemic heart disease and 80% of the predicted risks of stroke were reversed within 4–5 years of initiating treatment. 26 Furthermore, the trial results indicate that the proportional effects of blood pressure on vascular risk were similar among people with and without cardiovascular disease, so the absolute benefits are very much greater among those with existing disease. 6 Similarly, the absolute benefits of blood pressure lowering are likely to be greater in older than younger adults, given the greater absolute risk of vascular disease at older age. Guidelines on the management of hypertension generally recommend initiating treatment in adults with an average systolic blood pressure of 140 mm Hg or more, or diastolic blood pressure of 90 mm Hg or more, and some recent randomised trials, in selected populations, have found benefit in initiating treatment at lower levels. 27,28 However, the use of blood-pressure-lowering treatment in China is much lower than in western populations. 29 Our previous analyses of the CKB study indicate that, consistent with nationally representative surveys in China, 30,31 about a third of adults had hypertension at baseline (defined as systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mm Hg, or receiving treatment for hypertension). 32 Of those with hypertension, about a third were diagnosed; of those diagnosed, about half were treated; and, of those treated, about a third had their hypertension controlled. The result was that less than 5% of participants with hypertension achieved properly controlled blood pressure. Previous studies reported associations between blood pressure variability and risk of vascular disease independently of baseline systolic blood pressure, 33,34 but there were an insufficient number of repeat blood pressure measures to assess any such effects in this study. However, other studies have suggested that, after correction for regression dilution bias in blood pressure variability, the effects of any such variability in systolic blood pressure on risk of vascular diseases, independent of usual levels of systolic blood pressure, are likely to be modest. 35 We observed significant positive associations between systolic blood pressure and chronic kidney disease and diabetes, but the causal relevance of these associations remains uncertain. Neither association is strongly supported by evidence from trials, and might well be accounted for by reverse causality or residual confounding. A large meta-analysis 6 of randomised controlled trials of blood-pressure-lowering medications reported that lowering blood pressure had no significant effect on the incidence of renal failure (10 mm Hg lower systolic blood pressure was associated with RR 0·95 [95% CI 0·84–1·07]). However, renal failure might not be entirely consistent with chronic kidney disease as defined in this study (the level of renal impairment among incident chronic kidney disease cases was not available). For diabetes, there is some evidence from randomised trials that lower blood pressure is associated with a reduced incidence of diabetes, but the effects are limited to certain medications only (angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers), indicating that the renin–angiotensin system might be causally related to diabetes rather than actual levels of blood pressure. 36 The chief strengths of this study include the large number of disease events, high-quality measurements of blood pressure (including the training of technicians), and long-term follow-up of a wide range of clinically validated disease outcomes. The main findings support efforts to address the substantial burden of blood pressure on vascular disease in China, and indicate that even small reductions in mean blood pressure at a population level can have a substantial effect on disease risk: for example, 5 mm Hg lower usual blood pressure would prevent around 350 000 deaths per year among individuals younger than 80 years of age (and around 200 000 deaths at <70 years). The use of blood-pressure-lowering medication is low in China, and strategies to improve rates of awareness, detection, and treatment of individuals with hypertension are likely to be highly cost-effective, especially among those with existing vascular disease. 37 In the absence of well developed primary care systems, population-based approaches are also required to address the major determinants of elevated blood pressure in China, including high sodium intake (eg, through salt reduction), high alcohol consumption, excess adiposity, lack of regular physical activity, and poor home heating in winter. 38–40 In conclusion, among men and women in China, higher levels of blood pressure were continuously and positively associated with higher risks of major vascular disease, with no evidence of a threshold down to at least 120 mm Hg systolic blood pressure and 75 mm Hg diastolic blood pressure. Unlike studies in western populations, blood pressure was more strongly associated with intracerebral haemorrhage than ischaemic stroke. There was also evidence of positive associations with some non-vascular chronic diseases, but the causality of these associations remains unclear. It was estimated that about half of all vascular deaths in China were attributable to elevated blood pressure, accounting for roughly 1 million deaths (age <80 years) annually; given the strength of the associations between blood pressure and vascular disease, even small reductions in mean blood pressure at a population level would be expected to have a major impact on vascular morbidity and mortality. Contributors BL, SL, RCl, ZC, and LL designed and planned the paper; BL, XLK, SL, RCl, ZC, and LL were involved in data analysis, interpretation, and reporting; BL, SL, RCl, ZC, and LL were involved in manuscript drafting; RCl, ZC, LL, RP, RCo, RGW, YG, and JC, as members of China Kadoorie Biobank steering committee, designed and supervised the overall conduct of the study and obtained funding. YG, YC, ZB, and ZC coordinated the data acquisition (for baseline surveys, resurveys, and long-term follow-up). All authors provided critical comments on the manuscript. Declaration of interests We declare no competing interests. Acknowledgments The baseline survey and the first resurvey were supported by a research grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term continuation of the project is supported by programme grants from the UK Wellcome Trust (088158/Z/09/Z, 104085/Z/14/Z), the Chinese Ministry of Science and Technology (2011BAI09B01, 2012–14), and the Chinese National Natural Science Foundation (81390541). The British Heart Foundation (BHF), UK Medical Research Council, and Cancer Research UK provide core funding to the Clinical Trial Service Unit, University of Oxford, UK. FB acknowledges support from the BHF Centre of Research Excellence, Oxford. The chief acknowledgment is to the participants, the project staff, and the China National Centre for Disease Control and Prevention (CDC) and its regional offices for access to death and disease registries. The Chinese National Health Insurance scheme provided electronic linkage to all hospital admission data.
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
ASJC Scopus subject areas
- General Medicine
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