Skip to main content
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • Log out
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes Care

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • Log out
  • My Cart

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Epidemiology/Health Services/Psychosocial Research

The Significant Effect of Diabetes Duration on Coronary Heart Disease Mortality

The Framingham Heart Study

  1. Caroline S. Fox, MD, MPH12,
  2. Lisa Sullivan, PHD13,
  3. Ralph B. D’Agostino, Sr, PHD13 and
  4. Peter W.F. Wilson, MD14
  1. 1National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts
  2. 2National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
  3. 3Department of Mathematics and Statistics, Boston University, Boston, Massachusetts
  4. 4School of Medicine, Boston University, Boston, Massachusetts
  1. Address correspondence and reprint requests to Caroline S. Fox, MD, MPH, Framingham Heart Study, 73 Mt. Wayte Ave., Suite 2, Framingham, MA 01702. E-mail: caroline{at}fram.nhlbi.nih.gov
Diabetes Care 2004 Mar; 27(3): 704-708. https://doi.org/10.2337/diacare.27.3.704
PreviousNext
  • Article
  • Figures & Tables
  • Info & Metrics
  • PDF
Loading

The Framingham Heart Study

Abstract

OBJECTIVE—The risk of coronary heart disease (CHD) in type 2 diabetes is two- to threefold higher than in the general population, but the effect of diabetes duration on CHD risk has not been well characterized. We hypothesized that duration of diabetes is an important predictor of incident CHD among people with diabetes.

RESEARCH DESIGN AND METHODS—The duration of diabetes (fasting glucose ≥126 mg/dl, random glucose ≥200 mg/dl, or use of an oral hypoglycemic agent or insulin) was assessed in participants with diabetes in the original and offspring cohorts of the Framingham Heart Study. Only subjects with diabetes diagnosed between the ages of 30 and 74 years, without a history of ketoacidosis, and free of cardiovascular disease at the baseline evaluation were included. Cox proportional hazards models were used to estimate the hazard ratio of incident CHD events and mortality over a 12-year follow-up period; models were adjusted for known CHD risk factors.

RESULTS—Among 588 person-exams with diabetes (mean age 58 ± 9 years, 56% men), there were 86 CHD events, including 36 deaths. After adjustment for age, sex, and CHD risk factors, the risk of CHD was 1.38 times higher for each 10-year increase in duration of diabetes (95% CI 0.99–1.92), and the risk for CHD death was 1.86 times higher (1.17–2.93) for the same increase in duration of diabetes.

CONCLUSIONS—Duration of diabetes increases the risk of CHD death independent of coexisting risk factors. Further research is necessary to understand the pathophysiology of this increased risk.

  • CABG, coronary artery bypass graft
  • CHD, coronary heart disease
  • CVD, cardiovascular disease

Type 2 diabetes confers a two- to threefold increase in the risk of cardiovascular disease (CVD) (1). Nearly 11 million Americans with diabetes will develop CVD (2,3), and two-thirds will die from coronary heart disease (CHD) (2).

It has been suggested that the duration of diabetes may be a CVD risk factor. The results of previous studies that have examined this association have been inconclusive. Some reports have noted an association between type 2 diabetes disease duration and the development of CVD (4–9), whereas others have not (10,11).

Many prior studies were unable to reliably identify the onset of diabetes due to lack of antecedent measures of glycemia. The Framingham Heart Study has measured blood glucose every 2–4 years, enabling an accurate inception of diabetes. Thus, we sought to assess the effect of diabetes duration on incident CHD morbidity and mortality, hypothesizing that there would be an association between diabetes duration and the development of CHD.

RESEARCH DESIGN AND METHODS

The subjects from this study were drawn from the original and offspring cohorts of the Framingham Heart Study. Beginning in 1948, 5,209 men and women aged 28–62 years were enrolled in the original cohort study. Starting in 1971, offspring and spouses of offspring or the original cohort were enrolled in the study. The selection criteria and study design have been described elsewhere (12,13). The standard clinic examination included an interview, a physical examination, and laboratory tests. Cardiovascular events, including all major hospitalizations and deaths, were documented throughout follow-up. Original cohort subjects were invited to attend examinations every 2 years, and offspring subjects were invited to attend examinations every 4 years.

