|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2002; 40:954-960 © 2002 by the American College of Cardiology Foundation |
* Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts, USA
Department of Nutrition, Boston, Massachusetts, USA
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
Manuscript received December 4, 2001; revised manuscript received May 7, 2002, accepted May 24, 2002.
* Reprint requests and correspondence: Dr. Eunyoung Cho, Channing Laboratory, 181 Longwood Avenue, Boston, Massachusetts 02115, USA
Eunyoung.Cho{at}channing.harvard.edu
 |
Abstract |
|---|
 Top Abstract MethodsResultsDiscussionReferences |
|---|
BACKGROUND: Previous studies have suggested that a history of diabetes and a prior MI confer similar risk for subsequent fatal coronary heart disease (CHD). Few studies have examined duration of diabetes in relation to mortality.
METHODS: We examined type 2 diabetes and prior MI in relation to mortality among 51,316 men aged 40 to 75 years in the Health Professionals Follow-up Study.
RESULTS: During 10 years of follow-up, we documented 4,150 deaths from all causes, including 1,124 deaths from CHD. Compared with men without diabetes or prior MI at baseline, the multivariate relative risks (RRs) for fatal CHD were 3.84 (95% confidence interval [CI], 3.12 to 4.71) for those with diabetes only, 7.88 (95% CI, 6.86 to 9.05) for those with MI only, and 13.41 (95% CI, 10.49 to 17.16) for those with both diabetes and MI. The corresponding RRs for total mortality were 1.91 (95% CI, 1.70 to 2.15), 2.23 (95% CI, 2.03 to 2.45), and 3.13 (95% CI, 2.56 to 3.84), respectively. Duration of diabetes was an independent risk factor for total as well as CHD mortality; the multivariate RRs of CHD mortality for increasing duration of diabetes (
5 years, 6 to 10 years, 11 to 15 years, 16 to 25 years, 26+ years) were 1.63, 1.93, 2.35, 2.31, and 3.87, respectively (p for trend <0.001), compared with nondiabetic participants.
CONCLUSIONS: These findings support that both diabetes and MI are associated with elevated total and CHD mortality, and having both conditions is particularly hazardous. Longer duration of diabetes is a strong predictor of death among diabetic men.
| ||||||||||||
Recent data suggest that diabetes and prior CHD confer similar risk for fatal CHD (6,7). In the Physicians’ Health Study, a prior CHD appeared to be associated with a greater risk of CHD mortality than diabetes in men (8), but that study did not examine duration of diabetes. Therefore, we compared the impact of diabetes and prior myocardial infarction (MI) on total and CHD mortality in men in the Health Professionals Follow-up Study (HPFS). We also evaluated the association between duration of diabetes and mortality.
|
Methods |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
For the current analysis, we excluded men who reported a diagnosis of type 1 diabetes (n = 101) and those who reported having diabetes diagnosed before turning 30 (n = 57). A total of 51,316 men were included in the analysis.
The study was approved by the Human Research Committees at the Harvard School of Public Health.
Documentation of diabetes and MI
The 1986 baseline questionnaire inquired about a history of physician-diagnosed diabetes mellitus. Biennial questionnaires mailed between 1988 and 1996 were used to identify newly diagnosed cases of diabetes. To confirm self-reports of diagnosed diabetes, a supplementary questionnaire was mailed to men reporting the diagnosis. Men were considered to have confirmed type 2 diabetes if any of the following criteria were met: 1) one or more classical symptoms (excessive thirst, polyuria, unexplained weight loss, hunger, or pruritus) plus a fasting plasma glucose level of 
140 mg/dl (7.8 mmol/l) or a random plasma glucose level of 200 mg/dl (11.1 mmol/l); 2) at least two elevated plasma glucose concentrations on different occasions (a fasting level of 140 mg/dl or a random level of 200 mg/dl and/or a concentration of 200 mg/dl after 2 h of oral glucose tolerance testing) in the absence of symptoms; or 3) treatment with hypoglycemic medications (insulin or oral hypoglycemic agents). We used the National Diabetes Data Group criteria (10) because the analytic cohort preceded the publication of the American Diabetes Association guideline in 1997 (11).
