Lewis H Kuller

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (806)5400.27 Total impact

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    ABSTRACT: Background: Vitamin D deficiency has been linked with dementia risk, cognitive decline, and executive dysfunction. However, the association with memory remains largely unknown. Objective: To investigate whether low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with memory decline. Methods: We used data on 1,291 participants from the US Cardiovascular Health Study (CHS) and 915 participants from the Dutch Longitudinal Aging Study Amsterdam (LASA) who were dementia-free at baseline, had valid vitamin D measurements, and follow-up memory assessments. The Benton Visual Retention Test (in the CHS) and Rey's Auditory Verbal Learning Test (in the LASA) were used to assess visual and verbal memory, respectively. Results: In the CHS, those moderately and severely deficient in serum 25(OH)D changed -0.03 SD (95% CI: -0.06 to 0.01) and -0.10 SD (95% CI: -0.19 to -0.02) per year respectively in visual memory compared to those sufficient (p = 0.02). In the LASA, moderate and severe deficiency in serum 25(OH)D was associated with a mean change of 0.01 SD (95% CI: -0.01 to 0.02) and -0.01 SD (95% CI: -0.04 to 0.02) per year respectively in verbal memory compared to sufficiency (p = 0.34). Conclusions: Our findings suggest an association between severe vitamin D deficiency and visual memory decline but no association with verbal memory decline. They warrant further investigation in prospective studies assessing different memory subtypes.
    No preview · Article · Feb 2016 · Journal of Alzheimer's disease: JAD
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    ABSTRACT: Importance Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with no known cause. Case studies primarily of athletes and several case-control studies have suggested that high levels of strenuous physical activity (PA) may increase the risk for ALS. This relationship has yet to be evaluated among women in population-based cohort studies.Objective To evaluate the relationship between PA and risk for ALS mortality in a large cohort of postmenopausal women.Design, Setting, and Participants The Women’s Health Initiative (WHI) enrolled 161 809 postmenopausal women, aged 50 to 79 years (mean [SD] age, 63.6 [7.24] years), between 1993 and 1998 into either a clinical trial or an observational study at 40 clinical research centers across the United States. We conducted a cohort study from November 2014 to September 2015 using baseline and mortality data during an average of 9.6 years of follow-up from the entire WHI cohort, through September 1, 2013 (with 1.1% lost to follow-up), to address whether there is a relationship between PA and ALS mortality.Exposures The WHI assessed frequency and duration of mild, moderate, and strenuous PA at baseline via self-administered questionnaire.Main Outcomes and Measures Underlying cause of death from ALS collected from death certificates.Results The WHI enrolled 161 809 women, of whom 165 died of ALS; women who died of ALS were older (median age, 66 years; interquartile range, 61-69 years) compared with the total WHI study population (median age, 63 years; interquartile range, 57-69 years). Age-adjusted ALS mortality rates varied from 7.4 (95% CI, 5.5-9.9)/100 000 person-years for no strenuous PA to 10.6 (95% CI, 5.6-20.0)/100 000 person-years for strenuous PA 3 or more days per week (P = .07). Adjusted for age and body mass index (calculated as weight in kilograms divided by height in meters squared), the odds ratio for death from ALS for participants with strenuous PA 3 or more days per week compared with no reported strenuous PA was 1.56 (95% CI, 1.02-2.37; P = .04).Conclusions and Relevance To our knowledge, this is the first cohort study to report an increased risk for ALS mortality associated with strenuous PA in postmenopausal women. The association between strenuous PA and ALS risk observed does not compromise the overall benefit of strenuous PA for total mortality, coronary heart disease, and breast cancer reported in other WHI investigations, but it may provide an important clue to the etiology of ALS, if replicated by other studies.
