Abstract MP27: Weight Change, BMI, and Mortality Among Survivors of Myocardial Infarction: Analysis of Two Prospective US Cohort Studies

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Laila Al-Shaar ◽  
Yanping Li ◽  
Eric Rimm ◽  
JoAnn E Manson ◽  
Frank Hu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Weight Change ◽  
Normal Weight ◽  
Health Study ◽  
Obese Patients ◽  
Cox Models ◽  
Hazard Ratios ◽  
Before And After ◽  
Cvd Mortality

Background: The relation between BMI, weight change and mortality among survivors of Myocardial Infarction (MI) remains controversial, with some studies reporting favorable survival outcomes among overweight and obese patients, as compared to those with normal weight. We aim to examine the relationship between BMI reported shortly before and after MI diagnosis in addition to weight change with all-cause and cardiovascular disease (CVD) mortality among MI survivors. Methods: Using the data from Nurses’ Health Study (NHS) and Health Professionals Follow up Study (HPFS) cohorts, we studied 4278 participants who were free of CVD and cancer before their MI. Weight change (in BMI units) was categorized as loss of (> 4, 2-4, <2-0 (reference)), or gain of (0.1-2, or >2) units. Multivariable Cox models were used to estimate hazard ratios and 95 % confidence interval for mortality across BMI/weight change categories. Results: During up to 36 (NHS) and 28 (HPFS) years of follow-up post-MI, there were 2071 all-cause and 835 CVD deaths. Overweight patients with BMI before or after MI of 25-27.49 kg/m 2 had decreased mortality as compared to normal weight patients (22.5-24.9 kg/m 2 ). All-cause mortality increased progressively with higher BMI. Obese patients (BMI≥30) had the highest risk of CVD mortality (HR=1.35; 95% CI, 1.06-1.73). Among MI patients who had never smoked (N=1484) or were younger than 65 years of age at the time of diagnosis (N=1873), no survival advantage was observed for overweight/obese patients. Compared to stable weight (a BMI reduction of 0-1.99 units) from before to after MI, a reduction of 2-4 or >4 BMI units was associated with increased mortality (HR=1.12; 95% CI, 0.96-1.29 and 1.42; 95% CI, 1.17-1.71 respectively, Figure). Conclusions: We observed a J-shaped association between BMI and mortality among all MI patients, but not among those who had never smoked or were younger than 65 years of age. Weight loss associated with acute MI, potentially related to disease severity, is an important predictor of higher mortality.

Abstract MP35: Physical Activity Before and After Cancer Diagnosis and Total and Cause-Specific Mortality

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Paulette D Chandler ◽  
Deirdre Tobias ◽  
Jule E Buring ◽  
I-Min Lee ◽  
Daniel Chasman ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cancer Diagnosis ◽  
Cancer Mortality ◽  
Total Mortality ◽  
Health Study ◽  
Specific Mortality ◽  
Before And After ◽  
After Cancer ◽  
Cvd Mortality

Background: Given the increased prevalence of cancer survivors in the United States, it is imperative to define risk factors for potential reductions in total and cause-specific mortality. Physical activity (PA) represents a promising target for intervention. Design: We prospectively evaluated PA from questionnaires before and after cancer diagnosis with total and cause-specific mortality among 13,297 subjects diagnosed with invasive cancer combined from the Physicians’ Health Study (PHS) (n=6328), Physicians’ Health Study II (PHS II) (n=912), and Women's Health Study (WHS) (n=6057). WHS and PHS participants were free of baseline cancer; PHS II participants reported no active cancer at baseline. We ascertained PA before and after an incident cancer diagnosis based on reports on repeated follow-up questionnaires. Death was ascertained by medical records and death certificates. Cox regression estimated combined hazard ratios (HRs) of mortality by PA adjusted for age, randomized treatments, BMI, and other lifestyle/demographic factors. We evaluated the interaction between PA before and after cancer diagnosis by comparing PA ≤1 versus ≥2 times/wk. Results: The mean follow-up after cancer diagnosis was 8.0, 7.5, and 5.2 y for WHS, PHS, and PHS II, respectively, during which there were 5623 deaths (WHS, 2164; PHS, 3269; PHS II; 190). Higher PA before cancer diagnosis was associated with significantly lower mortality. Compared with PA ≤ once/wk, the HRs (95% CIs) associated with PA 2-4 and >4 times/wk were 0.87 (0.82-0.93) and 0.88 (0.82-0.94) for total mortality; 0.77 (0.63-0.95) and 0.79 (0.62-0.997) for CVD mortality, and 0.90 (0.83-0.98) and 0.90 (0.83-0.98) for cancer mortality. Higher PA after cancer diagnosis was associated with significantly lower total and cancer mortality and non-significantly lower CVD mortality, with HRs (95% CIs) of 0.65 (0.58-0.72) and 0.66 (0.59-0.73) for total mortality; 0.78 (0.59-1.03) and 0.82 (0.61-1.10) for CVD mortality, and 0.66 (0.57-0.77) and 0.64 (0.55-0.74) for cancer mortality. There was a significant interaction of PA before and after cancer diagnosis for total (p int =0.02) and cancer (p int =0.007) mortality, but not CVD mortality (p int =0.38). Conclusions: Greater PA both before and after cancer diagnosis were significantly associated with lower total and cancer mortality. Higher PA before cancer diagnosis was also associated with lower CVD mortality. PA may be an important target for lower mortality after cancer diagnosis.

