EDITORIAL (SEE HOWARD ET AL., P. 391)

Diabetes and Coronary Risk Equivalency What does it mean?

he National Education who have but not CHD do not high enough risk that a simple tactic for Program Adult Treatment Panel III carry as high a risk for major coronary cholesterol-lowering therapy will be both T (ATP III) listed diabetes as a coro- events as do those with established CHD. efficacious and cost-effective. Even nary heart (CHD) risk equivalent Other studies (11–14) find that risk for though an individualized risk assessment for setting therapeutic goals for LDL cho- CHD is similar in patients with diabetes in patients with diabetes is reasonable in lesterol (1). A goal for LDL cholesterol of and those with established CHD. The ATP the hands of specialists, a broad applica- Ͻ100 mg/dl was recommended for pa- III report (1) indicated that diabetes in tion of risk assessment and adjustment of tients with CHD and CHD risk equiva- general can be viewed as a high-risk state goals for LDL cholesterol on a patient-by- lents. The latter included individuals with (CHD risk equivalent); this is generally patient basis by most practitioners will be noncoronary forms of atherosclerotic car- true and adds simplicity to cholesterol difficult to implement, just as it would be diovascular disease (ASCVD), diabetes, management, just as it does for patients in management of patients with ASCVD. and patients with a 10-year risk for major with established ASCVD. An alternate ap- Moreover, beyond the simplicity of coronary events ( ϩ proach is to attempt to estimate 10-year guidelines, several other reasons were coronary death) of Ͼ20%. For the major- risk for individuals with diabetes and to given in the ATP III report for identifying ity of patients with diabetes, this LDL cho- adjust LDL cholesterol goals accordingly. patients with diabetes as having a CHD lesterol goal would evoke the use of An example of individualized risk assess- risk equivalent. These reasons can be cholesterol-lowering drugs, particularly ment is the U.K. Prospective Diabetes summarized briefly. statins. Some investigators have ques- Study risk engine (15), which calculates First, in ATP III, CHD risk equiva- tioned whether most or all patients with risk for individuals with diabetes analo- lent defines the risk of developing a diabetes have a CHD risk equivalent and gous to the risk algorithm of the Framing- major coronary event (myocardial in- thus require cholesterol-lowering drugs ham Heart Study (8). Of interest, several farction ϩ coronary death) over 10 (2). One approach to this issue is to ex- reports suggest that Framingham scoring years of Ͼ20%. The 20% risk was that amine epidemiological data relating to ab- for patients with diabetes often underes- of patients with stable angina who have solute risk for developing CHD in various timates absolute risk (16–18). If so, the not sustained a myocardial infarction populations of persons with diabetes. choice of the risk assessment tool for es- (22,23). This risk is lower than for those In the present issue of Diabetes Care, timating risk for CHD becomes an impor- who have a history of acute myocardial Howard et al. (3) reported the tant issue when using an individualized infarction, which is about 26% (24,25). of CHD in the Strong Heart Study, a co- approach. Many subsequently assumed that the hort study of Of course, there is variability in risk risk accompanying a history of myocar- (CVD) in 13 American-Indian tribes/ for major coronary events in patients with dial infarction defined a CHD risk communities conducted in three study established CHD; therefore risk assess- equivalent and not stable angina. This centers in southwestern , cen- ment could be carried out in individuals was not the position of ATP III (1), tral , and North and South Da- with CHD to tailor secondary prevention which identified the 20% level. More- kota. The population of the Strong Heart therapies. This approach however has over, cost-effectiveness analysis showed Study has a high of type 2 di- been widely rejected by guideline panels that cholesterol-lowering drugs are abetes and CVD associated with diabetes. for CHD prevention (1,19–21). For most highly cost-effective at the risk level