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  Diabetes mellitus (DM) is associated with approximately a 2–4 times higher risk of coronary artery disease (CAD), stroke, peripheral artery disease (PAD), and heart failure. These conditions are leading causes of death among people with diabetes, especially in those with coexisting atherosclerotic cardiovascular disease (ASCVD).

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  Subclinical markers including coronary artery calcium (CAC) and carotid intimal medial thickness (IMT) are prevalent in people with diabetes and predict future cardiovascular events. CAC scoring is especially valuable in identifying high risk but asymptomatic individuals with diabetes.

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  Mortality and event rates from CAD, CVD, and all causes increase progressively across disease states, from metabolic syndrome to diabetes without CVD, to CVD alone, and are highest in those with both diabetes and CVD .

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  While previous studies classified diabetes as a “coronary heart disease risk equivalent,” recent evidence shows heterogeneity in cardiovascular risk among people with diabetes. Factors like duration of diabetes, HbA1c, and kidney function strongly influence whether an individual reaches this equivalence.

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  People with diabetes often exhibit coexisting hypertension, dyslipidemia, obesity , and unhealthy lifestyle habits , amplifying their ASCVD risk. However, risk factor control is generally suboptimal , with less than 20% achieving combined targets for HbA _1c , BP, and LDL-C.

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  Several tools like UKPDS, TIMI, and SCORE2-Diabetes offer tailored risk prediction for individuals with diabetes. Newer models integrate diabetes-specific factors such as duration, HbA _1c , and eGFR to improve accuracy.

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  Achieving control of multiple risk factors significantly reduces cardiovascular event rates. Clinical trials like Steno-2 demonstrate that intensive therapy targeting glucose, BP, and lipids can reduce cardiovascular morbidity and mortality in people with type 2 diabetes.

Diabetes mellitus (DM) is characterized by hyperglycemia as a result of insulin secretion, excessive glucagon secretion, or insulin resistance. Globally, DM prevalence was estimated to be 9.3% (463 million people) in 2019, predicted to increase to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045. Overall, 38.4 million persons (11.6%) in the United States of all ages had DM in 2021, including 38.1 million adults > 18 years of age (14.7%), with an additional 97.6 million (38.0%) having pre-DM.

Atherosclerotic cardiovascular diseases (ASCVD), i.e., coronary artery disease (CAD), cerebrovascular disease, and peripheral artery disease (PAD), are the most important complications in those with DM, representing the main causes of morbidity and mortality in subjects with type 2 DM, where it occurs approximately 15 years earlier than in people without DM and affecting about one-third of patients with type 2 DM. The risk for developing ASCVD is two to four times higher in patients with versus without DM. Half or more of medical costs of DM in the United States are attributed to treating cardiovascular complications.

Atherosclerosis is accelerated in type 2 DM and involves progression from the fatty streak to the formation of more complex atherosclerotic plaques that can rupture, resulting in myocardial infarction (MI), unstable angina, or strokes. Patients with DM who have microvascular complications are also at higher risk of accelerated atherosclerosis, ultimately resulting in cerebrovascular and cardiovascular events and premature mortality.

This chapter describes the epidemiology of ASCVD in persons with DM, including major complications, ASCVD risk assessment, as well as the major cardiovascular disease risk factors in those with DM and the current state of their control and relation to cardiovascular outcomes.

ASCVD are the leading causes of death in persons with DM. Multiple indirect or direct pathways resulting in accelerated atherosclerosis have been proposed to explain the deleterious effects of hyperglycemia on the cardiovascular system. Indirect pathways promoted by hyperglycemia include worsening of dyslipidemia, especially the development of atherogenic dyslipidemia and sympathetic nervous system dysfunction. Direct acceleration of the atherosclerotic process by hyperglycemia may be in part related to endothelial dysfunction that in turn promotes vasoconstrictive, proinflammatory, and prothrombotic processes that contribute to plaque development and rupture. Among several large studies of persons with established CAD, 18% to 31% already have DM and more than a third have pre-DM. From the Ludwigshafen Risk and Cardiovascular Health Study, approximately 20% of males and 25% of females had previously diagnosed DM. Among the Euro Heart Survey on Diabetes and the Heart of more than 4000 patients referred to a cardiologist because of suspected CAD, 31% had manifest DM. And in another study from Spain, among 662 consecutive patients admitted to the hospital without a previous diagnosis of DM who were referred for coronary intervention, the prevalence of DM was 45%.