We selected three original cohort examinations, ∼12 years apart (1954–1958, 1968–1972, and 1981–1984), and two offspring examinations, 12 years apart (1979–1983 and 1991–1995), from which to draw participants; the study design is schematically represented in Fig. 1. Examination dates were chosen to be nonoverlapping with respect to follow-up. Participants could contribute diabetes duration information at more than one examination provided that they reached the next examination free of a CVD event. For example, a 60-year-old diabetic subject with 5 years of diabetes duration attending an examination in 1956 could contribute information over the next 12 years for this diabetes duration. If this subject was free of CVD in 1968, the subject could provide additional diabetes duration as a 72-year-old with 17 years of diabetes duration. The majority of subjects contributed only one person-exam (n = 379), 103 individuals contributed two person-exams, and only 1 subject contributed three person-exams. Altogether there are 483 individuals in the analytic sample and 588 person-exams. Follow-up information was available on 100% of the 588 person-exams.

Diabetes diagnosis and diabetes duration

Diabetes was diagnosed by either a fasting plasma glucose ≥126 mg/dl, a nonfasting plasma glucose ≥200 mg/dl, or treatment with either insulin or an oral hypoglycemic agent. Subjects with a history of ketoacidosis or age at onset <30 years old were excluded; subjects with an age at onset >74 years old were also excluded. Diabetes duration, the exposure variable in this study, was determined by identifying the date of onset of diabetes as the midpoint of the interval during which the subject was free of diabetes and then developed diabetes. Charts were reviewed to determine the date of diagnosis of subjects who entered the study with diabetes or who did not return for a follow-up examination within an 8-year period. The duration of diabetes was determined at each of the five examinations. All subjects with preexisting CVD were excluded.

Ascertainment of CVD outcomes

A panel of three physicians reviewed each cardiovascular event according to preestablished criteria. CHD included myocardial infarction and sudden and nonsudden CHD death; this outcome is often referred to as “hard” CHD. CHD death included deaths attributable to myocardial infarction and sudden and nonsudden CHD deaths. CVD included CHD, as well as angina, coronary insufficiency (unstable angina with ischemic electrocardiogram changes), congestive heart failure, and atheroembolic brain infarction; CVD death included deaths attributable to these causes.

Details regarding the methods of risk factor measurement and laboratory analysis have been described elsewhere (14). Each examination included CVD assessment, 12-lead electrocardiogram, and blood testing. Measured covariates were assessed at each of the five examinations. Subjects with a systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg (average of two readings taken by the examining physician), or on antihypertensive medication were defined as hypertensive. Lipid measures included total cholesterol. Smoking status was defined as number of cigarettes smoked per day in the year preceding the exam. BMI was defined as weight (in kilograms) divided by the square of height (in meters). Covariate assessment was made at the time of the examination.

Statistical analysis

Cox proportional hazards survival models were developed to examine the risk of increasing diabetes duration on development of CHD, CHD death, CVD, CVD death, total mortality, and non-CVD mortality, each considered separately. Descriptive statistics were generated on all study variables, including means and SDs for continuous measures and percentages for discrete measures. Statistics were generated for the total sample and then by 5-year increments in duration of diabetes. Diabetic subjects from the selected baseline examinations were pooled, and diabetes duration entered the model as a continuous variable. Subjects were followed for 12 years to ascertain outcome status. In the Cox models, the outcome time axis utilized was time to event, including CVD, CVD death, CHD, CHD death, total mortality, or non-CVD mortality, depending on the specific outcome used in the Cox models. In the Cox models, the exposure variable used was diabetes duration as a continuous variable. Crude, age- and sex-adjusted, and multivariable (age, sex, systolic blood pressure, hypertension treatment, total cholesterol, BMI, smoking status, and electrocardiogram left ventricular hypertrophy) models were estimated. Hazard ratios (HRs) are presented as the risk of CVD or all-cause mortality per 10-year increase in the duration of diabetes. To examine whether the effect of duration of diabetes on morbidity and mortality was linear, we estimated Cox models with linear and quadratic terms for duration of diabetes. The quadratic terms failed to reach statistical significance, suggesting that the risk of diabetes duration has a linear effect on morbidity and mortality.

