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Screening for coronary heart disease in patients with diabetes mellitus

Screening for coronary heart disease in patients with diabetes mellitus
Authors:
Jeroen J Bax, MD, PhD
Frans J Th Wackers, MD, PhD
Victoria Delgado, MD, PhD
Section Editors:
David M Nathan, MD
Patricia A Pellikka, MD, FACC, FAHA, FASE
Deputy Editor:
Jane Givens, MD, MSCE
Literature review current through: Nov 2022. | This topic last updated: Jul 08, 2022.

INTRODUCTION — Diabetes mellitus is associated with an approximately twofold increased risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD) mortality, as shown in a meta-analysis of 102 prospective studies including 698,782 individuals (hazard ratio [HR] 2.0, 95% CI 1.8-2.2) [1]. Diabetes frequently coexists with other cardiovascular risk factors such as hypertension and dyslipidemia, sometimes known as the metabolic or cardiometabolic syndrome. However, diabetes mellitus confers an increased risk for cardiovascular events independent of other traditional risk factors [2]. (See "Type 2 diabetes mellitus: Prevalence and risk factors", section on 'Prevalence'.)

Patients with diabetes and noncoronary atherosclerotic disease have a higher risk of CHD than patients with diabetes but no known vascular disease and thus require a different diagnostic approach. Such patients should have appropriate aggressive individualized diagnostic workup. (See "Overview of established risk factors for cardiovascular disease", section on 'Noncoronary atherosclerotic disease' and "Outpatient evaluation of the adult with chest pain".)

In nearly all patients with diabetes, the results of screening will generally not change medical therapy, since aggressive preventive measures, such as control of blood pressure and lipids, would already be indicated. However, the use of low-dose aspirin may not be warranted in all asymptomatic diabetic patients, since >30 percent of asymptomatic diabetic patients may not have CHD, and the use of coronary artery calcium (CAC) score could be considered as a measure to detect/exclude CHD. (See 'Screening issues' below and 'Computed tomography' below.)

Issues related to the detection of coronary atherosclerosis and ischemia, as well as the studies related to screening for CHD in patients with diabetes, will be reviewed here. The epidemiology of CHD in patients with diabetes and the data related to screening for CHD in the general population are discussed separately. (See "Prevalence of and risk factors for coronary heart disease in patients with diabetes mellitus" and "Screening for coronary heart disease".)

EPIDEMIOLOGY — Whether the patient suffers from type 1 or type 2 diabetes, along with the patient's age and duration of time living with diabetes, will impact the risk for developing cardiovascular disease (CVD), as diabetes itself is a powerful risk factor for the future development of CVD. In patients with type 1 diabetes, CVD becomes the leading cause of death after 10 years of duration and accounts for 40 percent of all deaths after 20 years of duration [3]. Most studies on cardiovascular risk in patients with diabetes have been performed in patients with type 2 diabetes, who are typically older at disease onset than those with type 1 diabetes.

Although the study results are not all consistent, several studies have suggested that patients with type 2 diabetes without known coronary heart disease (CHD) have at least similar (if not higher) risk of cardiovascular mortality as patients without diabetes who had prior myocardial infarction (MI) or known CHD [1,2,4]. As an example, in a meta-analysis that included 698,782 patients (from 102 prospective studies) with no known history of CHD, MI, angina, or stroke, diabetes was associated with a significantly increased risk of CHD, stroke, and other vascular disease (adjusted hazard ratio [HR] for CHD 2.0, 95% CI 1.8-2.2) [1]. While the incidence of CHD has declined over time with improvements in risk factor modification, diabetes appears to persist as a significant risk factor for CHD [2].

By contrast, other large observational studies have not supported the concept of diabetes as a CHD-equivalent [4-7]. The disparate results across studies are likely explained by differences in patient populations, follow-up duration, lifetime risk, or use of lipid-lowering and other primary prevention therapies [2]. Data from the Swedish National Diabetes Register including 271,174 patients with type 2 diabetes showed that having five risk factors within guideline-recommended target ranges was associated with little or no excess risk of death, MI, or stroke, as compared with the general population [7]. (See "Overview of established risk factors for cardiovascular disease", section on 'Diabetes mellitus' and "Prevalence of and risk factors for coronary heart disease in patients with diabetes mellitus", section on 'Diabetes as a CHD equivalent'.)