    No preview · Article · Jan 2016
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    ABSTRACT: Background: This post hoc analysis determined if the Women's Health Initiative (WHI) Diet Modification intervention (DM-I) resulted in a significantly different rate of incident hypertension (HTN), as well as longitudinal changes in blood pressure. Methods: Participants were 48,835 postmenopausal women aged 50-79 years who were randomly assigned to either the intervention or comparison group. HTN was defined as self-report of treated HTN collected semiannually or blood pressure ≥140/90mm Hg at one of the annual follow-up clinic visits. Results: After a mean follow-up of 8.3 years, and among those who did not have HTN at baseline (n = 31,146), there were 16,174 (51.9%) HTN cases and those assigned to the intervention group had a 4% lower overall risk of developing incident HTN (hazard ratio (HR): 0.96, 95% confidence interval (CI): 0.93-0.99). Although the risk of HTN was lower in the DM-I group in the first few years, the HR became greater than 1 after year 5 (P-trend < 0.01). Similarly, randomization to the DM-I arm resulted in a small but significantly lower average systolic blood pressure (SBP) at 1 year of follow-up (-0.66mm Hg, 0.44-0.89) that increased over the following 8 years (0.16mm Hg/year, 0.11-0.21), such that any early benefit was eliminated by year 5 and a minimal deleterious effect emerged by year 7. Conclusion: Randomization to an intensive behavioral dietary modification program aimed at a lower total fat intake is not associated with sustained reductions in blood pressure or risk of HTN in postmenopausal women. Clinical trial registration: url http://www.clinicaltrials.gov, unique identifier nct00000611.
    No preview · Article · Dec 2015 · American Journal of Hypertension
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    ABSTRACT: Objective: To examine whether tissue factor pathway inhibitor or acquired activated protein C (APC) resistance influences the increased risk of coronary heart disease (CHD) due to estrogen plus progestin therapy. Approach and results: Prospective nested case-control study of 205 cases of CHD and 481 matched controls in the Women's Health Initiative randomized trial of estrogen plus progestin therapy. After multivariable covariate adjustment, both baseline tissue factor pathway activity (P=0.01) and APC resistance (P=0.004) were associated positively with CHD risk. Baseline tissue factor pathway activity and APC resistance singly or jointly did not significantly modify the effect of estrogen plus progestin on CHD risk. Compared with placebo, estrogen plus progestin decreased tissue factor pathway inhibitor activity and increased APC resistance but these changes did not seem to modify or mediate the effect of estrogen plus progestin on CHD risk. Conclusions: Tissue factor pathway inhibitor activity and APC resistance are related to CHD risk in women, but may not explain the increased CHD risk due to estrogen plus progestin therapy. The data from this study do not support the clinical use of measuring these hemostatic factors to help stratify risk before hormone therapy. Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
    No preview · Article · Dec 2015 · Arteriosclerosis Thrombosis and Vascular Biology
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    ABSTRACT: Objective: We sought to evaluate the cardiovascular impact of coding variants in the apolipoprotein L1 gene APOL1 that protect against trypanosome infection but have been associated with kidney disease among African Americans. Approach and results: As part of the Cardiovascular Health Study, a population-based cohort of Americans aged ≥65 years, we genotyped APOL1 polymorphisms rs73885319 and rs71785153 and examined kidney function, subclinical atherosclerosis, and incident cardiovascular disease and death over 13 years of follow-up among 91 African Americans with 2 risk alleles, 707 other African Americans, and 4964 white participants. The high-risk genotype with 2 risk alleles was associated with 2-fold higher levels of albuminuria and lower ankle-brachial indices but similar carotid intima-media thickness among African Americans. Median survival among high-risk African Americans was 9.9 years (95% confidence interval [CI], 8.7-11.9), compared with 13.6 years (95% CI, 12.5-14.3) among other African Americans and 13.3 years (95% CI, 13.0-13.6) among whites (P=0.03). The high-risk genotype was also associated with increased risk for incident myocardial infarction (adjusted hazard ratio 1.8; 95% CI, 1.1-3.0) and mortality (adjusted hazard ratio 1.3; 95% CI 1.0-1.7). Albuminuria and risk for myocardial infarction and mortality were nearly identical between African Americans with 0 to 1 risk alleles and whites. Conclusions: APOL1 genotype is associated with albuminuria, subclinical atherosclerosis, incident myocardial infarction, and mortality in older African Americans. African Americans without 2 risk alleles do not differ significantly in risk of myocardial infarction or mortality from whites. APOL1 trypanolytic variants may account for a substantial proportion of the excess risk of chronic disease in African Americans.
