The prevalence of cardiometabolic multimorbidity is increasing.
To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.
Age- and sex-adjusted mortality rates and ...hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates.
A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).
All-cause mortality and estimated reductions in life expectancy.
In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.
Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
Smoking and consuming alcohol are both related to increased mortality risk. Their combined effects on cause-specific mortality were investigated in a prospective cohort study.
Participants were 5771 ...men aged 35-64, recruited during 1970-73 from various workplaces in Scotland. Data were obtained from a questionnaire and a screening examination. Causes of death were all cause, coronary heart disease (CHD), stroke, alcohol-related, respiratory and smoking-related cancer. Participants were divided into nine groups according to their smoking status (never, ex or current) and reported weekly drinking (none, 1-14 units and 15 or more). Cox proportional hazards models were used to obtain relative rates of mortality, adjusted for age and other risk factors.
In 30 years of follow-up, 3083 men (53.4%) died. Compared with never smokers who did not drink, men who both smoked and drank 15+ units/week had the highest all-cause mortality (relative rate = 2.71 (95% confidence interval 2.31-3.19)). Relative rates for CHD mortality were high for current smokers, with a possible protective effect of some alcohol consumption in never smokers. Stroke mortality increased with both smoking and alcohol consumption. Smoking affected respiratory mortality with little effect of alcohol. Adjusting for a wide range of confounders attenuated the relative rates but the effects of alcohol and smoking still remained. Premature mortality was particularly high in smokers who drank 15 or more units, with a quarter of the men not surviving to age 65. 30% of men with manual occupations both smoked and drank 15+ units/week compared with only 13% with non-manual ones.
Smoking and drinking 15+ units/week was the riskiest behaviour for all causes of death.
Studies suggest a J-shaped association between blood pressure and cardiovascular events in the setting of intensive systolic blood pressure control; whether there is a similar association with stroke ...remains less well established. The Secondary Prevention of Small Subcortical Strokes was a randomized trial to evaluate higher (130-149 mm Hg) versus lower (<130 mm Hg) systolic blood pressure targets in participants with recent lacunar infarcts. We evaluated the association of mean achieved blood pressure, 6 months after randomization, and recurrent stroke, major vascular events, and all-cause mortality. After a mean follow up of 3.7 years, there was a J-shaped association between achieved blood pressure and outcomes; the lowest risk was at ≈124 and 67 mm Hg systolic and diastolic blood pressure, respectively. For example, above a systolic blood pressure of 124 mm Hg, 1 standard deviation higher (11.1 mm Hg) was associated with increased mortality (adjusted hazard ratio: 1.9; 95% confidence interval: 1.4, 2.7), whereas below this level, this relationship was inverted (0.29; 0.10, 0.79), P<0.001 for interaction. Above a diastolic blood pressure of 67 mm Hg, a 1 standard deviation higher (8.2 mm Hg) was associated with an increased risk of stroke (2.2; 1.4, 3.6), whereas below this level, the association was in the opposite direction (0.34; 0.13, 0.89), P=0.02 for interaction. The lowest risk of all events occurred at a nadir of ≈120 to 128 mm Hg systolic blood pressure and 65 to 70 mm Hg diastolic blood pressure. Future studies should evaluate the impact of excessive blood pressure reduction, especially in older populations with preexisting vascular disease.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.
To describe the effect of atrial fibrillation on long-term morbidity and mortality.
The Renfrew/Paisley Study surveyed 7052 men and 8354 women aged 45-64 years between 1972 and 1976. All ...hospitalizations and deaths occurring during the subsequent 20 years were analyzed by the presence or absence of atrial fibrillation at baseline. Lone atrial fibrillation was defined in the absence of other cardiovascular signs or symptoms. Cox proportional hazards models were used to adjust for age and cardiovascular conditions.
After 20 years, 42 (89%) of the 47 women with atrial fibrillation had a cardiovascular event (death or hospitalization), compared with 2276 (27%) of the 8307 women without this arrhythmia. Among men, 35 (66%) of 53 with atrial fibrillation had an event, compared with 3151 (45%) of 6999 without atrial fibrillation. In women, atrial fibrillation was an independent predictor of cardiovascular events (rate ratio RR = 3.0; 95% confidence interval CI: 2.1-4.2), fatal or nonfatal strokes (RR = 3.2; 95% CI: 1.0-5.0), and heart failure (RR = 3.4; 95% CI: 1.9-6.2). The rate ratios among men were 1.8 (95% CI: 1.3-2.5) for cardiovascular events, 2.5 (95% CI: 1.3-4.8) for strokes, and 3.4 (95% CI: 1.7-6.8) for heart failure. Atrial fibrillation was an independent predictor of all-cause mortality in women (RR = 2.2; 95% CI: 1.5-3.2) and men (RR = 1.5; 95% CI: 1.2-2.2). However, lone atrial fibrillation (which occurred in 15 subjects) was not associated with a statistically significant increase in either cardiovascular events (RR = 1.5; 95% CI: 0.6-3.6) or mortality (RR = 1.8; 95% CI: 0.9-3.8).