Prior to the development of clinical events, subclinical atherosclerosis is normally present and identifies those at greater risk for the development of clinical events. Most data on subclinical atherosclerosis derives from carotid ultrasonography measuring carotid intimal medial thickness and plaque for examining carotid atherosclerosis, coronary artery calcium (CAC) scanning for examining coronary atherosclerosis, and ankle-brachial index (ABI) screening for evaluation of peripheral arterial disease. In the Cardiovascular Health Study (CHS), 1343 patients with DM, 1432 patients with impaired glucose tolerance (IGT), and 2421 normoglycemic patients were followed on average for 6.4 years. Those with DM had a higher prevalence of clinical and subclinical cardiovascular disease (CVD) (assessed by several measures) that was strongly associated with subsequent coronary heart disease (CHD), stroke, and heart failure ( Fig. 6.1 ).

Diabetes status and presence of subclinical and clinical CVD at baseline and incidence of specific events among males and females in the CHS. CHD , Coronary heart disease; CVD , cardiovascular disease; DM , diabetes mellitus; IGT , impaired glucose tolerance.

Modified from Kuller LH, Velentgas P, Barzilay J, et al. Diabetes mellitus: subclinical cardiovascular disease and risk of incident cardiovascular disease and all-cause mortality, Arterioscler Thromb Vasc Biol . 2000;20:823–829.

In a systematic review of the relevance of carotid IMT in patients with type 2 DM and IGT comprising 23 studies with 20,111 patients, including 4019 with DM and 1110 with IGT, showed those with DM to have increases in IMT approximately three times that of those with IGT, as well as an increased risk of MI and stroke in those with DM of nearly 40%. Moreover, the Bruneck study examined patients with metabolic syndrome who had an increased 5-year incidence and progression of carotid atherosclerosis as well as clinical events compared with controls.

Both low (<0.9) and high (>1.3) ABI as a measure of PAD has been associated with increased cardiovascular and other complications in persons with type 2 DM among a large cohort study of 34,689 persons, with increases in incidence (per 1000 person-years) for mortality and acute MI of 15.4 and 4.1, respectively, with risks rising steeply below 0.9. A cohort study from China also recently showed low ABI (<0.9) as well as ankle-brachial pulse wave velocity (highest quartile) to be independently associated with cardiovascular and total mortality, with the combination of the two being associated with the highest risks (relative risks of 4.5 for all-cause and 9.7 for cardiovascular mortality). Finally, a Brazilian study of persons with type 2 DM showed after 10 years of follow-up, those with a baseline ABI of ≤0.90 have a 2.1-fold increased risk of all-cause mortality, 2.7-fold excess risk of cardiovascular mortality, and a 2.5-fold increased risk of major adverse cardiovascular events.

Several studies have also assessed the prevalence and progression of CAC and its prognostic significance for ASCVD events in persons with DM. Wong et al. reported in a study of 1823 individuals aged 23 to 79 years that the prevalence of CAC increased progressively across metabolic risk groups: among men, CAC prevalence was 53.5% in those without metabolic syndrome or diabetes, 58.8% in those with metabolic syndrome, and 75.3% in those with diabetes; among women, the corresponding prevalences were 37.6%, 50.8%, and 52.6%, respectively. CAC prevalence also rose with the number of metabolic syndrome components, increasing from 34% in those with none to 58% in those with all five components. Moreover, data from the Multi-Ethnic Study of Atherosclerosis (MESA) showed a greater prevalence of CAC in those with metabolic syndrome and especially DM, with an approximate 10-fold increase in CHD events across CAC scores ranging from 0 to > 400; annual CHD event rates in those with DM ranged from 0.4% per year in those with CAC scores of 0% to 4% per year with CAC scores of > 400 ( Fig. 6.2 ), with CAC providing significant improvements in the C-statistic beyond risk factors. In a follow-up study from MESA, those with metabolic syndrome or DM had a higher incidence and absolute progression of CAC compared with patients without DM. In addition, CAC progression predicted future CHD events ( Fig. 6.3 ). Moreover, data from the Dallas Heart Study showed that both MetS and DM were independently associated with a greater prevalence of atherosclerosis evaluated by CAC, with the highest prevalence seen in those fulfilling both criteria. Elkeles et al. prospectively evaluated CAC score as a predictor for CVD events in 589 patients with type 2 DM, finding that after 4 years first CHD and stroke events were 32% greater for every doubling of CAC score. CAC scoring improved discrimination over and above the Framingham CHD risk score and the United Kingdom Prospective Diabetes Study (UKPDS) risk score. Finally, in a recent meta-analysis of 10 studies ( n = 110,396 person-years) with prognostic data, the pooled relative risks for the incidence of all-cause death and/or cardiovascular events were 4.03 (95% CI, 3.04–5.34), 5.87 (95% CI, 4.32–7.99), and 9.04 (95% CI, 5.81–14.06), respectively, for CAC scores >0 versus 0, CAC scores ≥100 versus 0. These data support the important role of CAC scoring as the most valuable subclinical disease measure to improve risk prediction in asymptomatic patients with DM.