Age and duration of diabetes play a role in the risk for developing CVD in patients with diabetes as in the general population. Among a retrospective, population-based cohort study of over 9 million adults (379,000 with diabetes), the transition to high cardiovascular risk (10-year event rate risk of greater than 20 percent) among persons with diabetes occurred at age 41 years in men and 48 years in women, approximately 15 years earlier than in individuals without diabetes [8]. In a smaller prospective study of 5934 men (285 with diabetes, mean age 63 years) who were followed for 10 years, risk of CHD events increased with increasing duration of diabetes, and risk of CHD in patients with diabetes for 12 or more years was equivalent to the CHD risk for patients with prior MI and no diabetes [5].

Accordingly, various professional societies from the United States and Europe, who publish guidelines and recommendations, consider patients with type 2 diabetes to be at high risk for CHD [9-12]. These observations are consistent with the American Diabetes Association practice guideline, which considered the transition to high cardiovascular risk to occur above age 40 in patients with both type 2 and type 1 diabetes [13]. (See 'Recommendations of professional societies' below.)

PREVALENCE OF ASYMPTOMATIC CHD — Asymptomatic coronary heart disease (CHD) in patients with diabetes includes lesions that are insufficient to produce ischemia and those that can produce ischemia (eg, with exercise or pharmacologic stress) but may not be appreciated clinically by the patient. Some patients with diabetes have a blunted appreciation of ischemic pain, which may result in atypical anginal symptoms, silent ischemia, or even silent myocardial infarction (MI). Silent ischemia in diabetes is thought to be caused at least in part by autonomic denervation of the heart. These issues are discussed in detail separately. (See "Prevalence of and risk factors for coronary heart disease in patients with diabetes mellitus", section on 'Silent ischemia and infarction' and "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis".)

The prevalence of asymptomatic CHD in patients with diabetes depends significantly on the method of screening and what test result is considered diagnostic for CHD. The presence of asymptomatic CHD has been evaluated in a variety of ways. These include assessment with computed tomography (CT; either for coronary artery calcification (CAC) or to assess coronary artery stenosis), stress testing to detect silent ischemia, and invasive coronary angiography.

Computed tomography — Electron beam CT scan and multidetector row CT (MDCT) can noninvasively detect the presence of CAC and coronary artery atherosclerosis. CAC scanning estimates the total atherosclerotic burden but is not necessarily predictive of significant coronary artery stenosis. Additionally, noninvasive CT coronary angiography can detect coronary stenoses with a high degree of accuracy. (See "Coronary artery calcium scoring (CAC): Overview and clinical utilization".)

The frequency and potential clinical importance of coronary atherosclerosis in patients with diabetes who have no defined CHD is illustrated by the following findings:

Across age groups, asymptomatic adults with diabetes have higher median CAC scores on electron-beam CT scanning than individuals without diabetes [14-17]. In young asymptomatic individuals (<40 years), the presence of diabetes was associated with fourfold higher odds of having moderate-severe CAC (Agatston score ≥100) compared with patients without diabetes [17]. However, a meta-analysis of eight studies (6521 patients) revealed that 29 percent had a CAC score <10, indicating that nearly 3 in 10 patients had very little or no calcified coronary artery atherosclerosis [16].

Coronary artery calcification does not usually result in ischemia in asymptomatic patients, even in those with diabetes [18,19].

In a substudy of the CONFIRM registry, which included 400 asymptomatic patients with diabetes and no prior history of CHD, 30 percent of patients had no CHD on coronary CT angiography, while 27.8 percent showed at least one coronary artery with stenosis of 50 percent or more [20].

A meta-analysis including eight studies and 6225 patients with diabetes without known CHD (67 percent asymptomatic) reported that 25 percent of patients did not have CHD, while 38 percent had obstructive CHD [21].

In a study of 607 asymptomatic patients with type 2 diabetes who underwent coronary CT angiography, 188 patients (31 percent) had at least one coronary artery with a stenosis of 50 percent or greater [22].

Stress testing — Patients with type 2 diabetes, who are generally older than patients with type 1 diabetes, more frequently have silent ST segment depression and coronary perfusion abnormalities during stress testing, with the prevalence estimated at between 20 and 40 percent in most prospective cohorts [19,23-27]. In contrast to the findings in most prospective trials, large retrospective analyses of cohorts of asymptomatic patients with diabetes have reported higher rates of abnormal stress tests (40 to 60 percent) [28-30] and high-risk findings (approximately 20 percent) [28,30], likely due to referral bias. The presence of silent myocardial ischemia appears similar when either radionuclide myocardial perfusion imaging (rMPI) or dobutamine stress echocardiography is used [31]. As examples:

In the prospective DIAD study of 1123 asymptomatic patients with type 2 diabetes (age 50 to 75 years), of whom 522 patients were assigned to adenosine stress rMPI, silent ischemia was seen in 22 percent of patients, with large defects identified in 6 percent [26].