Atrial fibrillation is associated with an increased long-term risk of stroke, heart failure, and all-cause mortality, especially in women.
Background: Air pollution-mortality risk estimates are generally larger at longer-term, compared with short-term, exposure time scales. Objective: We compared associations between short-term exposure ...to black smoke (BS) and mortality with long-term exposure—mortality associations in cohort participants and with short-term exposure-mortality associations in the general population from which the cohorts were selected. Methods: We assessed short-to-medium-term exposure-mortality associations in the Renfrew-Paisley and Collaborative cohorts (using nested case-control data sets), and compared them with long-term exposure-mortality associations (using a multilevel spatiotemporal exposure model and survival analyses) and short-to-medium-term exposure-mortality associations in the general population (using time-series analyses). Results: For the Renfrew-Paisley cohort (15,331 participants), BS exposure-mortality associations were observed in nested case—control analyses that accounted for spatial variations in pollution exposure and individual-level risk factors. These cohort-based associations were consistently greater than associations estimated in time-series analyses using a single monitoring site to represent general population exposure {e.g., 1.8% 95% confidence interval (CI): 0.1, 3.4% vs. 0.2% (95% CI: 0.0, 0.4%) increases in mortality associated with 10-μg/m³ increases in 3-day lag BS, respectively}. Exposure-mortality associations were of larger magnitude for longer exposure periods e.g., 3.4% (95% CI: -0.7, 7.7%) and 0.9% (95% CI: 0.3, 1.5%) increases in all-cause mortality associated with 10-μg/m³ increases in 31-day BS in case—control and time-series analyses, respectively; and 10% (95% CI: 4, 17%) increase in all-cause mortality associated with a 10-μg/m³ increase in geometic mean BS for 1970-1979, in survival analysis. Conclusions: After adjusting for individual-level exposure and potential confounders, short-term exposure—mortality associations in cohort participants were of greater magnitude than in comparable general population time-series study analyses. However, short-term exposure-mortality associations were substantially lower than equivalent long-term associations, which is consistent with the possibility of larger, more persistent cumulative effects from long-term exposures.
Background
Small subcortical strokes, also known as lacunar strokes, comprise more than 25% of brain infarcts, and the underlying vasculopathy is the most common cause of vascular cognitive ...impairment. How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear. The aim of the Secondary Prevention of Small Subcortical Strokes study (Trial registration: NCT00059306) is to define strategies for reducing stroke recurrence, cognitive decline, and major vascular events.
Methods
Secondary Prevention of Small Subcortical Strokes is a randomised, multicentre clinical trial (n=3000) being conducted in seven countries, and sponsored by the US NINDS/NIH. Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously randomised, in a 2 × 2 factorial design, to antiplatelet therapy – 325 mg aspirin daily plus 75 mg clopidogrel daily, vs. 325 mg aspirin daily plus placebo, double-blind – and to one of two levels of systolic blood pressure targets –‘intensive’ (<130 mmHg) vs. ‘usual’ (130–149 mmHg). Participants are followed for an average of four-years. Time to recurrent stroke (ischaemic or haemorrhagic) is the primary outcome and will be analysed separately for each intervention. The secondary outcomes are the rate of cognitive decline and major vascular events. The primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.
Conclusions
Secondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infarcts, which are likely due to small vessel disease. The results will inform the management of millions of patients with this common vascular disorder.
Objective To investigate whether alcohol consumption and raised body mass index (BMI) act together to increase risk of liver disease.Design Analysis of data from prospective cohort studies.Setting ...Scotland.Participants Data were from two of the Midspan prospective cohort studies (9559 men): “Main” study 1965-8, participants from workplaces across central belt of Scotland, population of island of Tiree, and mainland relatives, and “Collaborative” study, 1970-3, participants from 27 workplaces in Glasgow, Clydebank, and Grangemouth. Follow-up was to 31 December 2007 (median 29 years, range 0.13-42). We divided participants into nine groups based on measures of body mass index (BMI) (underweight/normal weight <25, overweight 25 to <30, and obese ≥30) and alcohol consumption (none, 1-14, and ≥15 units per week).Main outcome measures Liver disease morbidity and mortality.Results 80 (0.8%) men died with liver disease as the main cause and 146 (1.5%) with liver disease as any cause. In the Collaborative study, 196 men (3.3%) had liver disease defined by a death, admission, or cancer registration. BMI and alcohol consumption were strongly associated with liver disease mortality in analyses adjusted for other confounders (P=0.001 and P<0.0001 respectively). Drinkers of 15 or more units per week in any BMI category and obese drinkers had raised relative rates for all definitions of liver disease, compared with underweight/normal weight non-drinkers. Drinkers of 15 or more units per week had adjusted relative rates for liver disease mortality of 3.16 (95% confidence interval 1.28 to 7.8) for underweight/normal weight men, 7.01 (3.02 to 16.3) for overweight, and 18.9 (6.84 to 52.4) for obese men. The relative rate for obese men who consumed 1-14 units per week was 5.3 (1.36 to 20.7). The relative excess risk due to interaction between BMI and alcohol consumption was 5.58 (1.09 to 10.1); synergy index=2.89 (1.29 to 6.47).Conclusions Raised BMI and alcohol consumption are both related to liver disease, with evidence of a supra-additive interaction between the two. The occurrence of both factors in the same populations should inform health promotion and public health policies.
