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Metabolic Syndrome Vs Framingham Risk Score for Prediction of Coronary Heart Disease, Stroke, and Type 2 Diabetes Mellitus

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Metabolic Syndrome Vs Framingham Risk Score for Prediction of Coronary Heart Disease, Stroke, and Type 2 Diabetes Mellitus ORIGINAL INVESTIGATION Metabolic Syndrome vs Framingham Risk Score for Prediction of Coronary Heart Disease, Stroke, and Type 2 Diabetes Mellitus S. Goya Wannamethee, PhD; A. Gerald Shaper, FRCP; Lucy Lennon, MSc; Richard W. Morris, PhD Background: We sought to compare metabolic syn- ity of developing CVD or DM2 over 20 years increased drome (MetS) with the Framingham Risk Score (FRS) from 11.9% in those with no abnormalities to 31.2% in as predictors of coronary heart disease (CHD), stroke, those with 3 abnormalities to 40.8% in those with 4 or 5 and type 2 diabetes mellitus (DM2) in middle-aged men. abnormalities. The FRS was a better predictor of CHD and stroke than MetS but was less predictive of DM2. Areas Methods: A prospective study of 5128 men aged 40 to under the receiver-operating characteristic curves for FRS 59 years with no history of cardiovascular disease (CVD) vs the number of metabolic abnormalities were 0.68 vs (CHD or stroke) or DM2 drawn from general practices 0.59 for CHD, 0.60 vs 0.70 for DM2, and 0.66 vs 0.55 in 24 British towns and observed for 20 years. Metabolic for stroke (PϽ.001 for all). syndrome was defined as the presence of 3 or more meta- bolic abnormalities based on modified National Choles- Conclusions: Presence of MetS is a significant predic- terol Education Program criteria. tor of CVD and DM2 but is a stronger predictor of DM2 than of CHD. Although MetS does not predict CHD as Results: Men with MetS at baseline (26%) showed sig- well as the FRS, it serves well as a simple clinical tool for nificantly higher relative risk (RR) than men without MetS of developing CHD (RR, 1.64; 95% confidence interval identifying high-risk subjects predisposed to CVD or DM2. [CI], 1.41-1.90), stroke (RR, 1.61 95% CI, 1.26-2.06), and DM2 (RR, 3.57; 95% CI, 2.83-4.50). The probabil- Arch Intern Med. 2005;165:2644-2650 ETABOLIC SYNDROME disease (CHD) risk than other risk assess- (MetS), defined as a ments such as the Framingham Risk Score cluster of risk factors, (FRS), 3 recent US studies indicate that MetS including obesity, hy- isinferiortotheFRSinpredictingCHD.19,21,24 pertension,hyperglyce- Stern et al19 conclude that MetS is inferior to Mmia, and dyslipidemia,1 is becoming increas- established rules for the prediction of either ingly common because of the increasing DM2 or CVD, and the use of MetS as a fo- prevalenceofobesity.2 TheWorldHealthOr- cus of screening for metabolic risk modifi- ganization(WHO)Consultationin1998pro- cation has become questionable. Nonethe- vided a provisional definition for MetS3 and less, MetS predicts both CVD and DM2, and revised it in 1999.4 The Third Report of the since previous studies have not shown National Cholesterol Education Program whethertheFRSisagoodpredictorofDM2,25 (NCEP) Expert Panel on Detection, Evalu- MetS may be a good all-purpose predictor ation, and Treatment of High Blood Choles- compared with the FRS. Furthermore, there terol in Adults (Adult Treatment Panel III)5 have been few prospective studies on the re- presented a simpler definition of MetS in- lationship between MetS and risk of stroke. tended for the identification of people with We have assessed the prospective relation- the syndrome in clinical practice.6 Whether ship between MetS and risk of CHD, stroke, defined on the basis of NCEP criteria7-21 or and DM2 using a modified NCEP definition WHO criteria,8-10,13,18,22,23 MetS is associated andhavecomparedMetSwiththeFRSinpre- with significantly increased risk of develop- dicting risk over 20 years follow-up. ing type 2 diabetes mellitus (DM2) and car- diovascular disease (CVD) and has been METHODS widely promoted as a means of identifying Author Affiliations: Department of Primary Care patients for lifestyle intervention to reduce The British Regional Heart Study26 is a large pro- and Population Sciences, Royal risk factors and incident disease, in particu- spective study of CVD comprising 7735 men 24,25 Free and University College lar CVD. aged 40 to 59 years drawn from general prac- Medical School, While it has not been established whether tices in each of 24 towns in England, Wales, London, England. MetS is a better predictor of coronary heart and Scotland. The criteria for selecting the (REPRINTED) ARCH INTERN MED/ VOL 165, DEC 12/26, 2005 WWW.ARCHINTERNMED.COM 2644 ©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 towns, the general practices, and the subjects as well as the meth- FOLLOW-UP ods of data collection have been reported.26 Research nurses administered a standard questionnaire that included ques- All men were evaluated