    No preview · Article · Dec 2015 · Arteriosclerosis Thrombosis and Vascular Biology
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    ABSTRACT: Although Westernized lifestyle was associated with increased coronary heart disease (CHD) morbidity and mortality in first and second generation Japanese Americans; CHD mortality was reported to be lower in them than whites. Risk profile of CHD for third and fourth generation Japanese Americans is not known. We compared progression of CIMT between third or fourth generation Japanese Americans and whites.
    No preview · Article · Dec 2015 · The Canadian journal of cardiology
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    ABSTRACT: Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women's Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p<0.001), and of several site-specific cancers (HR, 1.2-1.4, and up to over 2-fold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p<0.001). There was no overall difference in cancer incidence by diabetes therapy (p=0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 versus 1.45; p=0.007) and for breast cancer (HRs, 0.50 versus 1.29; p=0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · International Journal of Cancer
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    ABSTRACT: Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed.
    No preview · Article · Nov 2015 · Contemporary clinical trials
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    ABSTRACT: Background: -Increasingly, the diagnostic codes from administrative claims data are being used as clinical outcomes. Methods and results: -Data from the Cardiovascular Health Study (CHS) were used to compare event rates and risk-factor associations between adjudicated hospitalized cardiovascular events and claims-based methods of defining events. The outcomes of myocardial infarction (MI), stroke, and heart failure (HF) were defined in three ways: 1) the CHS adjudicated event (CHS[adj]); 2) selected ICD9 diagnostic codes only in the primary position for Medicare claims data from the Center for Medicare and Medicaid Services (CMS[1(st)]); and 3) the same selected diagnostic codes in any position (CMS[any]). Conventional claims-based methods of defining events had high positive predictive values (PPVs) but low sensitivities. For instance, the PPV of an ICD9 code of 410.x1 for a new acute MI in the first position was 90.6%, but this code identified only 53.8% of incident MIs. The observed event rates were low. For MI, the incidence was 14.9 events per 1000 person years for CHS[adj] MI, 8.6 for CMS[1(st)] and 12.2 for CMS[any]. In general, CVD risk factor associations were similar across the three methods of defining events. Indeed, traditional CVD risk factors were also associated with all first hospitalizations not due to an MI. Conclusions: -The use of diagnostic codes from claims data as clinical events, especially when restricted to primary diagnoses, leads to an underestimation of event rates. Additionally, claims-based events data represent a composite endpoint that includes the outcome of interest and selected (misclassified) non-event hospitalizations.
    No preview · Article · Nov 2015 · Circulation
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    Lewis H. Kuller

    Preview · Article · Nov 2015 · EBioMedicine
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    ABSTRACT: Introduction: Increasing life expectancy has resulted in a larger population of older individuals at risk of dementia. Methods: The Cardiovascular Health Study-Cognition Study followed 532 participants from 1998-99 (mean age 79) to 2013 (mean age 93) for death and dementia. Results: Risk of death was determined by extent of coronary artery calcium, high-sensitivity cardiac troponin, brain natriuretic peptide, and white matter grade. Significant predictors of dementia were age, apolipoprotein-E4, vocabulary raw score, hippocampal volume, ventricular size, cognitive performance, and number of blocks walked. By 2013, 160 of 532 were alive, including 19 cognitively normal. Those with normal cognition had higher grade education, better cognition test scores, greater hippocampal volume, faster gait speed, and number of blocks walked as compared with survivors who were demented. Discussion: Few survived free of dementia and disability. Prevention and delay of cognitive decline for this older population is an imperative.