Annual CHD event rates (%) by calcium score categories in subjects with diabetes, metabolic syndrome ( MetS ), or neither condition. CHD , Cardiovascular Health Study; DM , diabetes mellitus.

Adapted from Malik S, Budoff MJ, Katz R, et al. Impact of subclinical atherosclerosis on cardiovascular disease events in individuals with metabolic syndrome and diabetes: the multi-ethnic study of atherosclerosis. Diabetes Care . 2011;34(10):2285–2290.

A , Incidence of CAC (per 100 person-years) according to metabolic syndrome ( MetS ) and diabetes ( DM ) status by gender among persons without baseline CAC. B , Progression of CAC (mean unadjusted absolute change in volume score) according to MetS and DM status by gender in persons without baseline CAC. C , CHD event rates (per 1000 person-years) according to tertile of CAC progression by presence of MetS and DM. Data are not shown for persons with DM without MetS because of an insufficient number of CHD events. CHD , Cardiovascular Health Study; CAD , coronary artery disease; DM , diabetes mellitus.

From Wong ND, Nelson JC, Granston T, et al. Metabolic syndrome, diabetes, and incidence and progression of coronary calcium: the Multiethnic Study of Atherosclerosis study. JACC Cardiovasc Imaging. 2012;5:358–366.

Using data from the US National Health and Nutrition Examination Survey (NHANES), we initially demonstrated a stepwise increase in mortality rates from coronary artery disease (CAD), cardiovascular disease (CVD), and all causes across progressively more severe disease states: from metabolic syndrome, to diabetes without prior CVD, to CVD without diabetes, with the highest mortality observed in individuals with both prior CVD and diabetes ( Fig. 6.4 ). In addition, the CALIBER UK cohort showed the most common initial manifestations of CVD to be PAD and heart failure, followed by MI and stroke; this emphasizes the importance of early identification and screening of these conditions ( Fig. 6.5 ). A meta-analysis involving nearly 700,000 patients and over 50,000 vascular outcomes from the Emerging Risk Factors Collaboration ( Fig. 6.6 ) showed DM to be associated with a two- to threefold excess risk for a wide range of vascular diseases independently from conventional risk factors, including MI, coronary death, hemorrhagic stroke, and other vascular deaths. From the UK Clinical Practice Research Datalink of over 700,000 adults with and without type 2 DM with follow-up for first CVD events over 11 years, while type 2 DM was associated with a small increase in CVD events (HR, 1.06 [1.02–1.09]) in White individuals, there was a greater increase in risk seen in individuals of South Asian ethnicity (1.28 [1.09–1.51]), primarily due to an increased risk of MI (1.53 [1.08–2.18]). In a systematic review and meta-analysis from 26 observational studies among over 1.3 million persons across 30 countries, the age at DM diagnosis was inversely associated with all-cause mortality and macrovascular and microvascular disease risk (all P < 0.001). Each 1-year increase in age at DM diagnosis was associated with a 4%, 3%, and 5% decreased risk of all-cause mortality, macrovascular disease, and microvascular disease, respectively, adjusted for age.

Metabolic syndrome and diabetes in relation to CHD, CVD, and total mortality: US mention and female ages 30–74 (risk factor-adjusted Cox regression): NHANES II follow-up ( n = 6255). CHD , Cardiovascular Health Study; CVD , Cardiovascular disease; MetS , metabolic syndrome.