on follow-up for all-cause mortality, tions on lifestyle and medical history. The men were asked to cardiovascular morbidity, and development of DM2 from the recall a physician’s diagnosis of CHD (angina or myocardial in- initial screening in January 1978–July 1980 to June 2000, a mean farction), stroke, and DM2. Physical measurements including period of 21.3 years; follow-up was achieved for 99% of the co- height and weight were made, and venous nonfasting blood hort.35 This analysis is based on a 20-year follow-up for each samples were obtained for measurement of biochemical and he- man. Criteria for accepting a diagnosis of nonfatal myocardial matologic characteristics. Triglyceride measurements were only infarction, stroke, and death have been reported, as has the available for men in the seventh to 24th towns visited (n=5663). method for ascertaining new cases of DM2.27,36 A combined end Details of smoking history, alcohol use, physical activity, so- point was also used, defined as the confirmed development of cial class, blood pressure (BP), and blood lipid measurements have a heart attack, stroke, or DM2. been reported.26-28 Heavy drinking was defined as 6 alcoholic drinks daily or on each of most days in the week (1 drink=10 g of al- cohol). A physical activity (exercise) score was derived for each STATISTICAL ANALYSIS man, and the men were initially grouped into 6 broad categories based on their total score (none, occasional, light, moderate, mod- The Cox proportional hazards model was used to assess the ad- erately vigorous, or vigorous).27 Men who reported no or occa- justed relative risks (RRs). Receiver-operating characteristic sional physical activity were defined as “inactive.” Adjustments (ROC) curves and their respective areas under the curve (AUCs) were used to compare the ability of the FRS and the number of were made for the marked diurnal variation in serum triglycer- 37 ide concentration.29 Men with recall of a physician diagnosis of metabolic abnormalities to predict CHD and DM2. Tests for differences between the curves were performed using Stata soft- CHD or stroke, known diabetes at screening, and/or asymptom- 38 atic hyperglycemia (glucose level, Ն200 mg/dL [Ն11.1 mmol/L]) ware, version 9.0 (Stata Corp, College Station, Tex). were excluded (n=441). Data on MetS were not available in 94 men. After these exclusions, data were available for a group of RESULTS 5128 men, the subjects of this study. During the 20-year follow-up, there were 763 major CHD DEFINITION OF MetS events (fatal CHD and nonfatal myocardial infarction), Metabolic syndrome as defined by NCEP5 comprises 3 or more 291 major stroke events (fatal and nonfatal), and 299 cases of the following: (1) fasting plasma glucose level of at least 110 of DM2 in the 5128 men with no history of CHD, stroke, mg/dL (6.1 mmol/L); (2) serum triglyceride level of at least 150 or diabetes. Table 1 lists the baseline characteristics in mg/dL (1.7 mmol/l); (3) serum high-density lipoprotein cho- these men. Metabolic syndrome was present in over a lesterol level lower than 40 mg/dL (1.04 mmol/L); (4) BP of at quarter of the men (26.0%); 53.9% of men who devel- least 130/85 mm Hg or controlled with antihypertensive treat- oped DM2 had MetS at baseline compared with 35.5% ment; and/or (5) waist circumference of more than 102 cm.5 of the men developing CHD and 34.7% of the men who Waist circumference was not measured in the present study. developed stroke. Metabolic syndrome was associated with However, in a subset of 3000 of these men whose waist cir- a significant increase in CHD, stroke, and particularly DM2 cumference and body mass index (BMI) (calculated as weight after adjustment for age, social class, smoking status, in kilograms divided by the square of height in meters) were measured 20 years after initial screening, regression analysis physical activity level, and alcohol use (Table 2). Risk showed a BMI of 28.9 to be equivalent to a waist circumfer- of CHD and DM2 increased significantly with increas- ence of 102 cm, similar to analysis using data from a large US ing number of components of MetS (Table 3). The re- survey.30 We have therefore used a BMI of 28.8 or higher as a lationship with stroke was less consistent. proxy for abdominal adiposity in conformity with other stud- When the higher thresholds for nonfasting glucose were ies that have used BMI to replace waist circumference.7 used for the definition of high blood glucose level in MetS Sincetriglyceridelevelswerebasedonnonfastingmeasurements, (ie, Ն126 mg/dL (Ն7.0 mmol/L) and Ն140 mg/dL (Ն7.8 which are on average 20% to 30% higher than fasting levels,31 we mmol/L), this slightly attenuated the RR of CHD associ- have used a higher threshold and defined high triglyceride level Ն ated with MetS (RR, 1.57; 95% confidence interval [CI], as greater than or equal to 200 mg/dL ( 2.28 mmol/L).
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