Ben Lacey

Seasonal variation in blood pressure and its relationship with outdoor temperature in 10 diverse regions of China: the China Kadoorie Biobank.

Objectives: Mean blood pressure varies moderately with outdoor air temperature in many western populations. Substantial uncertainty exists, however, about the strength of the relationship in other populations and its relevance to age, adiposity, medical treatment, climate and housing conditions. Methods: To investigate the relationship of blood pressure with season and outdoor temperature, we analysed cross-sectional data from the China Kadoorie Biobank study of 506 673 adults aged 30–79 years recruited from 10 diverse urban and rural regions in China. Analyses related mean blood pressure – overall and in various subgroups – to mean local outdoor temperature. Results: The mean difference in SBP between summer (June–August) and winter (December–February) was 10 mmHg overall, and was more extreme, on average, in rural than in urban areas (12 vs. 8 mmHg; P for interaction <0.0001). Above 5°C, SBP was strongly inversely associated with outdoor temperature in all 10 areas studied, with 5.7 (SE 0.04) mmHg higher SBP per 10°C lower outdoor temperature. The association was stronger in older people and in those with lower BMI. At lower temperatures, there was no evidence of an association among participants who reported having central heating in their homes. Conclusion: Blood pressure was strongly inversely associated with outdoor temperature in Chinese adults across a range of climatic conditions, although access to home central heating appeared to remove much of the association during the winter months. Seasonal variation in blood pressure should be considered in the clinical management of hypertension.

Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease.

Atherosclerosis is a leading cause of vascular disease worldwide. Its major clinical manifestations include ischemic heart disease, ischemic stroke, and peripheral arterial disease. In high-income countries, there have been dramatic declines in the incidence and mortality from ischemic heart disease and ischemic stroke since the middle of the 20th century. For example, in the United Kingdom, the probability of death from vascular disease in middle-aged men (35-69 years) has decreased from 22% in 1950 to 6% in 2010. Most low- and middle-income countries have also reported declines in mortality from stroke over the last few decades, but mortality trends from ischemic heart disease have been more varied, with some countries reporting declines and others reporting increases (particularly those in Eastern Europe and Asia). Many major modifiable risk factors for atherosclerosis have been identified, and the causal relevance of several risk factors is now well established (including, but not limited to, smoking, adiposity, blood pressure, blood cholesterol, and diabetes mellitus). Widespread changes in health behaviors and use of treatments for these risk factors are responsible for some of the dramatic declines in vascular mortality in high-income countries. In order that these declines continue and are mirrored in less wealthy nations, increased efforts are needed to tackle these major risk factors, particularly smoking and the emerging obesity epidemic.

The Burden of Hypertension and Associated Risk for Cardiovascular Mortality in China

IMPORTANCE Hypertension is a leading cause of premature death in China, but limited evidence is available on the prevalence and management of hypertension and its effect on mortality from cardiovascular disease (CVD). OBJECTIVES To examine the prevalence, diagnosis, treatment, and control of hypertension and to assess the CVD mortality attributable to hypertension in China. DESIGN, SETTING AND PARTICIPANTS This prospective cohort study (China Kadoorie Biobank Study) recruited 500 223 adults, aged 35 to 74 years, from the general population in China. Blood pressure (BP) measurements were recorded as part of the baseline survey from June 25, 2004, to August 5, 2009, and 7028 deaths due to CVD were recorded before January 1, 2014 (mean duration of follow-up: 7.2 years). Data were analyzed from June 9, 2014, to July 17, 2015. EXPOSURES Prevalence and diagnosis of hypertension (systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or receiving treatment for hypertension) and treatment and control rates overall and in various population subgroups. MAIN OUTCOMES AND MEASURES Cox regression analysis yielded age- and sex-specific rate ratios for deaths due to CVD comparing participants with and without uncontrolled hypertension, which were used to estimate the number of CVD deaths attributable to hypertension. RESULTS The cohort included 205 167 men (41.0%) and 295 056 women (59.0%) with a mean (SD) age of 52 (10) years for both sexes. Overall, 32.5% of participants had hypertension; the prevalence increased with age (from 12.6% at 35-39 years of age to 58.4% at 70-74 years of age) and varied substantially by region (range, 22.7%-40.7%). Of those with hypertension, 30.5% had received a diagnosis from a physician; of those with a diagnosis of hypertension, 46.4% were being treated; and of those treated, 29.6% had their hypertension controlled (ie, systolic BP <140 mm Hg; diastolic BP <90 mm Hg), resulting in an overall control rate of 4.2%. Even among patients with hypertension and prior CVD, only 13.0% had their hypertension controlled. Uncontrolled hypertension was associated with relative risks for CVD mortality of 4.1 (95% CI, 3.7-4.6), 2.6 (95% CI, 2.4-2.9) and 1.9 (95% CI, 1.8-2.0) at ages 35 to 59, 60 to 69, and 70 to 79 years, respectively, and accounted for about one-third of deaths due to CVD (approximately 750 000) at 35 to 79 years of age in 2010. CONCLUSIONS AND RELEVANCE About one-third of Chinese adults in this national cohort population had hypertension. The levels of diagnosis, treatment, and control were much lower than in Western populations, and were associated with significant excess mortality.

