Ndei Cardiovascular Disease In Diabetes Epidemiology

Epidemiology of CVD in Diabetes

Cardiovascular Disease and Type 2 Diabetes: An Update on Risks and Prevention

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This slide kit is intended to provide current information on issues concerning atherosclerosis and CVD in patients with type 2 diabetes.

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Disclosure

WHO Diabetes Estimates: 2000–2030 Number of Cases (in millions) Region 2000 2030 World > 170 > 363 Developed countries > 55 > 84 Developing countries > 114 > 279 Data adapted from Wild S et al. Diabetes Care . 2004;27:1047-1053. WHO=World Health Organization.

Type 2 Diabetes in the United States: Overview

Prevalence

18.2 million Americans (6.3% of the population)

13 million diagnosed

5.2 million not diagnosed

Additional 41 million adults aged 40-74 years are considered prediabetic

Incidence

1.3 million new cases diagnosed annually

Leading cause of

blindness in adults

end-stage renal disease

nontraumatic amputations

Healthcare costs $132 billion annually

90% to 95% of cases are type 2 diabetes CDC. National Diabetes Fact Sheet . www.cdc.gov/diabetes/pubs/general.htm. CDC. Diabetes: Disabling, Deadly, and on the Rise. 2004. www.cdc.gov/nccdphp/aag/pdf/aag_ddt2004.pdf .

Increasing Prevalence of Obesity* Among US Adults CDC. www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/index.htm. *BMI  30 kg/m 2 . 10%-14% 15%-19% 20%-24%  25% 1994 2002

Increasing Prevalence of Diagnosed Diabetes in US Adults CDC. www.cdc.gov/diabetes/statistics/prev/state/fig61994and2002.htm. 1994 2002 <4% 4%-4.9% 5%-5.9%  6%

Prevalence of the Metabolic Syndrome* in the US Population *As defined by the National Cholesterol Education Program. Age adjusted,  20 years of age. White African American Mexican American Other Prevalence (% of adults) 40 35 30 25 20 15 10 5 0 Men Women Ford ES et al. JAMA . 2002;287:356-359.

Relationship Between Type 2 Diabetes and the Metabolic Syndrome Metabolic Syndrome Type 2 Diabetes Data from Alexander CM et al. Diabetes . 2003;52:1210-1214.  44% of US adults aged >50 y have the metabolic syndrome (NHANES III) (13% without metabolic syndrome) 87% of patients with diabetes have the metabolic syndrome

Risk for Diabetes-Associated Conditions in People Aged <45 Years ADA. Diabetes Care . 1998;21:296-309. 11.5 10.3 7.4 5.4 4.8 4.3 2.8 1 5 10 15 CVD PVD Ophthalmic Neurologic Other chronic complications Renal General medical conditions Relative prevalence* Data are odds ratios. *Adjusted for race.

CHD in US Adults >50 Years of Age by Metabolic Syndrome and Diabetes Status Alexander CM et al. Diabetes . 2003;52:1210-1214. CHD=coronary heart disease. MetS=metabolic syndrome. T2D=type 2 diabetes. % of total population 54.2 28.7 2.3 14.8 CHD prevalence (%) 0 5 10 15 20 25 No MetS/No T2D T2D/No MetS T2D/MetS 8.7 13.9 7.5 19.2 MetS/No T2D

Complications of Diabetes: Contribution to Excess Healthcare Costs* Other care (59.1%) Acute complications (3.3%) Other vascular disease (1.3%) Stroke (3.7%) ESRD (10.6%) Amputation (3.7%) CHD (17.1%) Eye (1.2%) Selby JV et al. Diabetes Care . 1997;20:1396-1402. Total excess: $282.7 million Contribution of macrovascular complications: 22.1% ($62.5 million) *In a managed care population.

FRISC II: Diabetes Is the Most Important Independent Predictor of Death and MI Norhammar A et al. J Am Coll Cardiol . 2004;43:585-591. Age Gender Hypertension Diabetes Smoking Previous angina Previous MI ST-depression Troponin T >0.03  g/l 3-VD/LMD 0.98 0.80 1.31 2.40 0.96 1.22 1.85 1.22 1.66 1.06 RR (0.74-1.32) (0.64-0.99) (0.86-2.00) (1.47-3.91) (0.75-1.22) (0.87-1.72) (1.17-2.93) (0.80-1.86) (1.03-2.68) (0.84-1.33) NS 0.039 0.21 0.001 0.73 0.25 0.008 0.348 0.038 0.62 95% CI P 0.5 1 4 RR=risk ratio.

