Body-mass index, blood pressure, and cause-specific mortality in India: a prospective cohort study of 500 810 adults

Summary: Background: The association between cause-specific mortality and body-mass index (BMI) has been studied mainly in high-income countries. We investigated the relations between BMI, systolic blood pressure, and mortality in India. Methods: Men and women aged 35 years or older were recruited into a prospective study from the general population in Chennai, India between Jan 1, 1998, and Dec 31, 2001. Participants were interviewed (data collected included age, sex, education, socioeconomic status, medical history, tobacco smoking, and alcohol intake) and measured (height, weight, and blood pressure). Deaths were identified by linkage to Chennai city mortality records and through active surveillance by household visits from trained graduate non-medical fieldworkers. After the baseline survey, households were visited once in 2002–05, then biennially until 2015. During these repeat visits, structured narratives of any deaths that took place before March 31, 2015, were recorded for physician coding. During 2013–14, a random sample of participants was also resurveyed as per baseline to assess long-term variability in systolic blood pressure and BMI. Cox regression (standardised for tobacco, alcohol, and social factors) was used to relate mortality rate ratios (RRs) at ages 35–69 years to systolic blood pressure, BMI, or BMI adjusted for usual systolic blood pressure. Findings: 500 810 participants were recruited. After exclusion of those with chronic disease or incomplete data, 414 746 participants aged 35–69 years (mean 46 [SD 9]; 45% women) remained. At recruitment, mean systolic blood pressure was 127 mm Hg (SD 15), and mean BMI was 23·2 kg/m2 (SD 3·8). Correlations of resurvey and baseline measurements were 0·50 for systolic blood pressure and 0·88 for BMI. Low BMI was strongly associated with poverty, tobacco, and alcohol. Of the 29 519 deaths at ages 35–69 years, the cause was vascular for 14 935 deaths (12 504 cardiac, 1881 stroke, and 550 other). Vascular mortality was strongly associated with systolic blood pressure: RRs per 20 mm Hg increase in usual systolic blood pressure were 2·45 (95% CI 2·16–2·78) for stroke mortality, 1·74 (1·64–1·84) for cardiac mortality, and 1·84 (1·75–1·94) for all vascular mortality. Although BMI strongly affected systolic blood pressure (an increase of about 1 mm Hg per kg/m2) and diabetes prevalence, BMI was little related to cardiac or stroke mortality, with only small excesses even for grade 1 obesity (ie, BMIs of 30·0–35·0 kg/m2). After additional adjustment for usual systolic blood pressure, BMI was inversely related to cardiac and stroke mortality throughout the range 15·0–30·0 kg/m2: when underweight participants (ie, BMI 15·0–18·5 kg/m2) were compared with overweight participants (ie, BMI 25·0–30·0 kg/m2), the blood-pressure-adjusted RR was 1·28 (95% CI 1·20–1·38) for cardiac mortality and 1·46 (1·22–1·73) for stroke mortality. Interpretation: In this South Asian population, BMI was little associated with vascular mortality, even though increased BMI is associated with increased systolic blood pressure, which in turn is associated with increased vascular mortality. Hence, some close correlates of below-average BMI must have important adverse effects, which could be of relevance in all populations. Funding: UK Medical Research Council, British Heart Foundation, Cancer Research UK

Burden of hypertension and associated risks for cardiovascular mortality in Cuba: a prospective cohort study

Summary: Background: In Cuba, hypertension control in primary care has been prioritised as a cost-effective means of addressing premature death from cardiovascular disease. However, there is little evidence from large-scale studies on the prevalence and management of hypertension in Cuba, and no direct evidence of the expected benefit of such efforts on cardiovascular mortality. Methods: In a prospective cohort study, adults in the general population identified via local family medical practices were interviewed between Jan 1, 1996, and Nov 24, 2002, in five areas of Cuba, and a subset of participants were resurveyed between July 14, 2006, and Oct 19, 2008, in one area. During household visits, blood pressure was measured and information obtained on diagnosis and treatment of hypertension. We calculated the prevalence of hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or receiving treatment for hypertension) and the proportion of people with hypertension in whom it was diagnosed, treated, and controlled (systolic blood pressure <140 mm Hg, diastolic blood pressure <90 mm Hg). Deaths were identified through linkage by national identification numbers to the Cuban Public Health Ministry records, to Dec 31, 2016. We used Cox regression analysis to compare cardiovascular mortality between participants with versus without uncontrolled hypertension. Rate ratios (RRs) were used to estimate the fraction of cardiovascular deaths attributable to hypertension. Findings: 146 556 participants were interviewed in the baseline survey in 1996–2002 and 24 345 were interviewed in the resurvey in 2006–08. After exclusion for incomplete data and age outside the range of interest, 136 111 respondents aged 35–79 years (mean age 54 [SD 12] years; 75 947 [56%] women, 60 164 [44%] men) were eligible for inclusion in the analyses. 34% of participants had hypertension. Among these, 67% had a diagnosis of hypertension. 76% of participants with diagnosed hypertension were receiving treatment and blood pressure was controlled in 36% of those people. During 1·7 million person-years of follow-up there were 5707 cardiovascular deaths. In the age groups 35–59, 60–69, and 70–79 years, uncontrolled hypertension at baseline was associated with RRs of 2·15 (95% CI 1·88–2·46), 1·86 (1·69–2·05), and 1·41 (1·32–1·52), respectively, and accounted for around 20% of premature cardiovascular deaths. Interpretation: In this Cuban population, a third of people had hypertension. Although levels of hypertension diagnosis and treatment were commensurate with those in some high-income countries, the proportion of participants whose blood pressure was controlled was low. As well as reducing hypertension prevalence, improvement in blood pressure control among people with diagnosed hypertension is required to prevent premature cardiovascular deaths in Cuba. Funding: Medical Research Council, British Heart Foundation, Cancer Research UK