Similarly, in the DYNAMIT trial, which randomized 631 asymptomatic patients with type 2 diabetes (mean age 64 years) with at least two additional cardiovascular risk factors to screening for silent myocardial ischemia (exercise electrocardiogram [ECG] test or dipyridamole rMPI) or to conventional medical treatment, the prevalence of silent myocardial ischemia was 21.5 percent [32].

In the BARDOT trial, which included 400 asymptomatic patients with type 2 diabetes who underwent rest- and stress-gated rMPI, the prevalence of silent ischemia was 22 percent [27].

SCREENING ISSUES — As discussed, coronary heart disease (CHD) is a frequent and significant health issue for patients with diabetes. Intuitively, screening to detect early CHD and provide targeted treatment for patients with evidence of CHD would seem reasonable. However, as with screening for any condition, there are multiple issues that must be addressed concerning the possible role of screening for CHD in such patients (eg, the accuracy of screening tests, how easily testing can be performed, the safety of testing, costs of testing, available interventions that improve outcomes, etc). The general approach to screening is discussed in detail separately. (See "Evidence-based approach to prevention".)

Purpose of screening — As with screening for any condition, the primary purpose of screening for CHD in patients with diabetes would be to identify patients whose prognosis could be improved with an intervention (in this case, medical therapy for risk factors or coronary revascularization). In nearly all patients with diabetes, the results of screening will generally not change medical therapy, since aggressive preventive measures, such as control of blood pressure and lipids, would already be indicated [33]. In the case of low-dose aspirin, there are real risks of gastrointestinal bleeding, so detection of CHD by screening would justify the therapy and alter the risk-benefit ratio in favor of aspirin use in most patients [34,35]. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus" and "Treatment of hypertension in patients with diabetes mellitus" and "Overview of established risk factors for cardiovascular disease", section on 'Diabetes mellitus'.)

Screening tests for CHD diagnosis — How diabetes affects the diagnostic yield of exercise electrocardiogram (ECG) stress testing is not well defined, and there are particularly few data available in asymptomatic patients with diabetes [36]. In one study of 1282 men without prior myocardial infarction (MI) who had undergone exercise ECG testing and coronary angiography, the sensitivity and specificity for CHD were 47 and 81 percent in patients with diabetes (compared with 52 percent sensitivity and 80 percent specificity in patients without diabetes) [37]. The characteristics of screening tests are presented in the table (table 1).

The accuracy of exercise testing and imaging modalities to diagnose CHD applied in the general population has been summarized in a 2018 meta-analysis, however, the patients were largely referred for testing because CHD was suspected; as a result, the findings may not apply to a screening population [38].

Stress testing with radionuclide myocardial perfusion imaging (rMPI) is more sensitive than exercise stress testing alone for the diagnosis of CHD [39]. The test performance of exercise or adenosine stress single-photon emission computed tomography (SPECT) rMPI was evaluated in 326 patients (138 patients with diabetes) without prior MI or revascularization (only 50 percent had symptoms of angina) who had coronary angiography within six months of the stress test [39]. Among patients with diabetes, the sensitivity and specificity of SPECT rMPI were 86 and 56 percent for ≥50 percent diameter stenosis and 90 and 50 percent for ≥70 percent diameter stenosis. Test performance was similar with exercise and adenosine and in the patients without diabetes. (See "Overview of stress radionuclide myocardial perfusion imaging" and "Stress testing for the diagnosis of obstructive coronary heart disease".)

Stress echocardiography has similar diagnostic accuracy for CHD as stress testing with rMPI [40,41]. In a separate review of 128 patients with diabetes who had a dobutamine stress myocardial contrast echocardiography and also underwent coronary angiography, the sensitivity and specificity for obstructive CHD were 89 and 52 percent, respectively [41]. (See "Overview of stress echocardiography" and "Contrast echocardiography: Clinical applications".)