    No preview · Article · Oct 2015 · Alzheimer's & dementia: the journal of the Alzheimer's Association
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    ABSTRACT: Background: There is controversy regarding whether to report concentrations of high-sensitivity cardiac troponin T (hs-cTnT) to the limit of blank (LOB) (3 ng/L) or the limit of detection (LOD) (5 ng/L) of the assay in community-based cohorts. We hypothesized that hs-cTnT concentrations between the LOB and LOD would be associated with poorer cardiovascular outcomes compared to concentrations below the LOB. Methods: hs-cTnT was analyzed in a total of 10 723 participants from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into 2 groups, those with hs-cTnT concentrations below the limit of blank (LOB) (<3 ng/L) and those with hs-cTnT between the LOB and limit of detection (LOD) (3-4.99 ng/L). Cross-sectional associations with traditional cardiovascular risk factors and cardiac structural measurements, and longitudinal associations with long-term cardiovascular outcomes of incident heart failure and cardiovascular death, were determined. Results: Participants with hs-cTnT between the LOB and LOD for all 3 cohorts were older and more likely to be male and have a higher burden of cardiovascular risk factors and structural pathology. A metaanalysis of the 3 cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset heart failure (hazard ratio, 1.18; 95% CI, 1.02-1.38) and cardiovascular mortality (hazard ratio, 1.29; 95% CI, 1.06-1.57). Conclusions: hs-cTnT concentrations between the LOB and LOD (3-4.99 ng/L) are associated with a higher prevalence of traditional risk factors, more cardiac pathology, and worse outcomes than concentrations below the LOB (<3 ng/L).
    No preview · Article · Oct 2015 · Clinical Chemistry
  • Lewis H Kuller
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    ABSTRACT: Twenty-five years ago, on the 75th anniversary of the Johns Hopkins Bloomberg School of Public Health, I noted that epidemiologic research was moving away from the traditional approaches used to investigate "epidemics" and their close relationship with preventive medicine. Twenty-five years later, the role of epidemiology as an important contribution to human population research, preventive medicine, and public health is under substantial pressure because of the emphasis on "big data," phenomenology, and personalized medical therapies. Epidemiology is the study of epidemics. The primary role of epidemiology is to identify the epidemics and parameters of interest of host, agent, and environment and to generate and test hypotheses in search of causal pathways. Almost all diseases have a specific distribution in relation to time, place, and person and specific "causes" with high effect sizes. Epidemiology then uses such information to develop interventions and test (through clinical trials and natural experiments) their efficacy and effectiveness. Epidemiology is dependent on new technologies to evaluate improved measurements of host (genomics), epigenetics, identification of agents (metabolomics, proteomics), new technology to evaluate both physical and social environment, and modern methods of data collection. Epidemiology does poorly in studying anything other than epidemics and collections of numerators and denominators without specific hypotheses even with improved statistical methodologies.
    No preview · Article · Oct 2015 · American journal of epidemiology

  • No preview · Article · Oct 2015 · Arthritis and Rheumatology
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    ABSTRACT: Introduction: The American Heart Association's "Simple 7" offers a practical public health conceptualization of cardiovascular health (CVH). CVH predicts incident cardiovascular disease (CVD) in younger populations, but has not been studied in a large, diverse population of aging postmenopausal women. The extent to which CVH predicts cancer in postmenopausal women is unknown. Methods: Multivariable Cox regression estimated hazard ratios and 95% CIs for the association between CVH and incident CVD, any cancer, and cancer subtypes (lung, colorectal, and breast) among 161,809 Women's Health Initiative observational study and clinical trial participants followed from 1993 through 2010. Data were analyzed in 2013. CVH score was characterized as the number (0 [worst] to 7 [best]) of the American Heart Association's ideal CVH behaviors and factors at baseline: smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and fasting glucose. Results: Median follow-up was approximately 13 years. Fewer minorities and less educated women achieved ideal CVH, a common benchmark. In adjusted models, compared with women with the highest (best) CVH scores, those with the lowest (worst) CVH scores had nearly seven times the hazard of incident CVD (6.83, 95% CI=5.83, 8.00) and 52% greater risk of incident cancer (1.52, 95% CI=1.35, 1.72). Ideal CVH was most strongly inversely associated with lung cancer, then colorectal cancer, and then breast cancer. Conclusions: Lower ideal CVH is more common among minority and less educated postmenopausal women and predicts increased risk of CVD and cancer in this population, emphasizing the importance of prevention efforts among vulnerable older adults.