RESULTS

There were 588 person-exams (329 men and 259 women) with diabetes, with a mean age of 58 years. Mean duration of diabetes was 7.8 years, ranging from 0.3–44.5 years; five person-exams had a duration of >25 years. When baseline characteristics were examined by 5-year increments of duration, those with longer duration were older, more likely to be hypertensive, and less likely to smoke (Table 1). Morbidity and mortality rates per 1,000 person-years by 5-year category of diabetes duration are presented in Table 2.

There were 193 CVD events, including 55 deaths. In crude models, the risk of CVD was 1.23 times higher for each 10-year increase in duration of diabetes (95% CI 0.98–1.54; P = 0.07). These results were not different in age- and sex-adjusted and multivariable-adjusted models (Table 3). In fully adjusted models, the risk of diabetes duration on CVD death was not significant (odds ratio [OR] 1.44, 95% CI 0.97–2.15; P = 0.07). Overall, there were 86 CHD events, including 36 deaths. In crude models, the risk of CHD was 1.33 times higher for each 10-year increase in diabetes duration (0.96–1.84; P = 0.08). These results persisted in age-, sex-, and multivariable-adjusted models (Table 3).

There were 36 CHD deaths. In crude models, the risk of CHD was 1.83 times higher for each 10-year increase in diabetes duration (95% CI 1.18–2.83; P < 0.007). These results persisted in age- and sex-adjusted models and multivariable-adjusted models (HR 1.86, 95% CI 1.17–2.93; P < 0.008) (Table 3). Overall, there were 125 deaths. For each 10-year increase in diabetes duration, there was no increase in the risk of all-cause mortality (1.21, 0.91–1.60; P = 0.19) (Table 3).

There were 70 non-CVD deaths. The multivariable-adjusted HR per decade of diabetes was 0.87 (95% CI 0.58–1.31; P = 0.50) (Table 3).

CONCLUSIONS

Among people with type 2 diabetes, duration of diabetes is significantly and positively related to the risk of CHD mortality. For each decade of duration of diabetes, the 10-year risk of CHD death was 86% greater. Duration of diabetes was not related to CHD morbidity or CVD morbidity or mortality, suggesting a mechanism of action that is specific to CHD death.

The association between duration of type 2 diabetes and the development of CVD is controversial. Some studies have noted an association (4–9), whereas others have not (10,11). In the reports with a significant association, many have used CHD death as an end point (4,5,7,8), suggesting that a unique mechanism may exist between type 2 diabetes and coronary death.

Indeed, an autopsy study demonstrated an association between diabetes duration and the extent of atherosclerosis and myocardial lesions (15). Clinically, patients with diabetes have been shown to have less development of coronary collateral vessels (16). Together, these observations may explain why mortality following a myocardial infarction in patients with diabetes is higher than in patients without diabetes (17).

Further insights regarding the association between diabetes and cardiovascular death may be explained by the Bypass Angioplasty Revascularization Investigation trial. Among participants with diabetes, the trial demonstrated a survival benefit for coronary artery bypass graft (CABG) surgery as compared with percutaneous transluminal coronary angioplasty (18). To elucidate the mechanism for this differential survival benefit, mortality rates from subsequent Q-wave myocardial infarctions were compared. Patients with diabetes who underwent CABG had a lower Q-wave myocardial infarction mortality rate in comparison with diabetic participants who had not undergone CABG (19). Detre et al. hypothesized that this difference may be due to greater vessel patency in patients with diabetes following CABG compared with percutaneous transluminal coronary angioplasty. Indeed, those who underwent CABG had nearly half as many remaining significant lesions (19). It is possible that the positive relation between diabetes duration and CHD death in our study was mediated in a similar way. A greater number of atherosclerotic lesions may exist in those with longer duration of diabetes, thereby increasing the risk of CHD death in the setting of a coronary event. This mechanism may also explain why duration of diabetes was associated with an increased risk for CHD death, but not nonfatal events.