Many studies have demonstrated the prognostic value of coronary artery calcification (CAC) scoring in patients with diabetes, but few have addressed the diagnostic ability of CAC; importantly, CAC scoring does not allow differentiation between obstructive and nonobstructive CHD. In addition, a CAC score of 0 does not completely exclude CHD [42]. Noninvasive coronary angiography can be performed with either multidetector CT (MDCT) or magnetic resonance imaging (MRI) techniques [43-45]. A meta-analysis of nine studies including 2756 patients undergoing CT coronary angiography showed a sensitivity and specificity of 97 and 78 percent to detect ≥50 percent stenosis on invasive coronary angiography [38]. (See "Cardiac imaging with computed tomography and magnetic resonance in the adult".)

Screening tests for CHD prognosis — Combined testing with exercise stress and an imaging procedure (echocardiography or rMPI) provides incremental risk stratification in patients with (and without) diabetes [46]. With respect to screening for CHD, identifying patients at high risk could be an important component since these are the patients in whom intervention would likely have the greatest benefit. These issues in the general population of patients who undergo stress testing are discussed in detail separately but will be summarized briefly here. (See "Screening for coronary heart disease".)

In terms of prognosis, patients are generally classified into three categories based upon estimated annual cardiac mortality:

Low risk – Less than 1 percent per year

Moderate risk – 1 to 3 percent per year

High risk – More than 3 percent per year

However, as noted below, the good prognosis of a low-risk test may not apply to patients with diabetes after the first two years. (See 'Low-risk stress tests' below.)

Exercise stress, if possible, is preferred since the response to exercise itself has prognostic value. Unfavorable prognostic signs include poor exercise capacity (<5 metabolic equivalents [METs]); exercise-induced angina; abnormally low peak systolic blood pressure (<130 mmHg) or a fall in the systolic blood pressure during exercise; and chronotropic incompetence, as well late heart rate recovery. Other important indicators of prognosis include the Duke treadmill score during exercise testing, stress-induced left ventricular dysfunction or the number of vascular territories with wall motion abnormalities on stress echocardiography, and the number of vascular territories with perfusion defects on rMPI [47]. (See "Overview of stress radionuclide myocardial perfusion imaging" and "Overview of stress echocardiography" and "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Duke treadmill score'.)

In both stress rMPI and stress echocardiography, the majority of the available data regarding prognosis in patients with diabetes comes from symptomatic patients [28,29,47-54]. As an example, in a study of 1737 patients with diabetes and without known CHD (of which 826 were asymptomatic), the annual rate of cardiac death or nonfatal MI was significantly higher in patients with an abnormal stress rMPI, with event rates that were similar in asymptomatic patients and those with angina [29].

Low-risk stress tests — Patients with a normal stress test generally have an annual mortality rate below 1 percent, but it is unknown how long this low event rate persists, particularly in patients with diabetes. The applicability of this relationship for patients with diabetes has been evaluated in several studies, but again most of the available data relate to symptomatic patients.

In a study of 4755 patients (929 with diabetes) with symptoms of CHD who underwent stress rMPI, cardiac mortality was low in patients with a normal stress rMPI, with equivalent rates in patients with and without diabetes for the first two years [54]. However, after two years, there was a sharp increase in cardiac events in the patients with diabetes.

Similarly, in a cohort of 563 patients with diabetes (59 percent with symptoms of CHD), cardiac mortality or MI were not observed within the first two years after a normal exercise echocardiogram but subsequently occurred in 1.8 percent of patients at year 3, with increasing event rates thereafter [47].

In a meta-analysis of 14 studies (13,493 patients), the negative predictive value for non-fatal MI or cardiac death of a normal rMPI was 95 percent, with a corresponding annualized event rate of 1.6 percent [55].

The worse outcomes in patients with diabetes over longer time could reflect more rapid progression of atherosclerosis [56]. Such observations have led to the suggestion that the "warranty period" of a normal stress imaging test may be limited in high-risk patients (such as those with diabetes) and that repeat testing after two years may be required in such patients [57]. Results from the DIAD study, however, suggested that the warranty period of a normal stress rMPI may be longer [26,58]. (See 'Does screening for subclinical CHD improve outcomes?' below.)

CAC scanning — The CAC score adds independent prognostic information in asymptomatic individuals to that determined by the Framingham risk calculators. Given this incremental value, screening for CAC could represent an initial screening approach, with referral for stress testing with rMPI or echocardiographic imaging as the next step in patients with severe atherosclerosis (CAC score >400) [48,59]. However, such an approach cannot be recommended without some evidence that outcomes are improved. (See "Cardiovascular disease risk assessment for primary prevention: Risk calculators".)