The validity of self-reported type 2 diabetes was documented in a subsample of 71 men from the HPFS. A physician blinded to the information reported on the supplementary questionnaire reviewed the medical records according to the diagnostic criteria. Of the 71 patients, 12 had incomplete records, for example, absent laboratory data (n = 2) or incomplete laboratory data (n = 9). Among the remaining 59 cases, the diagnosis of type 2 diabetes was confirmed in 57 (97%). One patient denied the diagnosis, and another lacked evidence of diabetes in his submitted records. In the primary analyses, we used self-reported diabetes status. In a secondary analysis, we used only the confirmed diabetic cases.
Diagnosis of MI was also reported through questionnaires. We used self-reported information in the analysis. Validation studies among female nurses (12) and male physicians (13) have shown reliable reporting of CHD events compared with medical record reviews.
Ascertainment of death
Deaths were documented by responses to follow-up questionnaires by family members or the postal service and by a search of the National Death Index. Participants who did not respond were assumed to be alive if they were not listed in the National Death Index. If a death from cancer or cardiovascular disease (CVD) was identified, we sought medical records to confirm the cause of death. We obtained death certificates for deaths whose cause was not confirmed by other sources. Cause of death was decided on the basis of all available information, including death certificates, medical records, and autopsy results. We classified deaths as being due to CHD (International Classification of Diseases, Ninth Revision, codes 410-414), CVD (codes 390-459, 795), or all other causes.
Statistical analysis
We calculated mortality according to the history of diabetes and CHD at baseline as well as the diagnoses updated every questionnaire cycle during follow-up. Participants contributed person-time from the date of return of the 1986 questionnaire until the date of death or January 31, 1996, whichever came first. The relative risk of death was calculated as the rate for a given category of diabetes and CHD status as compared with the rate for the referent category of no diabetes and no CHD. Duration of clinical diabetes was calculated as years since first diagnosis of diabetes. The variable was updated every questionnaire cycle and was divided into five categories (5 years, 6 to 10 years, 11 to 15 years, 16 to 25 years, 26+ years). For the analysis of duration of diabetes, we used nondiabetic participants as the reference. We employed Cox proportional hazards regression (14) in analyses. To control as finely as possible for confounding by age, calendar time, and any possible two-way interactions between these two time scales, we stratified the analysis jointly by age in months at start of follow-up and calendar year of the current questionnaire cycle. The time scale for the analysis was then measured as months since the start of the current questionnaire cycle, which was equivalent to age in months because of the way we structured the data and formulated the model for analysis. Multivariate models adjusted for smoking status, body mass index, physical activity, parental history of MI before age 60 years, alcohol intake, and vitamin E supplement use, simultaneously. The SAS PHREG procedure (SAS Institute, Cary North Carolina) was used for all analysis, and the Anderson-Gill data structure (15) was used to handle time-varying covariates efficiently, where a new data record was created for every questionnaire cycle at which a participant was at risk, with covariates set to their values at the time that the questionnaire was returned. All covariates except parental history of MI were updated in each questionnaire cycle. For all relative risks, 95% confidence intervals (CIs) were calculated. Tests for trend were conducted using the median value for each category of duration of diabetes as a continuous variable. All p values were two-sided.
|
Results |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
|
|
|
5 years had a relative risk of 1.48 (95% CI, 1.27 to 1.72), and those with diagnosis more than 26 years had a relative risk of 1.91 (95% CI, 1.43 to 2.55). A stronger association was found for death from CHD; the relative risk for those with diabetes diagnosis more than 26 years was 3.87 (95% CI, 2.64 to 5.67) compared with nondiabetic men. Adjusting for history of high blood cholesterol and hypertension did not materially alter the overall associations.
|
|
70 years. The increased CHD mortality associated with having both diabetes and MI was more striking; the relative risks were 33.66 (95% CI, 17.26 to 65.65) for men <60 years and 9.50 (95% CI, 7.19 to 12.56) for those 70 years.
|
|
Discussion |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
Our findings support current guidelines that recommend aggressive management of cardiovascular risk factors including hypertension, dyslipidemia, and lifestyle factors (smoking, obesity, and diet) in diabetic patients. Recent guidelines from the American Diabetes Association (16) and National Cholesterol Education Program (17) also recommend the same cholesterol-lowering goal for people with diabetes and no clinical CHD as for those with pre-existing CHD.