scholarly journals Work disability patterns before and after incident acute myocardial infarction and subsequent risk of common mental disorders: A Swedish cohort study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
K. Bokenberger ◽  
S. Rahman ◽  
M. Wang ◽  
M. Vaez ◽  
T. E. Dorner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Mental Disorders ◽  
Work Disability ◽  
Common Mental Disorders ◽  
Depression And Anxiety ◽  
Cox Models ◽  
Hazard Ratios ◽  
Antidepressant Prescription ◽  
Before And After

Abstract This study investigated the extent to which work disability patterns including sickness absence and disability pension (SA/DP) before and after acute myocardial infarction (AMI) were associated with subsequent common mental disorders (CMDs) such as depression and anxiety in AMI patients without previous CMD. Total 11,493 patients 26–64 years with incident AMI during 2008–10 were followed up for CMD (measured as antidepressant prescription) through 2013. Four SA/DP trajectory groups during the 3-years pre-AMI and 1-year post-AMI were identified. Hazard ratios (HRs) with 95% confidence intervals for subsequent CMD were estimated in Cox models. Higher pre-AMI SA/DP annual levels (>1–12 months/year) were associated with 40–60% increased CMD rate than the majority (78%) with low increasing levels (increasing up to 1 month/year). Regarding post-AMI findings, constant high (~25–30 days/month) SA/DP levels within the first 3 months was associated with a 76% higher CMD rate, compared to constant low (0 days/month). A gradually decreasing post-AMI SA/DP pattern over a 12-month period suggested protective influences for CMD (HR = 0.80). This is the first study to demonstrate that pre- and post-AMI work disability patterns are associated with subsequent CMD risk in AMI patients. Work disability patterns should be considered as an indicator of AMI prognosis in terms of CMD risk.

Weight and weight change and risk of atrial fibrillation: the HUNT study

2019 ◽  
Vol 40 (34) ◽  
pp. 2859-2866 ◽  
Author(s):  
Tingting Feng ◽  
Malmo Vegard ◽  
Linn B Strand ◽  
Lars E Laugsand ◽  
Bjørn Mørkedal ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Weight Change ◽  
Normal Weight ◽  
Hazard Ratios ◽  
Hunt Study ◽  
Average Body Mass ◽  
Average Body ◽  
Over Time