The majority of large observational studies have reported that the CAC score predicts all-cause mortality in patients with diabetes, with an increase in mortality for every increment in CAC score [60-62]. In the Diabetes Heart Study, 1051 patients with diabetes had CT scans performed and were followed for over seven years; patients with a CAC score <10 had a 0.9 percent annual mortality, as compared with 2.7 percent in patients with a CAC score ≥1000 [60]. In a meta-analysis of eight studies (including 6521 patients with type 2 diabetes; mean follow-up of 5.2 years), there was a significantly higher risk of all-cause mortality and/or cardiovascular events in patients with a CAC ≥10 (relative risk 5.5, 95% CI 2.6-11.5) [16]. Importantly, for patients with a score <10, the post-test probability of the combined endpoint of all-cause mortality and cardiovascular events was 1.8 percent, which was a 6.8-fold reduction from the pretest probability, indicating that CAC scoring can reclassify risk of patients with diabetes. However, at long-term follow-up, the mortality risk increases among patients with diabetes even in the presence of a baseline CAC score of 0 [63]. In an observational study of 9715 asymptomatic individuals undergoing CAC scoring and 15 years of follow-up, patients with diabetes and CAC score 0 (n = 275) had a 2.5 increased hazard of all-cause mortality compared with patients without diabetes (n = 4589) [63]. These results suggest that the risk of asymptomatic individuals with diabetes changes over time, and close monitoring and strict treatment of associated cardiovascular risk factors should be intensified. Data from the Multi-Ethnic Study of Atherosclerosis (3116 persons, 8.8 percent with diabetes, with CAC score 0 and at least one repeat CAC scan) showed that the warranty period of CAC score 0 in patients with diabetes was 38 percent shorter in women (4.3 versus 6.9 years) and 35 percent shorter in men (3.1 versus 4.8 years) as compared with individuals of the same sex without diabetes [64]. Whether repeat CAC scoring would have an impact on the treatment and prognosis of these patients remains unclear. (See "Coronary artery calcium scoring (CAC): Overview and clinical utilization", section on 'Follow-up based on CAC score'.)

CT angiography — In a study of 3370 patients with diabetes and 6740 propensity matched patients (mean follow-up 2.2 years) that evaluated the prognostic value of MDCT coronary angiography, mortality was significantly higher in patients with diabetes with both non-obstructive and obstructive CHD (compared with patients without diabetes) [65]. Of interest, in 400 asymptomatic patients with diabetes, the incremental prognostic value of MDCT coronary angiography over CAC score was shown [20]. Additional comparative studies are needed to determine the relative prognostic values of CT angiography and CAC score.

DOES SCREENING FOR SUBCLINICAL CHD IMPROVE OUTCOMES? — To justify screening for subclinical coronary heart disease (CHD) in patients with diabetes, the prevalence of CHD and the accuracy of the screening test should be high, and intervention should improve outcomes. Studies have shown that the prevalence of silent CHD ranges between 11 and 60 percent, with the wide range of prevalence likely related to different patient characteristics (ie, age, abnormal baseline electrocardiogram [ECG], other risk factors) and whether the study was prospective or retrospective [19,20,23-25,27,31,32,42,58,66-69]. Several prospective randomized trials have evaluated the impact of routine screening for subclinical CHD and the effect of therapy on outcomes of asymptomatic patients with type 2 diabetes, with no significant improvement in outcomes among patients who underwent screening [32,58,67,70,71]. As such, we do not routinely screen for CHD in asymptomatic diabetic patients.

In a study of 1123 asymptomatic patients with type 2 diabetes conducted between 2000 and 2007 in the United States, the DIAD investigators randomized patients with a normal resting ECG and no clinical evidence of CHD to either screening with adenosine-stress radionuclide myocardial perfusion imaging (rMPI) or no screening [26,58]. In the group screened with adenosine rMPI, the overall prevalence of silent myocardial ischemia was 22 percent, with high-risk imaging results (defined as perfusion defects of at least 5 percent of the myocardium) in only 6 percent. After a mean follow-up of 4.8 years, there was no significant difference in the primary endpoints (cardiac death or nonfatal myocardial infarction [MI]) between the screening and no-screening groups (2.7 versus 3.0 percent, respectively).