The Role of Emerging Risk Factors in Cardiovascular Outcomes

Purpose of ReviewThis review discusses the recent evidence for a selection of blood-based emerging risk factors, with particular reference to their relation with coronary heart disease and stroke.Recent FindingsFor lipid-related emerging risk factors, recent findings indicate that increasing high-density lipoprotein cholesterol is unlikely to reduce cardiovascular risk, whereas reducing triglyceride-rich lipoproteins and lipoprotein(a) may be beneficial. For inflammatory and hemostatic biomarkers, genetic studies suggest that IL-6 (a pro-inflammatory cytokine) and several coagulation factors are causal for cardiovascular disease, but such studies do not support a causal role for C-reactive protein and fibrinogen. Patients with chronic kidney disease are at high cardiovascular risk with some of this risk not mediated by blood pressure. Randomized evidence (trials or Mendelian) suggests homocysteine and uric acid are unlikely to be key causal mediators of chronic kidney disease-associated risk and sufficiently large trials of interventions which modify mineral bone disease biomarkers are unavailable. Despite not being causally related to cardiovascular disease, there is some evidence that cardiac biomarkers (e.g. troponin) may usefully improve cardiovascular risk scores.SummaryMany blood-based factors are strongly associated with cardiovascular risk. Evidence is accumulating, mainly from genetic studies and clinical trials, on which of these associations are causal. Non-causal risk factors may still have value, however, when added to cardiovascular risk scores. Although much of the burden of vascular disease can be explained by ‘classic’ risk factors (e.g. smoking and blood pressure), studies of blood-based emerging factors have contributed importantly to our understanding of pathophysiological mechanisms of vascular disease, and new targets for potential therapies have been identified.

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.

Systolic Blood Pressure and Vascular Disease in Men Aged 65 Years and Over: The HIMS (Health in Men Study)

There is uncertainty about the relation between blood pressure and vascular disease at older age. We assessed the association of systolic blood pressure (SBP) and major vascular events in a prospective cohort study of 7564 men aged 65 to 94 years, recruited in 1996–1999 from the general population in Perth, Western Australia. SBP was measured at baseline and again at resurvey in 2001–2004. Participants were monitored for fatal and nonfatal vascular events. To limit the effect of reverse causality, analyses were restricted to men without previous vascular disease at baseline. Hazard ratios were estimated by Cox regression, with adjustment for age and education (further adjustment did not materially change the associations). During a mean follow-up of 11 years, there were 1557 major vascular events. Continuous log-linear associations were found between usual SBP and risk of major vascular events throughout the SBP range examined (145–170 mm Hg). Overall, 10 mm Hg higher usual SBP was associated with ≈20% higher risk of major vascular events (hazard ratio, 19%; 95% confidence interval, 13%–26%; mean age at event 80 years). There was evidence of positive associations with both ischemic heart disease and stroke and effect modification by age, with shallower associations at older ages. Even at 85 to 94 years, however, there was evidence of a positive association: 10 mm Hg higher usual SBP was associated with 14% (95% confidence interval, 1%–30%) higher risk of major vascular events.

Body Mass Index and Vascular Disease in Men Aged 65 Years and Over: HIMS (Health In Men Study)

Background Understanding the relationship between body mass index (BMI) and vascular disease at older age has become increasingly important in the many countries where both average age and BMI are rising. Methods and Results In this prospective cohort study, 12 203 men (aged ≥65) were recruited in 1996–1999 from the general population in Perth, Australia. To limit reverse causality, analyses excluded those with past vascular disease and the first 4 years of follow‐up. During a further 8 (SD3) years of follow‐up, there were 1136 first‐ever major vascular events (nonfatal myocardial infarction, nonfatal stroke, or death from any vascular cause). Cox regression (adjusted for age, education, and smoking) related BMI at recruitment to incidence of major vascular events. At ages 65 to 94, the lowest risk of major vascular events was at ≈ 22.5 to 25 kg/m2. In the higher BMI range (≥25 kg/m2), 5 kg/m2 higher BMI was associated with 33% higher risk of major vascular events (hazard ratio, 1.33 [95% confidence interval, 1.18–1.49]): 24% higher risk of ischemic heart disease (1.24 [1.06–1.46]); 34% higher risk of stroke (1.34 [1.11–1.63]); and 78% higher risk of other vascular death (1.78 [1.32–2.41]). In the lower BMI range, there were fewer events and no strong evidence of an association (hazard ratio per 5 kg/m2 higher BMI, 0.82 [95% confidence interval, 0.61–1.12]). Conclusions In this population of older men, risk of major vascular events was lowest at ≈ 22.5 to 25 kg/m2. Above this range, BMI was strongly related to incidence of major vascular events, with each 5 kg/m2 higher BMI associated with ≈30% higher risk.