In addition to a possible direct effect of diabetes duration on atherosclerotic lesion formation, several additional mechanisms may be uniquely related to the development of CVD in the setting of longer diabetes duration. Diabetes duration has been shown to increase the risk of microalbuminuria (20,21), and the risk of CHD in the setting of nephropathy has been shown to be markedly influenced by diabetes duration (22). Microalbuminuria is a potent risk factor for CVD among patients with diabetes (23), suggesting an additional mechanism of action to explain the impact of diabetes duration on CHD death.

Vascular reactivity, a marker of impaired endothelial dysfunction, has been shown to be diminished in long-term type 1 diabetes (24), and impaired vascular reactivity may coexist among subjects with early onset coronary artery disease (25). Thus, one may speculate that longer exposure to hyperglycemia may increase the risk of endothelial dysfunction, increasing the risk of CVD.

Other potential mechanisms may exist as well. Heart rate variability has been shown to be reduced among those with diabetes (26). Reduced heart rate variability increases the risk of cardiovascular events (27) and sudden cardiac death among subjects with known heart failure (28). It is possible that a longer duration of diabetes might be associated with autonomic neuropathy and reduced heart rate variability, increasing the risk of cardiovascular death. Additionally, abnormalities in clotting mechanisms have been shown to be associated with diabetes (29,30), suggesting the possibility for an increased risk of acute thrombosis. Lastly, diabetes has been shown to be associated with systemic oxidative stress (31), and long-term exposure to increased amounts of oxidative stress may explain another mechanism for the increased risk of CHD death among diabetic patients.

This analysis is complicated by the observation that longer duration of diabetes is also associated with older age. If our findings were primarily due to confounding by age, we would expect to see similar results in both cardiac and noncardiac causes of death. However, duration of diabetes does not appear to be related to noncardiac death, suggesting that the association between increasing age and duration does not explain our observed association between duration and CHD death.

This study has strengths over prior studies that have examined the relation between diabetes duration and CVD risk. Serial screening of serum glucose enabled the early detection of diabetes. In fact, diabetes is often present 4–7 years before its eventual diagnosis (32). Additionally, we excluded subjects who presented with signs and symptoms that suggested type 1 diabetes. In our analyses, covariate assessment was made contemporaneously with the diagnosis of diabetes. Lastly, all CHD outcomes were adjudicated by a three-member physician panel.

Certain limitations of our study deserve mention. The Framingham Heart Study is neither ethnically nor geographically representative of the U.S. However, the relations of risk factors to CHD outcomes observed in the Framingham Heart Study have recently been validated in six ethnically and geographically diverse cohorts and were found to be applicable in other populations (33). We were also limited in our definition of diabetes, as members of the original cohort of the Framingham Heart Study did not have fasting measures of glucose. Instead, we had to rely on nonfasting glucose ≥200 mg/dl to diagnose diabetes. Indeed, this operational definition of diabetes may be less sensitive for the diagnosis of diabetes and is likely to identify those with more severe diabetes. Lastly, failure to reach statistical significance in some of our analyses may be due to small sample size. Assuming the event rates we observed here, in order to detect HRs on the order of 1.25 (approximately the effects we observed for CVD, CHD, and total mortality) we would need at least 1,060, 2,400, and 1,600 subjects per comparison group, respectively, to ensure 80% power in two-sided analysis with a 5% level of significance.

In conclusion, duration of diabetes increases the risk of CHD death independent of coexisting risk factors. Further research is necessary to understand the pathophysiology of this increased risk.