Reported Causes of Death in People With Diabetes Geiss LS et al. In: Diabetes in America . 2nd ed. 1995; chap 11. Data from death certificates. 0 10 20 30 40 50 Deaths (%) Ischemic heart disease Other heart disease Diabetes Cancer Stroke Infection Other

Mortality in People With Diabetes: Causes of Death ADA. Summary of the Report and Recommendations of the Congressionally Established Diabetes Research Working Group, 1999 . 140 120 100 80 60 1980 1984 1988 1992 1996 Year Age-adjusted death rate relative to 1980 Diabetes Cancer CVD Stroke

Mortality Associated With Metabolic Syndrome Data from Lakka H-M et al. JAMA . 2002;288:2709-2716. Mortality (% of patients) *Adjusted for known CHD risk factors.

Metabolic Syndrome Increases Cardiovascular and Total Mortality Data from Isomaa B et al. Diabetes Care . 2001;24:683-689. Mortality (%) P <0.001 P <0.001

Mortality Associated With Metabolic Syndrome Malik S et al. Circulation . 2004;110:1245-1250. Age- and gender-adjusted CHD, CVD, and total mortality rates in US adults with MetS with and without diabetes and pre-existing CVD in the NHANES II Follow-Up Study (n=6,255; mean follow-up, 13.3 years). MetS=metabolic syndrome; T2D=type 2 diabetes. 2.6 5.3 14.4 7.8 17.1 4.8 8.6 21.1 6.3 11.5 26.1 10.9 16.7 30.9 28.1 44.1 4.3 17.0 0 5 10 15 20 25 30 35 40 45 CHD mortality CVD mortality Total mortality Neither MetS nor T2D MetS w/o T2D MetS w/T2D T2D only Prior CVD Prior CVD and T2D Deaths/1,000 person-years

Seven-Year Incidence of Fatal/Nonfatal MI in Finland *No previous myocardial infarction (MI) at baseline. 0 5 10 15 20 25 30 35 40 45 50 7-Year incidence rate of MI (%) No previous MI* Previous MI No previous MI* Previous MI No diabetes Diabetes (n=1,373) (n=1,059) P <0.001 P <0.001 4 19 20 45 Haffner SM et al. N Engl J Med. 1998;339:229-234.

OASIS: Cardiovascular Disease Death in Patients With and Without Diabetes Malmberg K et al. Circulation . 2000;102:1014-1019. *RRs=crude relative risks, adjusted for age and sex (95% CI). OASIS=Organization to Assess Strategies for Ischemic Syndromes. 3 6 9 12 15 18 21 24 0.20 0.15 0.10 0.05 0.0 Months RR* = 2.85 (2.30-3.53) RR = 1.71 (1.41-2.06) RR = 1.71 (1.25-2.33) RR = 1.00 Diabetes/CVD (n=1,148) Diabetes/no CVD (n=569) No diabetes/CVD (n=3,503) No diabetes/no CVD (n=2,796) Event rate

MRFIT: Impact of Diabetes on Cardiovascular Disease Mortality Age-adjusted CVD death rate per 10,000 person-years 0 20 40 60 80 100 120 140 No diabetes Diabetes None One only Two only All three Number of risk factors Stamler J et al. Diabetes Care . 1993;16:434-444. MRFIT=Multiple Risk Factor Intervention Trial.

Risk of Stroke and MI Before and After Type 2 Diabetes Diagnosis No diabetes throughout the study Prior to diagnosis of diabetes After diagnosis of diabetes Diabetes at baseline Relative risk 0.0 1.0 2.0 3.0 4.0 5.0 6.0 1.0 2.82 3.71 5.02 Hu FB et al. Diabetes Care . 2002;25:1129-1134. MI=myocardial infarction.

Framingham Heart Study: Relative Risk of CVD in Patients With Diabetes Kannel WB et al. Am Heart J . 1990;120:672-676. * P <0.001; † P <0.05; ‡ P <0.01; § P <0.1. 0 1 2 3 4 5 6 Coronary mortality Sudden death Angina pectoris MI CHD Cardiac failure Intermittent claudication Stroke Any CVD event Age-adjusted risk ratio * § * † * † * † ‡ * † † Men Women ‡ CVD=cardiovascular disease.