Abstract Aims Although obesity has been associated with risk of atrial fibrillation (AF), the associations of long-term obesity, recent obesity, and weight change with AF risk throughout adulthood are uncertain. Methods and results An ambispective cohort study was conducted which included 15 214 individuals. The cohort was created from 2006 to 2008 (the baseline) and was followed for incident AF until 2015. Weight and height were directly measured at baseline. Data on previous weight and height were retrieved retrospectively from measurements conducted 10, 20, and 40 years prior to baseline. Average body mass index (BMI) over time and weight change was calculated. During follow-up, 1149 participants developed AF. The multivariable-adjusted hazard ratios were 1.2 (95% confidence interval 1.0–1.4) for average BMI 25.0–29.9 kg/m2 and 1.6 (1.2–2.0) for average BMI ≥30 kg/m2 when compared with normal weight. The association of average BMI with AF risk was only slightly attenuated after adjustment for most recent BMI. In contrast, current BMI was not strongly associated with the risk of AF after adjustment for average BMI earlier in life. Compared with stable BMI, both loss and gain in BMI were associated with increased AF risk. After adjustment for most recent BMI, the association of BMI gain with AF risk was largely unchanged, while the association of BMI loss with AF risk was weakened. Conclusion Long-term obesity and BMI change are associated with AF risk. Obesity earlier in life and weight gain over time exert cumulative effects on AF development even after accounting for most recent BMI.

scholarly journals Timing of aspirin use in colorectal cancer chemoprevention: a prospective cohort study

2021 ◽  
Author(s):  
Yin Zhang ◽  
Andrew T Chan ◽  
Jeffrey A Meyerhardt ◽  
Edward L Giovannucci
Keyword(s):  
Colorectal Cancer ◽  
Total Duration ◽  
Cancer Chemoprevention ◽  
Health Study ◽  
Average Dose ◽  
Recent Period ◽  
Cox Models ◽  
Hazard Ratios ◽  
Independent Effects

Abstract Background Prior epidemiological and intervention studies have not been able to separate independent effects of dose, timing and duration of aspirin use in colorectal cancer (CRC) chemoprevention. We examined aspirin-based CRC chemoprevention according to timing in the Nurses’ Health Study and Health Professionals Follow-Up Study. Methods The exposures include cumulative average dose and total duration of aspirin use in &gt; 10 years before follow-up started (remote period), and in the immediate 10 years before follow-up started (recent period). Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals for exposures and CRC risk. Results Aspirin use &gt;10 years before follow-up started (HR = 0.88, 95% CI = 0.83 to 0.94) per 5 year increment) and immediate 10 years before follow-up started (HR = 0.90, 95% CI = 0.84 to 0.96) were similarly important in CRC chemoprevention, though a 5-year lag was required for a clear benefit in the recent period. In the remote period, the association was not dose-dependent; compared to &lt; 0.5 standard (325 mg)-dose tablets/week; hazard ratios were HR = 0.78, 95% CI = 0.63 to 0.98, HR = 0.81, 95% CI = 0.72 to 0.91, and HR = 0.74, 95% CI = 0.64 to 0.86 for doses of 0.5 to &lt; 1.5, 1.5 to &lt; 5, ≥5 tablets/week, respectively. However, there was dose dependency in the recent period (with respective HR = 0.91, 95% CI = 0.79 to 1.06; HR = 0.87, 95% CI = 0.77 to 0.98; and HR = 0.76, 95% CI = 0.64 to 0.91). Conclusion A suggestive benefit necessitates at least 6–10 years and most clearly after approximately 10 years since initiation of aspirin. Remote use and use within the previous 10 years both contribute independently to decreased risk, though a lower dose may be required for a benefit with longer term use.

scholarly journals Association of Walnut Consumption with Total and Cause-Specific Mortality and Life Expectancy in U.S. Adults

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2699
Author(s):  
Xiaoran Liu ◽  
Marta Guasch-Ferré ◽  
Deirdre K. Tobias ◽  
Yanping Li
Keyword(s):  
Life Expectancy ◽  
Cox Regression ◽  
Total Mortality ◽  
Health Study ◽  
Hazard Ratios ◽  
Estimate Life Expectancy ◽  
Specific Mortality ◽  
Elder Adults ◽  
Cvd Mortality

Walnut consumption is associated with health benefits. We aimed to (1) examine the association between walnut consumption and mortality and (2) estimate life expectancy in relation to walnut consumption in U.S. adults. We included 67,014 women of the Nurses’ Health Study (1998–2018) and 26,326 men of the Health Professionals Follow-up Study (1998–2018) who were free of cancer, heart disease, and stroke at baseline. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During up to 20 years of follow-up, we documented 30,263 deaths. The hazard ratios for total mortality across categories of walnut intake (servings/week), as compared to non-consumers, were 0.95 (95% confidence interval (CI), 0.91, 0.98) for <1 serving/week, 0.94 (95% CI, 0.89, 0.99) for 1 serving/week, 0.87 (95% CI, 0.82, 0.93) for 2–4 servings/week, and 0.86 (95% CI, 0.79, 0.93) for >=5 servings/week (p for trend <0.0001). A greater life expectancy at age 60 (1.30 years in women and 1.26 years in men) was observed among those who consumed walnuts more than 5 servings/week compared to non-consumers. Higher walnut consumption was associated with a lower risk of total and CVD mortality and a greater gained life expectancy among U.S. elder adults.