Smoking and smoking cessation in relation to risk of diabetes in Chinese men and women: a 9-year prospective study of 0·5 million people

Summary: Background: In developed countries, smoking is associated with increased risk of diabetes. Little is known about the association in China, where cigarette consumption has increased (first in urban, then in rural areas) relatively recently. Moreover, uncertainty remains about the effect of smoking cessation on diabetes in China and elsewhere. We aimed to assess the associations of smoking and smoking cessation with risk of incident diabetes among Chinese adults. Methods: The prospective China Kadoorie Biobank enrolled 512 891 adults (59% women) aged 30–79 years during 2004–08 from ten diverse areas (five urban and five rural) across China. Participants were interviewed at study assessment clinics, underwent physical measurements, and had a non-fasting blood sample taken. Participants were separated into four categories according to smoking history: never-smokers, ever-regular smokers, ex-smokers, and occasional smokers. Incident diabetes cases were identified through linkage with diabetes surveillance systems, the national health insurance system, and death registries. All analyses were done separately in men and women and Cox regression was used to yield adjusted hazards ratios (HRs) for diabetes associated with smoking. Findings: 68% (n=134 975) of men ever smoked regularly compared with 3% (n=7811) of women. During 9 years' follow-up, 13 652 new-onset diabetes cases were recorded among 482 589 participants without previous diabetes. Among urban men, smokers had an adjusted HR of 1·18 (95% CI 1·12–1·25) for diabetes. HRs increased with younger age at first smoking regularly (1·12, 1·20, and 1·27 at ≥25 years, 20–24 years, and <20 years, respectively; p for trend=0·00073) and with greater amount smoked (1·11, 1·15, 1·42, and 1·63 for <20, 20–29, 30–39 and ≥40 cigarettes per day; p for trend<0·0001). Among rural men, similar, albeit more modest, associations were seen. Overall, HRs were more extreme at higher levels of adiposity. Among men who stopped by choice, there was no excess risk within 5 years of cessation, contrasting with those who stopped because of illness (0·92 [0·75–1·12] vs 1·42 [1·23–1·63]). Among the few women who ever smoked regularly, the excess risk of diabetes was significant (1·33 [1·20–1·47]). Interpretation: Among Chinese adults, smoking was associated with increased risk of diabetes, with no significant excess risk following voluntary smoking cessation. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Ministry of Science and Technology, National Natural Science Foundation of China, and China Scholarship Council

Adiposity and risk of ischaemic and haemorrhagic stroke in 0·5 million Chinese men and women: a prospective cohort study

Summary: Background: China has high stroke rates despite the population being relatively lean. Uncertainty persists about the relevance of adiposity to risk of stroke types. We aimed to assess the associations of adiposity with incidence of stroke types and effect mediation by blood pressure in Chinese men and women. Methods: The China Kadoorie Biobank enrolled 512 891 adults aged 30–79 years from ten areas (five urban and five rural) during 2004–08. During a median 9 years (IQR 8–10) of follow-up, 32 448 strokes (about 90% confirmed by neuroimaging) were recorded among 489 301 participants without previous cardiovascular disease. Cox regression analysis was used to produce adjusted hazard ratios (HRs) for ischaemic stroke (n=25 210) and intracerebral haemorrhage (n=5380) associated with adiposity. Findings: Mean baseline body-mass index (BMI) was 23·6 kg/m2 (SD 3·2), and 331 723 (67·8%) participants had a BMI of less than 25 kg/m2. Throughout the range examined (mean 17·1 kg/m2 [SD 0·9] to 31·7 kg/m2 [2·0]), each 5 kg/m2 higher BMI was associated with 8·3 mm Hg (SE 0·04) higher systolic blood pressure. BMI was positively associated with ischaemic stroke, with an HR of 1·30 (95% CI 1·28–1·33 per 5 kg/m2 higher BMI), which was generally consistent with that predicted by equivalent differences in systolic blood pressure (1·25 [1·24–1·26]). The HR for intracerebral haemorrhage (1·11 [1·07–1·16] per 5 kg/m2 higher BMI) was less extreme, and much weaker than that predicted by the corresponding difference in systolic blood pressure (1·48 [1·46–1·50]). Other adiposity measures showed similar associations with stroke types. After adjustment for usual systolic blood pressure, the positive associations with ischaemic stroke were attenuated (1·05 [1·03–1·07] per 5 kg/m2 higher BMI); for intracerebral haemorrhage, they were reversed (0·73 [0·70–0·77]). High adiposity (BMI >23 kg/m2) accounted for 14·7% of total stroke (16·5% of ischaemic stroke and 6·7% of intracerebral haemorrhage). Interpretation: In Chinese adults, adiposity was strongly positively associated with ischaemic stroke, chiefly through its effect on blood pressure. For intracerebral haemorrhage, leanness, either per se or through some other factor (or factors), might increase risk, offsetting the protective effects of lower blood pressure. Funding: UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, Chinese National Natural Science Foundation

Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study

Summary: 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