Risk Factors for Cardiovascular Disease in Diabetes

Traditional risk factors

hypertension

dyslipidemia

obesity

smoking

family history of premature CVD

Nontraditional risk factors

insulin resistance

impaired fibrinolysis

microalbuminuria

endothelial dysfunction

markers of inflammation

abnormal homocysteine levels

postprandial abnormalities

vascular wall abnormalities

Fonseca V et al. Endocr Rev . 2004;25:153-175.

Components of the Metabolic Syndrome and Incidence of CHD Events 12 10 8 6 4 2 0 0 1 2 3 4 5 Years Patients with CHD event (%) 0 1 2 3 4/5 MetS Components Sattar N et al. Circulation . 2003;108:414-419. CHD=Coronary heart disease. MetS=metabolic syndrome.

IRAS: Relationship of Insulin Resistance to Atherosclerosis Change in IMT (  m) per 1-unit increase in S i Howard G et al. Circulation . 1996;93:1809-1817. P =0.002 P =0.001 P =0.003 P =0.097 P =0.586 P =0.178 IRAS=Insulin Resistance Atherosclerosis Study. S i =insulin sensitivity.

Paris Prospective Study 10-Year Follow-up: IGT and Risk of CHD Mortality Eschwège E et al. Horm Metab Res. 1985;15(suppl):41-46. CHD mortality (incidence rate/1,000 persons) G<140 mg/dL

5

4

3

2

1

0

IGT G  200 mg/dL (Newly diagnosed diabetes) Known diabetes

P <0.001

(6,055) (690) (158) (135) IGT=impaired glucose (G) tolerance.

Impaired Fasting Glucose Increases Risk of Mortality in CHD Patients 0.6 0.7 0.8 0.9 1.0 0 1 2 3 4 5 6 7 8 No diabetes IFG (100  125 mg/dL) Undiagnosed diabetes Actuarial survival Years Fisman EZ et al. Am Heart J . 2001;141:485-490. * P <0.01 vs no diabetes. † P <0.0001 vs no diabetes. * †

A1C Predicts Coronary Heart Disease in Type 2 Diabetes CHD mortality Incidence in 3.5 years All CHD events Incidence in 3.5 years A1C tertile A1C tertile * P <0.01 vs lowest tertile. † P <0.05 vs lowest tertile. Kuusisto J et al. Diabetes . 1994;43:960-967. Low <6% Middle 6-7.9% High >7.9% Low <6% Middle 6-7.9% High >7.9% * † % % 0 5 10 15 20 25 0 5 10 15 20 25

A1C Predicts Coronary Heart Disease in Type 2 Diabetes Data from Khaw KT et al. Ann Intern Med . 2004;141:413-420. CHD events (events/100 persons) A1C concentration *P <0.001 for linear trend across A1C categories.

Honolulu Heart Study: High Glucose Postchallenge Increases CHD Donahue RP et al. Diabetes . 1987;36:689-692. Adjusted for age, center, sex, cholesterol, BMI, SBP, smoking. 0 10 20 30 40 50 60 Fatal CHD Total CHD Postchallenge Glycemic Quintiles 40-114 mg/dL 115-133 mg/dL 134-156 mg/dL 157-189 mg/dL 190-532 mg/dL n=6,394 men without diabetes P <0.001 P <0.01 CHD risk per 1,000 patient-years

DECODE: Risk for All-Cause Mortality Fasting glucose (mg/dL) Hazard ratio Adjusted for age, center, sex, cholesterol, BMI, SBP, smoking. DECODE=Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe. Adapted from DECODE Study Group. Lancet . 1999;354:617-621. <110 110-125 126-139  140  200 140-199 <140 2-Hour OGTT

WESDR: Cause-Specific Mortality in Patients Aged  30 Years With Diabetes Moss SE et al. Arch Intern Med. 1994;154:2473-2479. *Adjusted for other risk factors, such as smoking and hypertension. WESDR=Wisconsin Epidemiologic Study of Diabetic Retinopathy. Cause of Death Increase in Hazard Ratio for Each 1% Increase in A1C* Ischemic heart disease 10% Stroke 17% Cancer -1%