scholarly journals Dairy Consumption and 3-Year Risk of Type 2 Diabetes after Myocardial Infarction: A Prospective Analysis in the Alpha Omega Cohort

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3146
Author(s):  
Maria G. Jacobo Cejudo ◽  
Esther Cruijsen ◽  
Christiane Heuser ◽  
Sabita S. Soedamah-Muthu ◽  
Trudy Voortman ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Population Based ◽  
Cox Models ◽  
Dairy Consumption ◽  
Hazard Ratios ◽  
Alpha Omega ◽  
Physician Diagnosis

Population-based studies suggest a role for dairy, especially yogurt, in the prevention of type 2 diabetes (T2D). Whether dairy affects T2D risk after myocardial infarction (MI) is unknown. We examined associations of (types of) dairy with T2D incidence in drug-treated, post-MI patients from the Alpha Omega Cohort. The analysis included 3401 patients (80% men) aged 60–80 y who were free of T2D at baseline (2002–2006). Dairy intakes were assessed using a validated food-frequency questionnaire. Incident T2D was ascertained through self-reported physician diagnosis and/or medication use. Multivariable Cox models were used to calculate Hazard ratios (HRs) and 95% confidence intervals (CI) for T2D with dairy intake in categories and per 1-standard deviation (SD) increment. Most patients consumed dairy, and median intakes were 264 g/d for total dairy, 82 g/d for milk and 41 g/d for yogurt. During 40 months of follow-up (10,714 person-years), 186 patients developed T2D. After adjustment for confounders, including diet, HRs per 1-SD were 1.06 (95% CI 0.91–1.22) for total dairy, 1.02 (0.88–1.18) for milk and 1.04 (0.90–1.20) for yogurt. Associations were also absent for other dairy types and in dairy categories (all p-trend > 0.05). Our findings suggest no major role for dairy consumption in T2D prevention after MI.

scholarly journals Work disability before and after incident myocardial infarction and subsequent common mental disorder

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
K Bokenberger ◽  
S Rahman ◽  
M Wang ◽  
M Vaez ◽  
T E Dorner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Sickness Absence ◽  
Work Disability ◽  
Disability Pension ◽  
Common Mental Disorders ◽  
Common Mental Disorder ◽  
Cox Models ◽  
Hazard Ratios ◽  
Antidepressant Prescription ◽  
Before And After

Abstract Background This study investigated the extent to which work-disability patterns including sickness absence and disability pension (SA/DP) before and after acute myocardial infarction (AMI) were associated with subsequent common mental disorders (CMDs) such as depression and anxiety in AMI patients without previous CMD. Methods A cohort of 11,493 patients aged 26-64 years without previous CMD with incident AMI during 2008-2010 were followed up for CMD measured as antidepressant prescription through 2013. Four SA/DP trajectory groups during the 3 years pre-AMI and 1 year post-AMI were identified. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated in Cox models. Results Higher pre-AMI SA/DP levels (&gt;1-12 months/year), compared to the majority of patients (78%) following low increasing annual levels (increasing up to 1 month/year) of pre-AMI SA/DP, were associated with a 40-60% increased CMD rate. Regarding post-AMI findings, constant high (∼25-30 days/month) and steeply decreasing SA/DP levels within the first 3 months were associated with a 76% and 35% higher CMD rate, respectively, compared to constant low (&lt;1 days/month) levels. Conversely, a gradually decreasing pattern of post-AMI SA/DP over a 12-month period suggested protective influences for CMD (HR = 0.80), even after adjusting for sociodemographic and medical factors. Conclusions This is the first study to demonstrate that pre- and post-AMI work disability patterns are associated with subsequent CMD risk in AMI patients. Work disability patterns should be considered in clinical practice as an indicator of AMI prognosis in terms of CMD risk. Key messages Increasing and high persistent levels of pre-AMI work disability are associated with higher risk of subsequent CMD, while gradually decreasing post-AMI work disability has a favourable CMD prognosis. Pre- and post-AMI patterns of work disability (sickness absence and disability pension) can be a useful marker in terms of CMD prognosis.

