Annals of Epidemiology 24 (2014) 362e368
Contents lists available at ScienceDirect
Annals of Epidemiology journal homepage: www.annalsofepidemiology.org
Original article
Diabetes predicts long-term disability in an elderly urban cohort: the Northern Manhattan Study Mandip S. Dhamoon MD, MPH a, *, Yeseon Park Moon MS b, Myunghee C. Paik PhD b, Ralph L. Sacco MD, MS c, d, e, Mitchell S.V. Elkind MD, MS f a
Department of Neurology, Mount Sinai School of Medicine, New York, NY Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY Department of Neurology, Evelyn F. McKnight Brain Institute, Miller School of Medicine, University of Miami, FL d Department of Public Health Sciences and Human Genetics, Miller School of Medicine, University of Miami, FL e Department of Human Genetics, Miller School of Medicine, University of Miami, FL f Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 20 August 2013 Accepted 24 December 2013 Available online 3 January 2014
Purpose: There are limited data on vascular predictors of long-term disability in Hispanics. We hypothesized that (1) functional status declines over time and (2) vascular risk factors predict functional decline. Methods: The Northern Manhattan Study contains a population-based study of 3298 stroke-free individuals aged 40 years or older, followed for median 11 years. The Barthel Index (BI) was assessed annually. Generalized estimating equations and Cox models were adjusted for demographic, medical, and social risk factors. Stroke and myocardial infarction occurring during follow-up were censored in sensitivity analysis. Secondarily, motor and nonmotor domains of the BI were analyzed. Results: Mean age (standard deviation) of the cohort (n ¼ 3298) was 69.2 (10) years, 37% were male, 52% Hispanic, 22% diabetic, and 74% hypertensive. There was a mean annual decline of 1.02 BI points (P < .0001). Predictors of decline in BI included age, female sex, diabetes, depression, and normocholesterolemia. Results did not change with censoring. We found similar predictors of BI for motor and nonmotor domains. Conclusion: In this large, population-based, multiethnic study with long-term follow-up, we found a 1% mean decline in function per year that did not change when vascular events were censored. Diabetes predicted functional decline in the absence of clinical vascular events. Ó 2014 Elsevier Inc. All rights reserved.
Keywords: Epidemiology Disability Stroke
Introduction Vascular risk factors lead to disability through multiple mechanisms, including clinical and subclinical cerebrovascular events causing impairment, cardiovascular events causing reduced cardiopulmonary fitness, and nonvascular complications of diabetes such as neuropathy. Diabetes in particular is growing in prevalence, and understanding the population impact of diabetes on disability is increasingly important. Several possible mechanisms link diabetes and disability, including decreased cardiovascular function, neuropathy, sarcopenia, and inflammatory processes [1]. The interplay between diabetes and particular functional limitations has varied in different populations [2]. Previous research on disability in Hispanics, a markedly heterogeneous group in the * Corresponding author. Department of Neurology, Mount Sinai School of Medicine, 1468 Madison Ave, Annenberg 301A, New York, NY 10029. Tel.: 212 241-2252; fax: 212-860-4952. E-mail address: [email protected] (M.S. Dhamoon). 1047-2797/$ e see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.annepidem.2013.12.013
United States with a disproportionate burden of diabetes, has focused on Mexican-Americans [3e5], and relatively little is known about the long-term disability among Caribbean Hispanics [6]. Furthermore, the impact of vascular risk factors may vary based on age subgroups in the elderly. Prior studies have found that age, cognitive function, mood disorders, and social supports consistently predict long-term disability [7e9], and among diseases stroke is the foremost cause [10e12]. However, several questions remain unanswered. First, the relationship between predictors and long-term disability may have been altered by shifts in paradigms of treatment (of cholesterol [13] and blood pressure [14], for example), increasing obesity prevalence, and population patterns of aging. Also, in many studies, vascular events such as stroke or myocardial infarction (MI) and vascular risk factors [15] did not undergo specialist review and adjudication, resulting in misclassification. Third, most studies have examined predictors of average disability instead of trajectories of change. An explicit analysis of trajectories of disability would
M.S. Dhamoon et al. / Annals of Epidemiology 24 (2014) 362e368