Figure 1—
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1—

Schematic representation of study design.

View this table:
  • View inline
  • View popup
Table 1—

Baseline characteristics of study participants by duration of diabetes

View this table:
  • View inline
  • View popup
Table 2—

Age- and sex-adjusted 10-year morbidity and mortality rates per 1,000 person-years by 5-year category of diabetes duration

View this table:
  • View inline
  • View popup
Table 3—

Risk of events for each 10-year increase in duration of diabetes

Acknowledgments

This work was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study (N01-HC-25195).

Footnotes

  • DIABETES CARE

References

  1. ↵
    Kannel WB, McGee DL: Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study. Diabetes Care 2:120–126, 1979
    OpenUrlAbstract/FREE Full Text
  2. ↵
    American Heart Association: 2003 Heart and Stroke Statistical Update. Dallas, TX, American Heart Association, 2002
  3. ↵
    Wilson PWF, D’Agostino RB, Parise H, Kannel WB: Does obesity influence the lifetime risk of CVD in type 2 diabetes? (Abstract). Circulation 104:II-804, 2003
    OpenUrl
  4. ↵
    Cho E, Rimm EB, Stampfer MJ, Willett WC, Hu FB: The impact of diabetes mellitus and prior myocardial infarction on mortality from all causes and from coronary heart disease in men. J Am Coll Cardiol 40:954–960, 2002
    OpenUrlCrossRefPubMedWeb of Science
  5. ↵
    Hu FB, Stampfer MJ, Solomon CG, Liu S, Willett WC, Speizer FE, Nathan DM, Manson JE: The impact of diabetes mellitus on mortality from all causes and coronary heart disease in women: 20 years of follow-up. Arch Intern Med 161:1717–1723, 2001
    OpenUrlCrossRefPubMedWeb of Science
  6. Morgan CL, Currie CJ, Stott NC, Smithers M, Butler CC, Peters JR: The prevalence of multiple diabetes-related complications. Diabet Med 17:146–151, 2000
    OpenUrlCrossRefPubMedWeb of Science
  7. ↵
    Brun E, Nelson RG, Bennett PH, Imperatore G, Zoppini G, Verlato G, Muggeo M: Diabetes duration and cause-specific mortality in the Verona Diabetes Study. Diabetes Care 23:1119–1123, 2000
    OpenUrlAbstract/FREE Full Text
  8. ↵
    Sievers ML, Nelson RG, Knowler WC, Bennett PH: Impact of NIDDM on mortality and causes of death in Pima Indians. Diabetes Care 15:1541–1549, 1992
    OpenUrlAbstract/FREE Full Text
  9. ↵
    Nelson RG, Sievers ML, Knowler WC, Swinburn BA, Pettitt DJ, Saad MF, Liebow IM, Howard BV, Bennett PH: Low incidence of fatal coronary heart disease in Pima Indians despite high prevalence of non-insulin-dependent diabetes. Circulation 81:987–995, 1990
    OpenUrlAbstract/FREE Full Text
  10. ↵
    Jarrett RJ, Shipley MJ: Type 2 (non-insulin-dependent) diabetes mellitus and cardiovascular disease: putative association via common antecedents; further evidence from the Whitehall Study. Diabetologia 31:737–740, 1988
    OpenUrlCrossRefPubMedWeb of Science
  11. ↵
    Haffner SM, Mitchell BD, Stern MP, Hazuda HP: Macrovascular complications in Mexican Americans with type II diabetes. Diabetes Care 14:665–671, 1991
    OpenUrlAbstract/FREE Full Text
  12. ↵
    Dawber TR, Kannel WB, Lyell LP: An approach to longitudinal studies in a community: the Framingham Heart Study. Ann N Y Acad Sci 107:539–556, 1963
  13. ↵
    Feinleib M, Kannel WB, Garrison RJ, McNamara PM, Castelli WP: The Framingham Offspring Study: design and preliminary data. Prev Med 4:518–525, 1975
    OpenUrlCrossRefPubMedWeb of Science
  14. ↵
    Cupples LA, D’Agostino RB: Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Study, 30-year follow-up. In The Framingham Heart Study: An Epidemiological Investigation of Cardiovascular Disease. Kannel WB, Polf PA, Garrison RJ, Eds. Washington, DC, U.S. Govt. Printing Office, 1987 (NIH publ. no. 87-203, section 34)
  15. ↵
    Burchfiel CM, Reed DM, Marcus EB, Strong JP, Hayashi T: Association of diabetes mellitus with coronary atherosclerosis and myocardial lesions: an autopsy study from the Honolulu Heart Program. Am J Epidemiol 137:1328–1340, 1993
    OpenUrlAbstract/FREE Full Text
  16. ↵
    Abaci A, Oguzhan A, Kahraman S, Eryol NK, Unal S, Arinc H, Ergin A: Effect of diabetes mellitus on formation of coronary collateral vessels. Circulation 99:2239–2242, 1999
    OpenUrlAbstract/FREE Full Text
  17. ↵