Review of other epidemiologic studies
Several recent studies have compared the impact of diabetes and prior CHD on total and CHD mortality. A Finnish study, which combined both men and women, reported that CHD mortality among subjects with diabetes but no CHD was not significantly different from those with CHD but no diabetes (6). In the Nurses’ Health Study of women, the impacts of diabetes and prior CHD were similar for total and CHD mortality (7). Our results in men were in accord with the Physicians Health Study which found that the magnitude of excess risk conferred by diabetes was similar to that conferred by prior CHD for all-cause mortality but weaker for CHD mortality in men (8).
Few studies have evaluated duration of diabetes in relation to CHD mortality. The Whitehall Study with 15 years of follow-up of men did not find any increase of mortality with increasing duration of diabetes (18). However, there were only 47 deaths among diabetic patients with known duration of diabetes. The London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics also did not find any association between duration of type 2 diabetes and CVD mortality among 246 diabetic patients (19). Lack of statistical power might be an explanation for these null findings. The Nurses’ Health Study found a linear association between duration of diabetes and total as well as CHD mortality in women (7). Our results in men also indicated increased total and CHD mortality with increasing duration of diabetes.
Strengths and limitations
Our study provided a unique opportunity to evaluate diabetes and CHD in relation to mortality using baseline as well as updated disease status with a large sample size and relatively long duration of follow-up. The follow-up rate in this cohort was high. We had detailed information on various cardiovascular risk factors and adjusted for them in multivariate analyses.
Several limitations need to be considered. First, diagnosis of diabetes and CHD were self-reported. Although studies have indicated that self-reporting of these medical conditions are reliable, some misclassification is inevitable. Second, our nondiabetic participants were not uniformly screened for glucose intolerance and may include a few subclinical cases of diabetes. However, we believe that the proportion of undiagnosed diabetes in our cohort of health professionals is small relative to the general population due to their education and access to health care. Third, the reported duration of diabetes might be underestimated because the actual onset of diabetes frequently precedes clinical diagnosis by several years. However, these possibilities would have attenuated the association between diabetes and mortality and led to underestimates of the risk in the diabetic population. Fourth, the reference group of participants without diabetes or CHD will include those with impaired glucose tolerance, a precursor of diabetes, which also increases total as well as CVD mortality (20). If these people with impaired glucose tolerance were excluded from the reference, the excess risk related to either diabetes or CHD would have been even greater. Finally, because the vast majority of our participants were white, our findings may not be generalized to other racial groups.
In our analysis we used the National Diabetes Data Group criteria (10) because all of the diabetic patients were diagnosed before 1996, before the release of new criteria from the American Diabetes Association (11). Thus, the participants without diabetes will include some diabetic cases based on current criteria. However, again, assigning the cases to diabetic groups would likely make the results stronger.
Conclusions
In this population of men, both a prior MI and diabetes elevated risk of total and CHD mortality substantially. A combination of diabetes and MI is associated with dramatically increased risk of total and CHD mortality. Increasing duration of diabetes is associated with increased risk of total and CHD mortality.