    No preview · Article · Oct 2015 · American journal of preventive medicine
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    ABSTRACT: Production of very low-density lipoprotein (VLDL) is increased in states of metabolic syndrome, leading to hypertriglyceridemia. However, metabolic syndrome is often associated with non-alcoholic fatty liver disease, which leads to liver fibrosis and inflammation that may decrease VLDL production. In this study, we aim to determine the interactive impact on VLDL profiles from insulin resistance, impairment in liver synthetic function and inflammation.
    No preview · Article · Oct 2015
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    ABSTRACT: Alzheimer disease is the most common form of dementia in the elderly, and the complex relationships among risk factors produce highly variable natural histories from normal cognition through the prodromal stage of mild cognitive impairment (MCI) to clinical dementia. We used a novel statistical approach, mixed membership trajectory models, to capture the variety of such pathways in 652 participants in the Cardiovascular Health Study Cognition Study over 22 years of follow-up (1992-2014). We identified 3 trajectories: a "healthy" profile with a peak probability of MCI between 95 and 100 years of age and only a 50% probability of dementia by age 100; an "intermediate" profile with a peak probability of MCI between 85 and 90 years of age and progression to dementia between 90 and 95 years; and an "unhealthy" profile with a peak probability of progressing to MCI between ages 75 and 80 years and to dementia between the ages of 80 and 85 years. Hypertension, education, race, and the ϵ4 allele of the apolipoprotein E gene all affected the closeness of an individual to 1 or more of the canonical trajectories. These results provide new insights into the natural history of Alzheimer disease and evidence for a potential difference in the pathophysiology of the development of dementia. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Jul 2015 · American journal of epidemiology
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    ABSTRACT: The Seven Countries Study in the 1960s showed very low mortality from coronary heart disease (CHD) in Japan, which was attributed to very low levels of total cholesterol. Studies of migrant Japanese to the USA in the 1970s documented increase in CHD rates, thus CHD mortality in Japan was expected to increase as their lifestyle became Westernized, yet CHD mortality has continued to decline since 1970. This study describes trends in CHD mortality and its risk factors since 1980 in Japan, contrasting those in other selected developed countries. We selected Australia, Canada, France, Japan, Spain, Sweden, the UK and the USA. CHD mortality between 1980 and 2007 was obtained from WHO Statistical Information System. National data on traditional risk factors during the same period were obtained from literature and national surveys. Age-adjusted CHD mortality continuously declined between 1980 and 2007 in all these countries. The decline was accompanied by a constant fall in total cholesterol except Japan where total cholesterol continuously rose. In the birth cohort of individuals currently aged 50-69 years, levels of total cholesterol have been higher in Japan than in the USA, yet CHD mortality in Japan remained the lowest: > 67% lower in men and > 75% lower in women compared with the USA. The direction and magnitude of changes in other risk factors were generally similar between Japan and the other countries. Decline in CHD mortality despite a continuous rise in total cholesterol is unique. The observation may suggest some protective factors unique to Japanese. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
    No preview · Article · Jul 2015 · International Journal of Epidemiology
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    ABSTRACT: The literature on environment and obesity is characterized by studies that are often cross-sectional and lack racial diversity. This study examined associations between neighborhood features and BMI development over 6 years in an urban sample of 2,295 girls (56% African American; mean age at baseline, 11.2 years) in 2004. Analyses were conducted in 2011-2015. Girls, caregivers, and study staff completed annual neighborhood questionnaires. Linear mixed-effects modeling examined annual changes in neighborhood features and BMI and assessed whether baseline neighborhood features modified BMI growth over time. At baseline, 40% of participants were overweight/obese. Participants' neighborhoods had few neighborhood problems, moderate levels of safety issues and inconvenient features, low levels of neighborhood disorder, few cases of loitering youth, and substantial traffic volume. Adverse neighborhood features were more common for African American than white participants. Neighborhood features were relatively stable over the follow-up period. African American girls with helpful neighbors had lower annual BMI growth (-0.09 kg/m(2)) than others. For white girls, BMI increased more for girls with helpful neighbors (+0.09 kg/m(2) annually). Regardless of race, living in a U.S. Census tract with low levels of educational achievement was linked with higher BMI growth (an additional 0.07 kg/m(2) annually). Girls living in Census tracts with high (versus low) levels of poverty gained an additional 0.08 kg/m(2) gain annually. Social environment features are associated with BMI change in white and African American urban girls and may be helpful for identifying girls at risk for early adolescent weight gain. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2015 · American journal of preventive medicine
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    ABSTRACT: 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.