Systolic Blood Pressure and Vascular Disease in Men Aged 65 Years and Over

There is uncertainty about the relation between blood pressure and vascular disease at older age. We assessed the association of systolic blood pressure (SBP) and major vascular events in a prospective cohort study of 7564 men aged 65 to 94 years, recruited in 1996–1999 from the general population in Perth, Western Australia. SBP was measured at baseline and again at resurvey in 2001–2004. Participants were monitored for fatal and nonfatal vascular events. To limit the effect of reverse causality, analyses were restricted to men without previous vascular disease at baseline. Hazard ratios were estimated by Cox regression, with adjustment for age and education (further adjustment did not materially change the associations). During a mean follow-up of 11 years, there were 1557 major vascular events. Continuous log-linear associations were found between usual SBP and risk of major vascular events throughout the SBP range examined (145–170 mm Hg). Overall, 10 mm Hg higher usual SBP was associated with ≈20% higher risk of major vascular events (hazard ratio, 19%; 95% confidence interval, 13%–26%; mean age at event 80 years). There was evidence of positive associations with both ischemic heart disease and stroke and effect modification by age, with shallower associations at older ages. Even at 85 to 94 years, however, there was evidence of a positive association: 10 mm Hg higher usual SBP was associated with 14% (95% confidence interval, 1%–30%) higher risk of major vascular events.

Systolic Blood Pressure and Vascular Disease in Men Aged 65 Years and OverNovelty and Significance

There is uncertainty about the relation between blood pressure and vascular disease at older age. We assessed the association of systolic blood pressure (SBP) and major vascular events in a prospective cohort study of 7564 men aged 65 to 94 years, recruited in 1996–1999 from the general population in Perth, Western Australia. SBP was measured at baseline and again at resurvey in 2001–2004. Participants were monitored for fatal and nonfatal vascular events. To limit the effect of reverse causality, analyses were restricted to men without previous vascular disease at baseline. Hazard ratios were estimated by Cox regression, with adjustment for age and education (further adjustment did not materially change the associations). During a mean follow-up of 11 years, there were 1557 major vascular events. Continuous log-linear associations were found between usual SBP and risk of major vascular events throughout the SBP range examined (145–170 mm Hg). Overall, 10 mm Hg higher usual SBP was associated with ≈20% higher risk of major vascular events (hazard ratio, 19%; 95% confidence interval, 13%–26%; mean age at event 80 years). There was evidence of positive associations with both ischemic heart disease and stroke and effect modification by age, with shallower associations at older ages. Even at 85 to 94 years, however, there was evidence of a positive association: 10 mm Hg higher usual SBP was associated with 14% (95% confidence interval, 1%–30%) higher risk of major vascular events.

Systolic Blood Pressure and Vascular Disease in Men Aged 65 Years and OverNovelty and Significance: The HIMS (Health in Men Study)

There is uncertainty about the relation between blood pressure and vascular disease at older age. We assessed the association of systolic blood pressure (SBP) and major vascular events in a prospective cohort study of 7564 men aged 65 to 94 years, recruited in 1996–1999 from the general population in Perth, Western Australia. SBP was measured at baseline and again at resurvey in 2001–2004. Participants were monitored for fatal and nonfatal vascular events. To limit the effect of reverse causality, analyses were restricted to men without previous vascular disease at baseline. Hazard ratios were estimated by Cox regression, with adjustment for age and education (further adjustment did not materially change the associations). During a mean follow-up of 11 years, there were 1557 major vascular events. Continuous log-linear associations were found between usual SBP and risk of major vascular events throughout the SBP range examined (145–170 mm Hg). Overall, 10 mm Hg higher usual SBP was associated with ≈20% higher risk of major vascular events (hazard ratio, 19%; 95% confidence interval, 13%–26%; mean age at event 80 years). There was evidence of positive associations with both ischemic heart disease and stroke and effect modification by age, with shallower associations at older ages. Even at 85 to 94 years, however, there was evidence of a positive association: 10 mm Hg higher usual SBP was associated with 14% (95% confidence interval, 1%–30%) higher risk of major vascular events.