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  A. C. Dale, L. J Vatten, T. I. Nilsen, K. Midthjell, and R. Wiseth Secular decline in mortality from coronary heart disease in adults with diabetes mellitus: cohort study BMJ, August 13, 2008; 337(jul01_2): a236 - a236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Dale, T. I. Nilsen, L. Vatten, K. Midthjell, and R. Wiseth Diabetes mellitus and risk of fatal ischaemic heart disease by gender: 18 years follow-up of 74 914 individuals in the HUNT 1 Study Eur. Heart J., December 1, 2007; 28(23): 2924 - 2929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Simon, H. Chen, M. Schwarzschild, and A. Ascherio Hypertension, hypercholesterolemia, diabetes, and risk of Parkinson disease Neurology, October 23, 2007; 69(17): 1688 - 1695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Siyambalapitiya, U. Bulugahapitiya, J. Sithole, S. Song, D. J.S. Fernando, and I. Idris Combining Population Health and Baseline Risk Strategy by Determining an Age Cutoff for Initiating Statins in Patients With Diabetes: A population-based study Diabetes Care, August 1, 2007; 30(8): 2025 - 2029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Hsueh, E. D. Abel, J. L. Breslow, N. Maeda, R. C. Davis, E. A. Fisher, H. Dansky, D. A. McClain, R. McIndoe, M. K. Wassef, et al. Recipes for Creating Animal Models of Diabetic Cardiovascular Disease Circ. Res., May 25, 2007; 100(10): 1415 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. W. Gowdak, F. J. de Paula, L. A. M. Cesar, E. E. M. Filho, L. E. Ianhez, E. M. Krieger, J. A. F. Ramires, and J. J. G. De Lima Diabetes and coronary artery disease impose similar cardiovascular morbidity and mortality on renal transplant candidates Nephrol. Dial. Transplant., May 1, 2007; 22(5): 1456 - 1461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Erdmann, J. A. Dormandy, B. Charbonnel, M. Massi-Benedetti, I. K. Moules, A. M. Skene, and on behalf of the PROactive Investigators The Effect of Pioglitazone on Recurrent Myocardial Infarction in 2,445 Patients With Type 2 Diabetes and Previous Myocardial Infarction: Results From the PROactive (PROactive 05) Study J. Am. Coll. Cardiol., May 1, 2007; 49(17): 1772 - 1780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yang, N. Sambandam, X. Han, R. W. Gross, M. Courtois, A. Kovacs, M. Febbraio, B. N. Finck, and D. P. Kelly CD36 Deficiency Rescues Lipotoxic Cardiomyopathy Circ. Res., April 27, 2007; 100(8): 1208 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. V. G. Katakam, J. E. Jordan, J. A. Snipes, C. D. Tulbert, A. W. Miller, and D. W. Busija Myocardial preconditioning against ischemia-reperfusion injury is abolished in Zucker obese rats with insulin resistance Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R920 - R926. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Buse, H. N. Ginsberg, G. L. Bakris, N. G. Clark, F. Costa, R. Eckel, V. Fonseca, H. C. Gerstein, S. Grundy, R. W. Nesto, et al. Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus: A Scientific Statement From the American Heart Association and the American Diabetes Association Circulation, January 2, 2007; 115(1): 114 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Buse, H. N. Ginsberg, G. L. Bakris, N. G. Clark, F. Costa, R. Eckel, V. Fonseca, H. C. Gerstein, S. Grundy, R. W. Nesto, et al. Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus: A scientific statement from the American Heart Association and the American Diabetes Association Diabetes Care, January 1, 2007; 30(1): 162 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Bax, R. O. Bonow, D. Tschope, S. E. Inzucchi, E. Barrett, and on behalf of the Global Dialogue Group for the Eva The Potential of Myocardial Perfusion Scintigraphy for Risk Stratification of Asymptomatic Patients With Type 2 Diabetes J. Am. Coll. Cardiol., August 15, 2006; 48(4): 754 - 760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Joyeux-Faure, E. Rossini, C. Ribuot, and P. Faure Fructose-fed rat hearts are protected against ischemia-reperfusion injury. Experimental Biology and Medicine, April 1, 2006; 231(4): 456 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Grundy Diabetes and Coronary Risk Equivalency: What does it mean? Diabetes Care, February 1, 2006; 29(2): 457 - 460. [Full Text] [PDF]
|
|
|
|
|
|