    No preview · Article · Jul 2015 · JAMA The Journal of the American Medical Association

Publication Stats

45k Citations
5,400.27 Total Impact Points


  • 1975-2016
    • University of Pittsburgh
      • • Graduate School of Public Health
      • • Department of Epidemiology
      • • Department of Medicine
      • • Department of Neurological Surgery
      • • Department of Psychiatry
      Pittsburgh, Pennsylvania, United States
  • 2003-2015
    • Beth Israel Deaconess Medical Center
      • Division of General Medicine and Primary Care
      Boston, Massachusetts, United States
    • Kent State University
      Кент, Ohio, United States
  • 2013
    • Wake Forest University
      • Department of Internal Medicine
      Winston-Salem, North Carolina, United States
  • 2011
    • Case Western Reserve University School of Medicine
      • Department of Epidemiology and Biostatistics
      Cleveland, Ohio, United States
  • 1987-2010
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2002-2009
    • University of Vermont
      • Department of Pathology
      Burlington, VT, United States
  • 1995-2008
    • Graduate School USA
      Washington, Washington, D.C., United States
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 2007
    • University of California, Los Angeles
      • Department of Epidemiology
      Los Angeles, CA, United States
    • University of North Carolina at Chapel Hill
      North Carolina, United States
  • 2006
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
    • University at Buffalo, The State University of New York
      • Department of Social and Preventive Medicine
      Buffalo, NY, United States
  • 2004-2006
    • Johns Hopkins University
      • Department of Mental Health
      Baltimore, Maryland, United States
    • University of Washington Seattle
      Seattle, Washington, United States
    • Saint Louis University
      Сент-Луис, Michigan, United States
    • New England Baptist Hospital
      Boston, Massachusetts, United States
  • 2005
    • Harvard University
      • Department of Nutrition
      Cambridge, Massachusetts, United States
  • 2003-2004
    • University of Helsinki
      • Department of Psychology
      Helsinki, Province of Southern Finland, Finland
  • 2000
    • University of California, San Francisco
      San Francisco, California, United States
  • 1997
    • University of California, Irvine
      Irvine, California, United States
  • 1991-1997
    • Western Psychiatric Institute and Clinic
      Pittsburgh, Pennsylvania, United States
  • 1996
    • University of Benin Teaching Hospital
      Benim, Edo, Nigeria
    • Magee-Womens Hospital
      Pittsburgh, Pennsylvania, United States
  • 1994
    • Royal Victorian Eye and Ear Hospital
      Melbourne, Victoria, Australia
    • Fred Hutchinson Cancer Research Center
      Seattle, Washington, United States
    • University of Alabama at Birmingham
      • Department of Medicine
      Birmingham, AL, United States
  • 1991-1992
    • Childrens Hospital of Pittsburgh
      • Department of Pediatrics
      Pittsburgh, Pennsylvania, United States
  • 1990
    • National Institutes of Health
      • Office of Disease Prevention
      Bethesda, MD, United States
  • 1986
    • Georgia Health Sciences University
      • Department of Medicine
      Augusta, Georgia, United States
  • 1984
    • University of California, Davis
      • School of Medicine
      Davis, California, United States
    • Rutgers New Jersey Medical School
      • Department of Medicine
      Newark, New Jersey, United States