    Jacoby RM, Nesto RW: Acute myocardial infarction in the diabetic patient: pathophysiology, clinical course and prognosis. J Am Coll Cardiol 20:736–744, 1992
    OpenUrlCrossRefPubMedWeb of Science
  18. ↵
    Bypass Angioplasty Revascularization Investigation (BARI) Investigators: Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med 335:217–225, 1996
    OpenUrlCrossRefPubMedWeb of Science
  19. ↵
    Detre KM, Lombardero MS, Brooks MM, Hardison RM, Holubkov R, Sopko G, Frye RL, Chaitman BR, Bypass Angioplasty Revascularization Investigation Investigators: The effect of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction. N Engl J Med 342:989–997, 2000
    OpenUrlCrossRefPubMedWeb of Science
  20. ↵
    Gerstein HC, Mann JF, Pogue J, Dinneen SF, Hallé J-P, Hoogwerf B, Joyce C, Rashkow A, Young J, Zinman B, Yusuf S, HOPE Study Investigators: Prevalence and determinants of microalbuminuria in high-risk diabetic and nondiabetic patients in the Heart Outcomes Prevention Evaluation study. Diabetes Care 23 (Suppl. 2):B35–B39, 2000
  21. ↵
    Orchard TJ, Dorman JS, Maser RE, Becker DJ, Drash AL, Ellis D, LaPorte RE, Kuller LH: Prevalence of complications in IDDM by sex and duration: Pittsburgh Epidemiology of Diabetes Complications Study II. Diabetes 39:1116–1124, 1990
    OpenUrlAbstract/FREE Full Text
  22. ↵
    Tuomilehto J, Borch-Johnsen K, Molarius A, Forsen T, Rastenyte D, Sarti C, Reunanen A: Incidence of cardiovascular disease in type 1 (insulin-dependent) diabetic subjects with and without diabetic nephropathy in Finland. Diabetologia 41:784–790, 1998
    OpenUrlCrossRefPubMedWeb of Science
  23. ↵
    Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Halle JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S, HOPE Study Investigators: Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 286:421–426, 2001
    OpenUrlCrossRefPubMedWeb of Science
  24. ↵
    Clarkson P, Celermajer DS, Donald AE, Sampson M, Sorensen KE, Adams M, Yue DK, Betteridge DJ, Deanfield JE: Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels. J Am Coll Cardiol 28:573–579, 1996
    OpenUrlPubMedWeb of Science
  25. ↵
    Lieberman EH, Gerhard MD, Uehata A, Selwyn AP, Ganz P, Yeung AC, Creager MA: Flow-induced vasodilation of the human brachial artery is impaired in patients <40 years of age with coronary artery disease. Am J Cardiol 78:1210–1214, 1996
    OpenUrlCrossRefPubMedWeb of Science
  26. ↵
    Singh JP, Larson MG, O’Donnell CJ, Wilson PF, Tsuji H, Lloyd-Jones DM, Levy D: Association of hyperglycemia with reduced heart rate variability: the Framingham Heart Study. Am J Cardiol 86:309–312, 2000
    OpenUrlCrossRefPubMedWeb of Science
  27. ↵
    Tsuji H, Larson MG, Venditti FJ Jr, Manders ES, Evans JC, Feldman CL, Levy D: Impact of reduced heart rate variability on risk for cardiac events: the Framingham Heart study. Circulation 94:2850–2855, 1996
    OpenUrlAbstract/FREE Full Text
  28. ↵
    La Rovere MT, Pinna GD, Maestri R, Mortara A, Capomolla S, Febo O, Ferrari R, Franchini M, Gnemmi M, Opasich C, Riccardi PG, Traversi E, Cobelli F: Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patients. Circulation 107:565–570, 2003
    OpenUrlAbstract/FREE Full Text
  29. ↵
    Meigs JB, Mittleman MA, Nathan DM, Tofler GH, Singer DE, Murphy-Sheehy PM, Lipinska I, D’Agostino RB, Wilson PW: Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study. JAMA 283:221–228, 2000
    OpenUrlCrossRefPubMedWeb of Science
  30. ↵
    Kannel WB, D’Agostino RB, Wilson PW, Belanger AJ, Gagnon DR: Diabetes, fibrinogen, and risk of cardiovascular disease: the Framingham experience. Am Heart J 120:672–676, 1990
    OpenUrlCrossRefPubMedWeb of Science
  31. ↵
    Keaney JF Jr, Larson MG, Vasan RS, Wilson PW, Lipinska I, Corey D, Massaro JM, Sutherland P, Vita JA, Benjamin EJ: Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham study. Arterioscler Thromb Vasc Biol 23:434–439, 2003
    OpenUrlAbstract/FREE Full Text
  32. ↵
    Harris MI, Klein R, Welborn TA, Knuiman MW: Onset of NIDDM occurs at least 4–7 yr before clinical diagnosis. Diabetes Care 15:815–819, 1992
    OpenUrlAbstract/FREE Full Text
  33. ↵
    D’Agostino RB Sr, Grundy S, Sullivan LM, Wilson P: Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation. JAMA 286:180–187, 2001
    OpenUrlCrossRefPubMedWeb of Science
View Abstract
PreviousNext
Back to top
Diabetes Care: 27 (3)