Abstract MP61: Body Mass Index and Mortality among Adults with Incident Type Diabetes: Results from Two Prospective US Cohort Studies

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Deirdre K Tobias ◽  
An Pan ◽  
Eric Ding ◽  
Chandra L Jackson ◽  
Eilis J O’Reilly ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Fixed Effects ◽  
Normal Weight ◽  
Health Study ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Never Smokers ◽  
Cvd Mortality

Background: Recent evidence suggests that having normal weight at time of diagnosis of type 2 diabetes (T2D) is associated with an increased risk of premature death, compared to being overweight or obese; these studies were limited in their sample size and ability to adequately address residual confounding by smoking and reverse causation. Objective: To prospectively evaluate the association between body mass index (BMI) at T2D diagnosis and mortality in two large cohorts. Methods: Women and men with incident T2D from the Nurses’ Health Study (1978-2010; N=8,984) and Health Professionals Follow-up Study (1988-2010; N=2,443) were included if they were free of major chronic disease (cardiovascular disease [CVD], cancer) at T2D diagnosis. Participants’ self-reported body weight preceding diagnosis (mean 11 months) and height was used to calculate BMI (kg/m2). Cox proportional hazards models estimated the relative risk (HR) and 95% confidence interval (CI) for mortality across BMI categories. Multivariable models adjusted for age, smoking, baseline comorbidities (high blood pressure, cholesterol), and several other lifestyle factors. Fixed-effects meta-analyses were used to combine individual cohort estimates. Results: In all, 3,119 total deaths were observed over a follow-up of 36 years in women (18.7 deaths/1,000 person-years) and 26 years in men (25.2 deaths/1,000 person-years). A J-shaped association was observed across BMI categories (18.5-22.4, 22.5-24.9, 25.0-27.4, 27.5-29.9, 30.0-34.9, >35.0) and all-cause mortality (HR [CI] by category: 1.26[1.03, 1.55], 1[reference], 1.11[0.97, 1.28], 1.08[0.94, 1.25], 1.19[1.04, 1.37], 1.33[1.15, 1.55]). After stratifying by smoking status, a direct linear association was present among never smokers and a J-shaped relationship persisted among ever smokers. Excluding deaths in the first 4 years of follow-up and adjusting for BMI change prior to diagnosis further accentuated the linear relationship between BMI and all-cause mortality among never smokers (0.90[0.57, 1.43], 1.00 [reference], 1.19[0.91, 1.57], 1.20[0.91, 1.58], 1.27[0.97, 1.65], 1.50[1.14, 1.99]; p-trend<0.001). The association across BMI categories and CVD mortality was also linear among never smokers, and flat among ever smokers. In addition, among ever smokers, cancer mortality was highest among those with BMI 18.5-22.5. No clear trend was observed between BMI and mortality due to other causes. Excluding insulin users did not appreciably modify the associations. Conclusions: We found no evidence to support lower mortality rates among diabetics who were overweight or obese at diagnosis, compared to their normal-weight counterparts. In contrast, after accounting for confounding by smoking, we observed direct linear relationships between BMI and both all-cause and CVD mortality in our cohorts. Reducing other biases strengthened these relationships.

Association between selenium intake, diabetes, and mortality in adults: findings from National Health and Nutrition Examination Survey (NHANES) 2003-2014

2021 ◽  
pp. 1-24
Author(s):  
Bushra Hoque ◽  
Zumin Shi
Keyword(s):  
National Health ◽  
Cox Regression ◽  
Inverse Association ◽  
Nutrition Examination Survey ◽  
Health And Nutrition ◽  
Hazard Ratios ◽  
The Us ◽  
All Cause Mortality ◽  
Cvd Mortality