distinguish among factors that predict baseline disability, change in function over time, and discrete decrements in function. For this, long-term follow-up and repeated measures of disability are needed. However, most studies have included only hospitalized patients with limited follow-up, and few population-based studies have had long-term follow-up [16]. Finally, there are limited data of the course and predictors of disability in predominantly Hispanic populations [17], especially in urban, elderly cohorts, in whom the burden of comorbid conditions such as obesity, diabetes, and hypertension is high. We sought to address these questions in the population-based Northern Manhattan Study (NOMAS), an ongoing observational study with annual assessment of functional outcomes and specialist adjudication of vascular events. A prior NOMAS study showed a decline in functional status over the long term after stroke, even in the absence of recurrent vascular events [18,19]. However, we had not examined the course and predictors of long-term functional status in a stroke-free cohort. We hypothesized that functional status declines over time and that vascular risk factors predict decline independent of the occurrence of stroke and heart disease. This study adds to previous literature due to its size, predominantly Caribbean Hispanic cohort, population-based sampling, an explicit focus on modeling trajectories of disability, and the use of two complementary modeling strategies to robustly identify predictors and trajectories of disability. Materials and methods NOMAS is a prospective, population-based cohort of 3298 subjects in a community-based sample of a racially and ethnically diverse population. The study was approved by the institutional review boards of Columbia University and the University of Miami, and informed consent was obtained from all participants. Cohort selection The cohort was recruited between 1993 and 2001 [20,21]. Subjects were enrolled if they were aged at least 40 years, lived in a predefined geographic area of northern Manhattan for at least 3 months in a household with a telephone, and did not have prior stroke. Subjects were contacted by random digit dialing of published and unpublished telephone numbers. The telephone response rate was 91%, 87% of eligible subjects indicated willingness to participate, and enrollment response rate was 75%. Baseline assessment Baseline examination included comprehensive medical history, physical examination, medical record review, and fasting blood samples. Standardized questions were adapted from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System. Baseline age was calculated by subtracting the date of birth from date of enrollment. Sex was self-reported as male or female. Race-ethnicity was self-identified and modeled after the U.S. census. Smoking was defined as never, former, and current (within a year). Education was classified as at least versus less than high school education. Marital status was classified as married versus other. Insurance status was characterized as Medicare/private insurance versus Medicaid/no insurance. Hypertension, coded as present or absent, was defined as a systolic blood pressure recording 140 mmHg or higher or a diastolic blood pressure recording 90 mm Hg or higher (based on the average of two blood pressure measurements) or self-report of history of hypertension or antihypertensive use. Diabetes mellitus was defined by self-report, fasting blood glucose level of 126 mg/dL or
363
Table 1 Baseline characteristics of study population Number of participants, no. (%) Demographics Age, mean (SD), y Male, no. (%) Non-Hispanic white, no. (%) Non-Hispanic black, no. (%) Hispanic, no. (%) Other race, no. (%) Highest education achieved, no. (%) 8th grade or less Some high school Completed high school Some college College graduate or higher Marital status, no. (%) Single Married Widowed Divorced Separated Insured with Medicaid or uninsured, no. (%) Insured with Medicare or private insurance, no. (%) Number of friends, no. (%) None 1 or 2 3 or 4 5 or more Baseline BI score, no. (%) 0e60 65e80 85e95 100 Risk factors, no. (%)* Alcohol use, no. (%) Never Past Light Moderate Intermediate Heavy Physical activity, no. (%) None Light Moderate Heavy Hypertension, no. (%) Hypercholesterolemia, no. (%) Diabetes mellitus, no. (%) History of coronary artery disease, no. (%) Depression, no. (%) Hamilton Depression Scale score, no. (%) 0e5 6e10 11e15 16e20 21þ Smoking status, no. (%) Never smoked Past smoking history Current smoking Incident strokes during follow-up, no. *
3298 (100) 69.2 1227 690 803 1726 79
(10.3) (37.2) (20.9) (24.4) (52.3) (2.4)
1313 473 607 397 507
(39.8) (14.4) (18.4) (12.0) (15.4)
523 1042 924 513 294 1435 1841
(15.9) (31.6) (28.0) (15.6) (8.9) (43.8) (56.2)
130 367 653 2145
(4.0) (11.1) (19.8) (65.1)
45 108 608 2532
(1.4) (3.3) (18.5) (76.9)
821 799 421 1086 120 51
(24.9) (24.2) (12.8) (32.9) (3.6) (1.6)
1388 1622 137 145 2429 2050 716 705 336
(42.2) (49.3) (4.2) (4.4) (73.7) (62.2) (21.8) (21.4) (10.2)
2642 456 136 34 17
(80.4) (13.9) (4.1) (1.0) (0.5)
1548 (47.0) 1179 (35.8) 569 (17.3) 330
As defined in text.