of The findings of this study showed wide cardiovascular guidelines, a diagnosis of 20% (1). In fact, as the costs of choles- variation in rates of CHD in patients with ASCVD triggers a full therapeutic re- terol-lowering drugs decline, accept- diabetes, depending in part on coexisting sponse for secondary prevention. The ra- able cost-effectiveness reaches down to risk factors. Most individuals had 10-year tionale is that the clinical simplicity of this 10% risk or even lower (1). risk Ͼ20%, the threshold for ATP III’s approach will yield a net benefit that ex- Beyond 10-year risk estimates, there CHD risk equivalency, but only those ceeds individual risk assessment based on were other reasons for applying the term with multiple risk factors had rates of problematic risk-assessment tools. This of CHD risk equivalent to patients with CHD events equivalent to patients with simplified strategy has been widely ac- diabetes. A common misconception is established CHD. The authors conclude cepted by the cardiovascular community that this term came exclusively from the that it may be prudent to consider thera- and appears to have improved implemen- study of Haffner et al. (11), which re- peutic goals for risk factors based on the tation of secondary prevention therapies. ported that Finnish patients with type 2 entire risk factor profile, rather than just The National Cholesterol Education diabetes have a risk for future major cor- the presence of diabetes. Program (1) proposed the same approach onary events similar to that of patients Other studies likewise have found for patients with diabetes who as a group with previous myocardial infarction. In considerable variability in risk for major are known to be at high risk for ASCVD ATP III, this was not the only rationale, coronary events when diabetes is present. events. The concept is that most patients although reference was made to this re- Some reports (4–10) suggest that patients with diabetes in the U.S. are at least at port (11) and others with similar findings

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(12,13). But other reports showed that mined. By the same token, how to sectional and cohort studies. BMJ 324: coronary mortality at time of acute myo- approach cholesterol-lowering therapy in 939–942, 2002 cardial infarction is essentially doubled in patients with type 1 diabetes in its earlier 5. Lottufo PA, Gaziano JM, Chae CU, Ajani patients with diabetes compared with stages is open to question (42). Most in- UA, Moreno-John G, Buring JE: Diabetes those without diabetes (26,27). More- vestigators do not favor use of cholesterol- and all cause and coronary heart disease mortality among US male physicians. over, in survivors of myocardial infarc- lowering drugs in early years of type 1 Arch Intern Med 161:242–247, 2001 tion, follow-up mortality in patients with diabetes, but as age advances, if LDL cho- 6. Hu FB, Stampfer MJ, Solomon CG, Liu S, diabetes is essentially doubled compared lesterol levels rise or if metabolic syn- Willett WC, Speizer FE: The impact of with persons without diabetes (28–34). drome becomes evident, cholesterol- diabetes mellitus on mortality from all ATP III contends that this high risk fol- lowering drugs become a reasonable causes and coronary heart disease in lowing onset of CHD justifies more inten- option. women: 20 years of follow up. Arch Intern sive primary prevention of ASCVD in The recent update of ATP III (45) Med 161:1717–1723, 2001 individuals with diabetes even if their 10- introduced the term high-risk to en- 7. Eberly LE, Cohen JD, Prineas R, Yang L: year risk is in the range somewhat below compass ATP III’s CHD and CHD risk Impact of incident diabetes and incident 20%. Other reasons can be cited for ele- equivalent category. This term may be non fatal cardiovascular disease on 18 year mortality: the Multiple Risk Factor vating the risk category when diabetes is less contentious and more generic. Intervention Trial experience. Diabetes present. For instance, patients with diabe- There appears to be increasing accep- Care 26:848–854, 2003 tes live on a higher trajectory of long-term tance of the concept that most patients 8. Wilson PWF, D’Agostino RB, Levy D, Be- risk than those