Abstract Selenium (Se) is a trace mineral that has antioxidant and anti-inflammatory properties. This study aimed to investigate the association between Se intake, diabetes, all-cause and cause-specific mortality in a representative sample of US adults. Data from 18,932 adults who attended the 2003-2014 National Health and Nutrition Examination Survey (NHANES) were analysed. Information on mortality was obtained from the US mortality registry updated to 2015. Multivariable logistic regression and Cox regression were used. Cross-sectionally, Se intake was positively associated with diabetes. Comparing extreme quartiles of Se intake, the odds ratio (OR) for diabetes was 1.44 (95% CI: 1.09–1.89). During a mean of 6.6 years follow-up, there were 1627 death (312 CVD, 386 cancer). High intake of Se was associated with a lower risk of all-cause mortality. When comparing the highest with the lowest quartiles of Se intake, the hazard ratios (HRs) for all-cause, CVD mortality, cancer mortality and other mortality were: 0.77 (95% CI 0.59-1.01), 0.62 (95% CI, 0.35-1.13), 1.42 (95% CI, 0.78-2.58) and 0.60 (95% CI,0.40-0.80), respectively. The inverse association between Se intake and all-cause mortality was only found among white participants. In conclusion, Se intake was positively associated with diabetes but inversely associated with all-cause mortality. There was no interaction between Se intake and diabetes in relation to all-cause mortality.

Abstract 052: Short-acting Hypnotic Drugs Increase Mortality and Obese Patients are Particularly Vulnerable

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Robert D Langer ◽  
Daniel F Kripke ◽  
Lawrence E Kline
Keyword(s):  
Excess Mortality ◽  
Poor Sleep ◽  
Obese Patients ◽  
Cox Models ◽  
Short Acting ◽  
Hypnotic Drug ◽  
Hazard Ratios ◽  
Levels Of Use ◽  
Low Levels ◽  
Hypnotic Drugs

Background: An estimated 6% – 10% of U.S. adults took a hypnotic drug for poor sleep in 2010. At least 18 studies have reported significant (p<0.05) associations of hypnotic usage with increased mortality. However, most lacked data on newer, supposedly safer, short-acting drugs, and had limited control for confounding by health status. Furthermore, little is known regarding potentially heightened risks in specific vulnerable populations. Objective: The present study was designed to test whether newer short-acting hypnotic drugs were associated with increased mortality after controlling for comorbid conditions, and to assess risks within subgroups of patients with specific medical conditions. Methods: Using electronic medical records from a large U.S. health system the authors conducted a one-to-two matched-cohort survival analysis of associations between hypnotic drug use and mortality. Records were extracted for 10,529 hypnotic users and 23,676 matched controls with no hypnotic prescriptions, mean age 54 years, followed for an average of 2.5 years between 2002 and 2006. Hazard ratios (HR) for death were computed from Cox models controlled for risk factors and stratified on comorbidites. Results: The short-acting drugs zolpidem (41%) and temazapam (20%) accounted for the majority of use. Patients prescribed any hypnotic had substantially elevated hazards of dying compared to non-users. Importantly, the death hazard was evident even in the lowest tertile, 1 to 18 pills per year, HR 3.60 (95% Confidence Interval, 2.92 – 4.44). HRs for the remaining tertiles were 4.43 (3.67 – 5.36) and 5.32 (4.50 – 6.30), demonstrating a dose-response association. HR were robust within subgroups restricted to users and non-users with identical comorbidity, implying that selective use of hypnotics by patients in poor health was an unlikely explanation for the excess mortality. Obesity emerged as a marker of increased vulnerability. Among 2206 patients with a diagnosis of obesity, (mean BMI 38.8), the mortality HRs by hypnotic tertile were 8.07 (3.64 – 17.89), 6.37 (2.73 – 14.88), and 9.34 (4.47 – 19.52). Additional models were fitted for patients with the combination of Obesity + Diabetes + Hypertension to evaluate the possibility that this risk was driven by metabolic syndrome. HRs for that combination were slightly lower than those for obesity alone, suggesting that obesity was the primary factor. Conclusions: Short-acting hypnotics were associated with a more than 3-fold increased hazard of death that, even at low levels of use. Obese patients appear particularly vulnerable, perhaps through interaction with sleep apnea. Emerging evidence for substantial harm, even with limited exposure to hypnotics, should be weighed against any benefits.

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