higher, or insulin/oral hypoglycemic use. Fasting total cholesterol was obtained using a Hitachi 705 automated spectrophotometer (Boehringer, Mannheim, Germany). Hypercholesterolemia was defined as self-report of hypercholesterolemia, lipid lowering therapy use, or fasting total cholesterol level more than 240 mg/ dL. Alcohol use was defined as low/no (2 drinks/d). Physical activity was assessed using a questionnaire adapted from the National Health Interview Survey and classified as any or none, as in the previous research in this cohort [22,23]. Number of friends
364
M.S. Dhamoon et al. / Annals of Epidemiology 24 (2014) 362e368
Table 2 Predictors of baseline functional status and change over time as measured by the BI, with all variables included in a GEE model Variable
Baseline BI score
Overall change Demographic variables Age (per year) Male sex Race-ethnicityy Black Hispanic At least high school education Insured with Medicaid or uninsured Social variables Married At least three friends Vascular risk factors Diabetes Depression Hypertension History of coronary artery disease Hypercholesterolemia Any physical activity Smoking statusz Past Current Alcohol usex Moderate Heavy * y z x
Compared Compared Compared Compared
with with with with
Change over time in BI score
Difference in baseline BI score*
Standard error
P
Annual change in BI score
Standard error
P
d
d
d
1.43
0.18
Contents lists available at ScienceDirect
Annals of Epidemiology journal homepage: www.annalsofepidemiology.org
Original article
Diabetes predicts long-term disability in an elderly urban cohort: the Northern Manhattan Study Mandip S. Dhamoon MD, MPH a, *, Yeseon Park Moon MS b, Myunghee C. Paik PhD b, Ralph L. Sacco MD, MS c, d, e, Mitchell S.V. Elkind MD, MS f a
Department of Neurology, Mount Sinai School of Medicine, New York, NY Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY Department of Neurology, Evelyn F. McKnight Brain Institute, Miller School of Medicine, University of Miami, FL d Department of Public Health Sciences and Human Genetics, Miller School of Medicine, University of Miami, FL e Department of Human Genetics, Miller School of Medicine, University of Miami, FL f Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 20 August 2013 Accepted 24 December 2013 Available online 3 January 2014
Purpose: There are limited data on vascular predictors of long-term disability in Hispanics. We hypothesized that (1) functional status declines over time and (2) vascular risk factors predict functional decline. Methods: The Northern Manhattan Study contains a population-based study of 3298 stroke-free individuals aged 40 years or older, followed for median 11 years. The Barthel Index (BI) was assessed annually. Generalized estimating equations and Cox models were adjusted for demographic, medical, and social risk factors. Stroke and myocardial infarction occurring during follow-up were censored in sensitivity analysis. Secondarily, motor and nonmotor domains of the BI were analyzed. Results: Mean age (standard deviation) of the cohort (n ¼ 3298) was 69.2 (10) years, 37% were male, 52% Hispanic, 22% diabetic, and 74% hypertensive. There was a mean annual decline of 1.02 BI points (P < .0001). Predictors of decline in BI included age, female sex, diabetes, depression, and normocholesterolemia. Results did not change with censoring. We found similar predictors of BI for motor and nonmotor domains. Conclusion: In this large, population-based, multiethnic study with long-term follow-up, we found a 1% mean decline in function per year that did not change when vascular events were censored. Diabetes predicted functional decline in the absence of clinical vascular events. Ó 2014 Elsevier Inc. All rights reserved.