A. Juutilainen, S. Lehto, T. Ronnemaa, K. Pyorala, and M. Laakso Type 2 Diabetes as a "Coronary Heart Disease Equivalent": An 18-year prospective population-based study in Finnish subjects Diabetes Care, December 1, 2005; 28(12): 2901 - 2907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Valensi, J. Paries, V. Brulport-Cerisier, F. Torremocha, R.-N. Sachs, G. Vanzetto, E. Cosson, B. Lormeau, J.-R. Attali, R. Marechaud, et al. Predictive Value of Silent Myocardial Ischemia for Cardiac Events in Diabetic Patients: Influence of age in a French multicenter study Diabetes Care, November 1, 2005; 28(11): 2722 - 2727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Elhendy, A. Huurman, A. F.L. Schinkel, J. J. Bax, R. T. van Domburg, R. Valkema, E. Biagini, and D. Poldermans Association of Ischemia on Stress99mTc-Tetrofosmin Myocardial Perfusion Imaging with All-Cause Mortality in Patients with Diabetes Mellitus J. Nucl. Med., October 1, 2005; 46(10): 1589 - 1595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Mantzoros, T. Li, J. E. Manson, J. B. Meigs, and F. B. Hu Circulating Adiponectin Levels Are Associated with Better Glycemic Control, More Favorable Lipid Profile, and Reduced Inflammation in Women with Type 2 Diabetes J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4542 - 4548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cusick, A. D. Meleth, E. Agron, M. R. Fisher, G. F. Reed, G. L. Knatterud, F. B. Barton, M. D. Davis, F. L. Ferris III, E. Y. Chew, et al. Associations of Mortality and Diabetes Complications in Patients With Type 1 and Type 2 Diabetes: Early Treatment Diabetic Retinopathy Study report no. 27 Diabetes Care, March 1, 2005; 28(3): 617 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Boccara and A Cohen Interplay of diabetes and coronary heart disease on cardiovascular mortality Heart, December 1, 2004; 90(12): 1371 - 1373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S G Wannamethee, A G Shaper, and L Lennon Cardiovascular disease incidence and mortality in older men with diabetes and in men with coronary heart disease Heart, December 1, 2004; 90(12): 1398 - 1403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Lim, R. J. MacFadyen, and G. Y. H. Lip Diabetes Mellitus, the Renin-Angiotensin-Aldosterone System, and the Heart Arch Intern Med, September 13, 2004; 164(16): 1737 - 1748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Malik, N. D. Wong, S. S. Franklin, T. V. Kamath, G. J. L'Italien, J. R. Pio, and G. R. Williams Impact of the Metabolic Syndrome on Mortality From Coronary Heart Disease, Cardiovascular Disease, and All Causes in United States Adults Circulation, September 7, 2004; 110(10): 1245 - 1250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Schulze, E. B. Rimm, I. Shai, N. Rifai, and F. B. Hu Relationship Between Adiponectin and Glycemic Control, Blood Lipids, and Inflammatory Markers in Men With Type 2 Diabetes Diabetes Care, July 1, 2004; 27(7): 1680 - 1687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Schulze, E. B. Rimm, T. Li, N. Rifai, M. J. Stampfer, and F. B. Hu C-Reactive Protein and Incident Cardiovascular Events Among Men With Diabetes Diabetes Care, April 1, 2004; 27(4): 889 - 894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Winer and J. R. Sowers Epidemiology of Diabetes J. Clin. Pharmacol., April 1, 2004; 44(4): 397 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Fox, L. Sullivan, R. B. D'Agostino Sr, and P. W.F. Wilson The Significant Effect of Diabetes Duration on Coronary Heart Disease Mortality: The Framingham Heart Study Diabetes Care, March 1, 2004; 27(3): 704 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Lee, A. R. Folsom, J. S. Pankow, F. L. Brancati, and For the Atherosclerosis Risk in Communities (ARIC) Cardiovascular Events in Diabetic and Nondiabetic Adults With or Without History of Myocardial Infarction Circulation, February 24, 2004; 109(7): 855 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Jordan, S. A. Simandle, C. D. Tulbert, D. W. Busija, and A. W. Miller Fructose-Fed Rats Are Protected against Ischemia/Reperfusion Injury J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 1007 - 1011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ma, J. Cutter, C. E. Tan, S. K. Chew, and E. S. Tai Associations of Diabetes Mellitus and Ethnicity with Mortality in a Multiethnic Asian Population: Data from the 1992 Singapore National Health Survey Am. J. Epidemiol., September 15, 2003; 158(6): 543 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Hu, D. Zhang, L. Swenson, G. Chakrabarti, E. D. Abel, and S. E. Litwin Minimally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1261 - H1269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-H. Mak and S. M Haffner Diabetes abolishes the gender gap in coronary heart disease Eur. Heart J., August 1, 2003; 24(15): 1385 - 1386. [Full Text] [PDF]
|
|
|
|
|
|
F. B. Hu and J. E. Manson Walking: The Best Medicine for Diabetes? Arch Intern Med, June 23, 2003; 163(12): 1397 - 1398. [Full Text] [PDF]
|
|
| |||||||||||||