Objective: To examine the effect of reverse causality and confounding on the association of BMI with all‐cause and cause‐specific mortality.
Research Methods and Procedures: Data from two large ...prospective studies were used. One (a community‐based cohort) included 8327 women and 7017 men who resided in two Scottish towns at the time of the baseline assessment in 1972–1976; the other (an occupational cohort) included 4016 men working in the central belt of Scotland at the time of the baseline assessment in 1970–1973. Participants in both cohorts were ages 45 to 64 years at baseline; the follow‐up period was 28 to 34 years.
Results: In age‐adjusted analyses that did not take account of reverse causality or smoking, there was no association between being overweight (BMI 25 to <30 kg/m2) and mortality, and weak to modest associations between obesity (BMI ≥30 kg/m2) and mortality. There was a strong association between smoking and lower BMI in women and men in both cohorts (all p < 0.0001). Among never‐smokers and with the first 5 years of deaths removed, overweight was associated with an increase in all‐cause mortality (relative risk ranging from 1.12 to 1.38), and obesity was associated with a doubling of risk in men in both cohorts (relative risk, 2.10 and 1.96, respectively) and a 60% increase in women (relative risk, 1.56). In both never‐smokers and current smokers, being overweight or obese was associated with important increases in the risk of cardiovascular disease.
Discussion: These findings demonstrate that with appropriate control for smoking and reverse causality, both overweight and obesity are associated with important increases in all‐cause and cause‐specific mortality, and in particular with cardiovascular disease mortality.
ABSTRACT
Aims To investigate the relationships between alcohol consumption and mortality and morbidity risk by specific causes.
Design Prospective cohort study.
Setting Twenty‐seven work‐places in ...West and Central Scotland.
Participants A total of 6000 men aged 21–64 years at screening in 1970–1973, median follow‐up 29 years.
Measurements Relative rates, using Cox's proportional hazard models, by weekly reported units of alcohol consumption for all cause, coronary heart disease (CHD), stroke, respiratory, digestive, liver disease and alcohol‐related causes of mortality and for specific causes of acute hospital admissions.
Findings Mortality risk was increased for men drinking 15–21 or more units per week for all causes, stroke, liver disease and alcohol‐related causes. For respiratory mortality, drinkers of 35 or more units had double the risk compared to non‐drinkers. CHD mortality showed increasing trends with consumption when adjusted for age and after full adjustment showed no clear patterns, although the 8–14 units group had a lower risk than non‐drinkers relative rate 0.81 (0.68–0.97). Hospital admissions had similar patterns to mortality for stroke and liver disease. Increased risk began at 8–14 units for alcohol‐related admissions, and at 15–21 units for respiratory admissions. Non‐drinkers had higher risks of having a CHD admission than drinkers and there were decreasing trends with increasing consumption (P = 0.019).
Conclusions Consumption of 15–21 units per week and over was associated with increased mortality from most causes and increased risk of hospital admissions from stroke, liver disease and respiratory diseases. Alcohol‐related admissions were raised from 8 to 14 units. Alcohol use may have been under‐reported in our study, but it was similar to other studies of the time. The apparent protective effect of alcohol with CHD admissions could be due partly to detrimental effects of heavy drinking causing sudden deaths. The associations, including that with respiratory disease, may arise from inadequate adjustment for confounding by other factors such as smoking.
Objective To assess the impact of tobacco smoking on the survival of men and women in different social positions.Design A cohort observational study.Setting Renfrew and Paisley, two towns in west ...central Scotland.Participants 8353 women and 7049 men aged 45-64 years recruited in 1972-6 (almost 80% of the population in this age group). The cohort was divided into 24 groups by sex (male, female), smoking status (current, former, or never smokers), and social class (classes I + II, III non-manual, III manual, and IV + V) or deprivation category of place of residence.Main outcome measure Relative mortality (adjusted for age and other risk factors) in the different groups; Kaplan-Meier survival curves and survival rates at 28 years.Results Of those with complete data, 4387/7988 women and 4891/6967 men died over the 28 years. Compared with women in social classes I + II who had never smoked (the group with lowest mortality), the adjusted relative mortality of smoking groups ranged from 1.7 (95% confidence interval 1.3 to 2.3) to 4.2 (3.3 to 5.5). Former smokers’ mortalities were closer to those of never smokers than those of smokers. By social class (highest first), age adjusted survival rates after 28 years were 65%, 57%, 53%, and 56% for female never smokers; 41%, 42%, 33%, and 35% for female current smokers; 53%, 47%, 38%, and 36% for male never smokers; and 24%, 24%, 19%, and 18% for male current smokers. Analysis by deprivation category gave similar results.Conclusions Among both women and men, never smokers had much better survival rates than smokers in all social positions. Smoking itself was a greater source of health inequality than social position and nullified women’s survival advantage over men. This suggests the scope for reducing health inequalities related to social position in this and similar populations is limited unless many smokers in lower social positions stop smoking.
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