Keywords: Epidemiology Disability Stroke
Introduction Vascular risk factors lead to disability through multiple mechanisms, including clinical and subclinical cerebrovascular events causing impairment, cardiovascular events causing reduced cardiopulmonary fitness, and nonvascular complications of diabetes such as neuropathy. Diabetes in particular is growing in prevalence, and understanding the population impact of diabetes on disability is increasingly important. Several possible mechanisms link diabetes and disability, including decreased cardiovascular function, neuropathy, sarcopenia, and inflammatory processes [1]. The interplay between diabetes and particular functional limitations has varied in different populations [2]. Previous research on disability in Hispanics, a markedly heterogeneous group in the * Corresponding author. Department of Neurology, Mount Sinai School of Medicine, 1468 Madison Ave, Annenberg 301A, New York, NY 10029. Tel.: 212 241-2252; fax: 212-860-4952. E-mail address: [email protected] (M.S. Dhamoon). 1047-2797/$ e see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.annepidem.2013.12.013
United States with a disproportionate burden of diabetes, has focused on Mexican-Americans [3e5], and relatively little is known about the long-term disability among Caribbean Hispanics [6]. Furthermore, the impact of vascular risk factors may vary based on age subgroups in the elderly. Prior studies have found that age, cognitive function, mood disorders, and social supports consistently predict long-term disability [7e9], and among diseases stroke is the foremost cause [10e12]. However, several questions remain unanswered. First, the relationship between predictors and long-term disability may have been altered by shifts in paradigms of treatment (of cholesterol [13] and blood pressure [14], for example), increasing obesity prevalence, and population patterns of aging. Also, in many studies, vascular events such as stroke or myocardial infarction (MI) and vascular risk factors [15] did not undergo specialist review and adjudication, resulting in misclassification. Third, most studies have examined predictors of average disability instead of trajectories of change. An explicit analysis of trajectories of disability would
M.S. Dhamoon et al. / Annals of Epidemiology 24 (2014) 362e368
distinguish among factors that predict baseline disability, change in function over time, and discrete decrements in function. For this, long-term follow-up and repeated measures of disability are needed. However, most studies have included only hospitalized patients with limited follow-up, and few population-based studies have had long-term follow-up [16]. Finally, there are limited data of the course and predictors of disability in predominantly Hispanic populations [17], especially in urban, elderly cohorts, in whom the burden of comorbid conditions such as obesity, diabetes, and hypertension is high. We sought to address these questions in the population-based Northern Manhattan Study (NOMAS), an ongoing observational study with annual assessment of functional outcomes and specialist adjudication of vascular events. A prior NOMAS study showed a decline in functional status over the long term after stroke, even in the absence of recurrent vascular events [18,19]. However, we had not examined the course and predictors of long-term functional status in a stroke-free cohort. We hypothesized that functional status declines over time and that vascular risk factors predict decline independent of the occurrence of stroke and heart disease. This study adds to previous literature due to its size, predominantly Caribbean Hispanic cohort, population-based sampling, an explicit focus on modeling trajectories of disability, and the use of two complementary modeling strategies to robustly identify predictors and trajectories of disability. Materials and methods NOMAS is a prospective, population-based cohort of 3298 subjects in a community-based sample of a racially and ethnically diverse population. The study was approved by the institutional review boards of Columbia University and the University of Miami, and informed consent was obtained from all participants. Cohort selection The cohort was recruited between 1993 and 2001 [20,21]. Subjects were enrolled if they were aged at least 40 years, lived in a predefined geographic area of northern Manhattan for at least 3 months in a household with a