In a study of 631 asymptomatic patients with type 2 diabetes and at least two other CHD risk factors conducted between 2000 and 2005 in France, the DYNAMIT investigators randomized patients to either screening with rMPI or no screening; symptom-limited bicycle exercise was the primary stress modality, although 31 percent of patients had pharmacologic stress due to inability to exercise adequately [32]. In the screened group, the prevalence of silent myocardial ischemia was 21.5 percent, similar to the DIAD study. After a mean follow-up of 3.5 years, there was no significant difference in the composite primary endpoint (death from all causes, nonfatal MI, nonfatal stroke, or heart failure requiring emergency intervention) outcomes between the screening group and no-screening group (2.6 versus 2.4 percent annually; adjusted hazard ratio [HR] 1.0, 95% CI 0.6-1.7).

In contrast to the DIAD and DYNAMIT trials, in which the screening of asymptomatic patients with type 2 diabetes was based on the identification of significant CHD causing myocardial ischemia, the FACTOR-64 trial, conducted between 2007 and 2014 in the United States, evaluated the extent and severity of coronary atherosclerosis using coronary computed tomography (CT) angiography and provided specific treatment based on the CT results [70]. FACTOR-64 included 900 asymptomatic patients with type 1 or 2 diabetes who were randomized to coronary CT angiography screening or no screening. Among patients randomized to CT coronary angiography screening, the prevalence of mild, moderate, and severe CHD was 31, 46, and 12 percent, respectively. After a mean follow-up of four years, there was no significant difference in the primary endpoint (composite of all-cause mortality, non-fatal MI, or unstable angina) following screening with coronary CT angiography (6.2 versus 7.6 percent without screening, HR 0.8, 95% CI 0.5-1.3).

The DADDY-D trial, conducted between 2007 and 2012 in a single center in Italy, randomized 520 patients with type 2 diabetes without known CHD and cardiovascular risk score ≥10 percent to screening with exercise ECG versus no screening [71]. Silent myocardial ischemia was documented in 20 (7.6 percent) patients and coronary revascularization was performed in 12 (4.6 percent). Over a median follow-up of 3.6 years, there were no differences in the occurrence of cardiovascular death, nonfatal MI, or the combination of both endpoints.

A meta-analysis of five randomized studies, including 3314 patients with diabetes, showed that the screening strategy did not have an impact on all-cause mortality (odds ratio [OR] 1.00, 95% CI 0.67-1.50), with nonsignificant trends toward lower risk of cardiovascular death (OR 0.71, 95% 0.40-1.27), and nonfatal MI (OR 0.60, 95% CI 0.23-1.52) [72].

Complementary to previous trials, the BARDOT trial evaluated the prognostic implications of medical versus invasive treatment in asymptomatic patients with type 2 diabetes and abnormal screening test results [27]. In this study of 400 asymptomatic patients with type 2 diabetes at high risk for CHD conducted between 2004 and 2010 in Switzerland and Germany, all patients underwent stress rMPI, which identified silent ischemia in 22 percent, similar to the DIAD and DYNAMIT trials [27]. The 87 patients with abnormal stress rMPI were then randomized to medical therapy alone versus medical therapy plus invasive coronary revascularization, providing additional data on the effect of these therapies on the outcome of asymptomatic patients. The primary outcome was a combination of major adverse cardiac events and worsening rMPI findings at two-year follow-up. While there was a trend toward reduction in the primary outcome with the invasive therapy group, this was not statistically significant, possibly due to low numbers of patients and events.

It should be emphasized that these outcomes apply to asymptomatic patients with type 2 diabetes without known clinical CHD on contemporary optimal medical therapy (ie, optimal glycemic control and optimal treatment of hypertension and dyslipidemia). In addition, many patients enrolled in these studies were on primary CHD prevention with aspirin, statins, and angiotensin-converting enzyme (ACE) inhibitors, the protective effect of which has been shown in the DIAD study, when the majority of patients showed resolution of ischemia on repeat rMPI at three years’ follow-up [73,74]. It should also be emphasized that assessment of CHD by coronary artery calcium (CAC) score may still be relevant since patients without CHD will not benefit from low-dose aspirin, which is clinically important since >27 percent of asymptomatic diabetic patients may not have CHD [34,35,75]. (See 'Computed tomography' above.)