without the disorder (35– with diabetes are at high risk for ASCVD langer AM, Silbershatz H, Kannel WB: 37). Several robust clinical trials, more- and that cholesterol-lowering therapy is Prediction of coronary heart disease using over, some of which were available at time an important component of risk reduc- risk factor categories. Circulation 197:1837– of the ATP III report (1), have docu- tion in this risk category. Acceptance of 1847, 1998 mented benefit of statin therapy in pa- this term may dampen some of the dis- 9. Cullen P, von Eckardstein A, Assmann G: tients with diabetes (38–41). These trials pute as to whether diabetes is a CHD Diagnosis and management of new car- have reassured many clinicians that more risk equivalent. diovascular risk factors. Eur Heart J 19 intensive cholesterol-lowering therapy is (Suppl. O):O13–O19, 1998 10. UK Prospective Diabetes Study Group: warranted when diabetes is present. SCOTT M. GRUNDY, MD, PHD Tight blood pressure control and risk of Recently, Alexander et al. (42) re- macrovascular and microvascular com- ported from the National Health and Nu- From the Center for Human Nutrition and Depart- plications in : UKPDS 38. trition Examination Survey (NHANES) III ments of Clinical Nutrition and Internal Medicine, BMJ 317:703–713, 1998 University of Texas Southwestern Medical Center at that persons with diabetes who have con- Dallas, Dallas, Texas. 11. Haffner SM, Lehto S, Ro¨nnemaa T, comitant metabolic syndrome, as defined Address correspondence to Dr. Scott M. Grundy, Pyo¨ra¨la¨ K, Laakso M: Mortality from cor- by ATP III, are the ones who are at highest Center for Human Nutrition and Departments of onary heart disease in subjects with type 2 risk. In fact, in patients without metabolic Clinical Nutrition and Internal Medicine, University diabetes and in nondiabetic subjects with syndrome, diabetes conferred very little of Texas Southwestern Medical Center at Dallas, and without prior myocardial infarction. 5323 Harry Hines Boulevard, Y3.206, Dallas, TX N Engl J Med 339:229–234, 1998 increased risk for major coronary events. 75390-9052.E-mail:scott.grundy@utsouthwestern. ϳ 12. Malmberg K, Yusuf S, Gerstein HC, In NHANES, 86% of patients with type edu. Brown J, Zhao F, Hunt D, Piegas L, Calvin © 2006 by the American Diabetes Association. 2 diabetes over age 50 years had meta- J, Keltai M, Budaj A, the OASIS Registry bolic syndrome (43). The findings of Investigators: Impact of diabetes on long- Howard et al. (3) are consistent with the ●●●●●●●●●●●●●●●●●●●●●●● term prognosis in patients with unstable NHANES III findings; patients with mul- References angina and non-Q-wave myocardial in- tiple metabolic risk factors were those at 1. National Cholesterol Education Program farction: results of the OASIS (Organiza- highest risk. In other words, hyperglyce- (NCEP) Expert Panel on Detection, Eval- tion to Assess Strategies for Ischemic mia in the absence of other risk factors did uation, and Treatment of High Blood Syndromes) Registry. Circulation not impart much increased risk for CVD Cholesterol in Adults (Adult Treatment 102:1014–1019, 2000 over the short term. This particularly is Panel III): Third Report of the National 13. 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Results Thus, for those who are uncomfortable 642, 2004 from 25 years of follow-up in the Renfrew with the generalized approach recom- 3. Howard BV, Best LG, Galloway JM, and Paisley Survey. Diabetes Care 28: mended by ATP III, an alternative strategy Howard WJ, Jones K, Lee ET, Ratner RE, 1588–1593, 2005 at least would be to count diabetes to- Resnick HE, Devereux RB: Coronary heart 15. Stevens R, Kothari V, Adler A, Stratton gether with metabolic syndrome as a disease risk equivalence in diabetes de- IM, Holman RR: UKPDS 56: the UKPDS pends on concomitant risk factors. Diabe- Risk Engine: a model for the risk of coro- high-risk condition worthy of intensive tes Care 29:391–397, 2006 nary heart disease in type 2 diabetes. Clin- cholesterol-lowering therapy. Whether 4. Evans JM, Wang J, Morris AD: Compari- ical Sci (Lond) 101:671–679, 2001 type 2 diabetes without the metabolic son of cardiovascular risk between pa- 16. 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