telephone, and did not have prior stroke. Subjects were contacted by random digit dialing of published and unpublished telephone numbers. The telephone response rate was 91%, 87% of eligible subjects indicated willingness to participate, and enrollment response rate was 75%. Baseline assessment Baseline examination included comprehensive medical history, physical examination, medical record review, and fasting blood samples. Standardized questions were adapted from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System. Baseline age was calculated by subtracting the date of birth from date of enrollment. Sex was self-reported as male or female. Race-ethnicity was self-identified and modeled after the U.S. census. Smoking was defined as never, former, and current (within a year). Education was classified as at least versus less than high school education. Marital status was classified as married versus other. Insurance status was characterized as Medicare/private insurance versus Medicaid/no insurance. Hypertension, coded as present or absent, was defined as a systolic blood pressure recording 140 mmHg or higher or a diastolic blood pressure recording 90 mm Hg or higher (based on the average of two blood pressure measurements) or self-report of history of hypertension or antihypertensive use. Diabetes mellitus was defined by self-report, fasting blood glucose level of 126 mg/dL or
363
Table 1 Baseline characteristics of study population Number of participants, no. (%) Demographics Age, mean (SD), y Male, no. (%) Non-Hispanic white, no. (%) Non-Hispanic black, no. (%) Hispanic, no. (%) Other race, no. (%) Highest education achieved, no. (%) 8th grade or less Some high school Completed high school Some college College graduate or higher Marital status, no. (%) Single Married Widowed Divorced Separated Insured with Medicaid or uninsured, no. (%) Insured with Medicare or private insurance, no. (%) Number of friends, no. (%) None 1 or 2 3 or 4 5 or more Baseline BI score, no. (%) 0e60 65e80 85e95 100 Risk factors, no. (%)* Alcohol use, no. (%) Never Past Light Moderate Intermediate Heavy Physical activity, no. (%) None Light Moderate Heavy Hypertension, no. (%) Hypercholesterolemia, no. (%) Diabetes mellitus, no. (%) History of coronary artery disease, no. (%) Depression, no. (%) Hamilton Depression Scale score, no. (%) 0e5 6e10 11e15 16e20 21þ Smoking status, no. (%) Never smoked Past smoking history Current smoking Incident strokes during follow-up, no. *
3298 (100) 69.2 1227 690 803 1726 79
(10.3) (37.2) (20.9) (24.4) (52.3) (2.4)
1313 473 607 397 507
(39.8) (14.4) (18.4) (12.0) (15.4)
523 1042 924 513 294 1435 1841
(15.9) (31.6) (28.0) (15.6) (8.9) (43.8) (56.2)
130 367 653 2145
(4.0) (11.1) (19.8) (65.1)
45 108 608 2532
(1.4) (3.3) (18.5) (76.9)
821 799 421 1086 120 51
(24.9) (24.2) (12.8) (32.9) (3.6) (1.6)
1388 1622 137 145 2429 2050 716 705 336
(42.2) (49.3) (4.2) (4.4) (73.7) (62.2) (21.8) (21.4) (10.2)
2642 456 136 34 17
(80.4) (13.9) (4.1) (1.0) (0.5)
1548 (47.0) 1179 (35.8) 569 (17.3) 330
As defined in text.
higher, or insulin/oral hypoglycemic use. Fasting total cholesterol was obtained using a Hitachi 705 automated spectrophotometer (Boehringer, Mannheim, Germany). Hypercholesterolemia was defined as self-report of hypercholesterolemia, lipid lowering therapy use, or fasting total cholesterol level more than 240 mg/ dL. Alcohol use was defined as low/no (2 drinks/d). Physical activity was assessed using a questionnaire adapted from the National Health Interview Survey and classified as any or none, as in the previous research in this cohort [22,23]. Number of friends
364
M.S. Dhamoon et al. / Annals of Epidemiology 24 (2014) 362e368
Table 2 Predictors of baseline functional status and change over time as measured by the BI, with all variables included in a GEE model Variable
Baseline BI score
Overall change Demographic variables Age (per year) Male sex Race-ethnicityy Black Hispanic At least high school education Insured with Medicaid or uninsured Social variables Married At least three friends Vascular risk factors Diabetes Depression Hypertension History of coronary artery disease Hypercholesterolemia Any physical activity Smoking statusz Past Current Alcohol usex Moderate Heavy * y z x
Compared Compared Compared Compared
with with with with
Change over time in BI score
Difference in baseline BI score*
Standard error
P
Annual change in BI score
Standard error
P
d
d
d
1.43
0.18