ROLE OF RISK ENGINES TO DEFINE CARDIOVASCULAR RISK — A number of multivariate risk models have been developed for estimating the risk of initial cardiovascular events in apparently healthy, asymptomatic individuals based upon the assessment of multiple variables, although not in patients with diabetes [76]. (See "Cardiovascular disease risk assessment for primary prevention: Risk calculators".)

The UK Prospective Diabetes Study (UKPDS) risk engine was based on 4540 patients with type 2 diabetes followed for the first four years [77]. Age, sex, duration of diabetes, smoking, systolic blood pressure, total cholesterol, high-density lipoprotein, ethnicity, and hemoglobin A1c level were the variables included in the model (table 2). Patients categorized as low risk are predicted to have a <14 percent 10-year risk of nonfatal or fatal CHD, those categorized as intermediate risk have a 15 to 30 percent risk, and those categorized as high risk a >30 percent 10-year risk. Importantly, a validation cohort was not included in this study.

In type 1 diabetes, two risk engines have been described [78,79]. The first one concerns the Swedish National Diabetes Registry (NDR) [78]. This risk engine was derived from 3661 patients with type 1 diabetes (>90 percent without history of cardiovascular disease [CVD] events). During a follow-up of five years, 197 (non)fatal atherosclerotic CVD events were recorded. Using eight variables (table 2), the predicted five-year risk was 5.4±7.9 percent (C-statistic 0.83). The second is the Steno Risk Engine derived from 4306 patients without a history of CVD events, and it was developed for primary prevention [79]. During a follow-up of 6.8 years, 793 (18.4 percent) patients experienced an atherosclerotic CVD event. Twelve variables were included (table 2), and the C-statistic was 0.826. Importantly, both risk engines included a validation cohort.

RECOMMENDATIONS OF PROFESSIONAL SOCIETIES — In the 2022 Standards of Medical Care in Diabetes, the American Diabetes Association does not recommend routine screening for coronary heart disease (CHD) in asymptomatic patients with diabetes, as outcomes are not improved as long as cardiovascular risk factors are treated [80]. However, in the 2019 European Society of Cardiology Guidelines on diabetes, pre-diabetes, and cardiovascular disease (CVD), the writing group concludes that in asymptomatic patients routine screening is controversial and still under debate [76]. In addition, the guidelines highlight the need for better definition of the characteristics of the patients who should be screened for CHD, stating that screening for silent CHD may be considered in selected high-risk patients with diabetes, such as patients with peripheral artery disease or high coronary artery calcium (CAC) score or with proteinuria.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Assessment of cardiovascular risk".)

SUMMARY

Diabetes mellitus is associated with a twofold increased risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD) mortality. In addition to the increase in cardiovascular events, patients with type 2 diabetes also have a high rate of asymptomatic CHD compared with the general population, which raises the possibility that there might be value from screening for CHD among asymptomatic patients with diabetes. (See 'Introduction' above.)

Whether the patient suffers from type 1 or type 2 diabetes, along with the patient's age and duration of time living with diabetes, will impact the risk for developing CVD. (See 'Epidemiology' above.)

As with screening for any condition, the primary purpose of screening for CHD in patients with diabetes would be to identify patients whose prognosis could be improved with an intervention (ie, medical therapy for risk factors or coronary revascularization). In nearly all patients with diabetes, the results of screening will generally not change medical therapy, since aggressive preventive measures, such as control of blood pressure and lipids, would already be indicated. However, the use of low-dose aspirin may not be warranted in all asymptomatic diabetic patients, since >30 percent of asymptomatic diabetic patients may not have CHD and the use of coronary artery calcium (CAC) score could be considered as a measure to detect/exclude CHD. (See 'Screening issues' above and 'Computed tomography' above.)

In unselected asymptomatic diabetic patients (either type 1 or type 2) who are being treated with appropriate risk factor reduction, screening for CHD has not been shown to improve clinical outcomes. As such, we do not routinely screen for CHD in asymptomatic diabetic patients. High-risk subgroups who might benefit from screening (and revascularization) to improve outcome have not been defined in clinical trials. The real benefit of screening may be in the detection of high-risk CVD (where there is a need for revascularization), and the sequential use of CAC score followed by radionuclide myocardial perfusion imaging (rMPI) for screening may be considered in future trials. (See 'Does screening for subclinical CHD improve outcomes?' above and "Overview of general medical care in nonpregnant adults with diabetes mellitus" and "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease".)

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Topic 1551 Version 29.0

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