In this Issue

March 2004, 27(3)
  • Table of Contents
  • About the Cover
  • Index by Author
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes Care.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
The Significant Effect of Diabetes Duration on Coronary Heart Disease Mortality
(Your Name) has forwarded a page to you from Diabetes Care
(Your Name) thought you would like to see this page from the Diabetes Care web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
The Significant Effect of Diabetes Duration on Coronary Heart Disease Mortality
Caroline S. Fox, Lisa Sullivan, Ralph B. D’Agostino, Peter W.F. Wilson
Diabetes Care Mar 2004, 27 (3) 704-708; DOI: 10.2337/diacare.27.3.704

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

The Significant Effect of Diabetes Duration on Coronary Heart Disease Mortality
Caroline S. Fox, Lisa Sullivan, Ralph B. D’Agostino, Peter W.F. Wilson
Diabetes Care Mar 2004, 27 (3) 704-708; DOI: 10.2337/diacare.27.3.704
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • RESEARCH DESIGN AND METHODS
    • RESULTS
    • CONCLUSIONS
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Tables
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Suboptimal Use of Cardioprotective Drugs in Newly Treated Elderly Individuals With Type 2 Diabetes
  • Disparities in Diabetes Care Between Smokers and Nonsmokers
  • Elevated Cystatin C Concentration and Progression to Pre-Diabetes
Show more Epidemiology/Health Services/Psychosocial Research

Similar Articles

Navigate

  • Current Issue
  • Standards of Care Guidelines
  • Online Ahead of Print
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.