Adapted from Malik S, Wong ND, Franklin SS, Kamath TV, L’Italien GJ, Pio JR, Williams GR. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation . 2004;110(10):1245–50.

CALIBER UK cohort ( n = 1.9 million) most common initial presentations of cardiovascular disease ( CVD ) in diabetes mellitus ( DM ).

Adapted from Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1.9 million people. Lancet Diabetes Endocrinol . 2015;3(2):105–113.

Hazard ratios ( HRs ) for vascular outcomes in people with versus those without diabetes at baseline. CI , Confidence interval; I , statistic for heterogeneity.

From Emerging Risk Factors Collaboration; Sarwar N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010;375:2215–2222.

There is also a wealth of data regarding long-term glycemic control in patients with DM and its association with macrovascular complications such as MI, stroke, amputation, and total mortality. In the UKPDS 35 each 1% reduction in mean hemoglobin A1c (HbA _1c ) was associated with reductions in risk of 21% for any endpoint related to DM, 21% for deaths, and 40% for MI. The European Prospective Investigation into Cancer and Nutrition (EPIC) study comprising 4662 males aged 45 to 79 years showed those with manifest DM had a 3.5-fold increased risk of death from all causes, more than an 8-fold increased risk of cardiovascular mortality, and a 10-fold increased risk for CHD compared with patients with an HbA _1c of less than 5%. However, from an HbA _1c from below 5% to above 7%, there was a gradual increase for all of the above-mentioned endpoints, suggesting that even in the normal upper range of HbA _1c an increased risk of death or nonfatal coronary complications was present.

Significant data also support DM as a stronger risk factor for CVD outcomes in females compared to males. A 36-year follow-up in the Framingham Heart Study initially showed DM to be associated with a 3.7-fold greater risk of all CVD events in females compared to 2.2-fold in men. There was a 6.4-fold greater risk of PAD in females with DM compared to 3.4-fold in men with DM; for heart failure these risks were 7.8-fold and 4.4-fold, respectively. Moreover, the Interheart Study showed DM to be a stronger risk factor for CVD in females than in men. The British Regional Heart Study and British Women’s Heart Health Study examined a large panel of traditional and more novel risk markers, such as insulin resistance, inflammation, activated coagulation, and endothelial dysfunction, in 7529 men and females aged 60 to 79 years with no previous MI showed greater differences in several of these factors among females compared to men with DM versus without DM, potentially explaining their greater CVD risk. There also was an increased risk of death in females with DM who developed complications after MI, such as congestive heart failure. However, in the TECOS trial of adults with type 2 DM and ASCVD, females with DM had a lower risk of secondary MI (HR, 0.70 [95% CI, 0.55–0.90]) and stroke (HR, 0.52 [95% CI, 0.38–0.71]) than males with DM. In the UK Biobank, the association between previously diagnosed DM and MI was stronger in females (HR, 2.33 [95% CI, 1.96–2.78]) than in males (HR, 1.81 [95% CI, 1.63–2.02]). Among male National Health Interview Study participants enrolled in 2000 to 2009 and followed up through 2011, DM was associated with increased risk for heart disease mortality (HR, 1.72 [95% CI, 1.53–1.93]), cerebrovascular mortality (HR, 1.48 [95% CI, 1.18–1.85]), and CVD mortality (HR, 1.67 [95% CI, 1.51–1.86]). Among female participants, DM was also associated with increased risk for heart disease mortality (HR, 2.02 [95% CI, 1.81–2.25]), cerebrovascular mortality (HR, 1.43 [95% CI, 1.15–1.77]), and CVD mortality (HR, 1.85 [95% CI, 1.69–1.96]).

In a study by Haffner et al. had found that among a Finnish male population, DM alone carried the equivalent risk of future MI and fatal CVD as patients without DM but a previous MI ( Fig. 6.7 ). But more recently a meta-analysis of nearly 40,000 patients with a follow-up of up to 25 years showed the risk of CAD events to be over 40% lower in those with DM but no prior MI compared to patients with a prior MI but no DM ( Fig. 6.8 ). More recent differences in the DM definition and the extent of comorbidities in the different studies may explain these differences. In the Finnish study, DM diagnosis was based on higher glucose cutpoints used in the past. However, more recent studies using more rigorous definitions of MI and lower thresholds of glucose for defining DM have shown lower risk in patients with DM but without CVD compared with patients after MI but without DM. Evans et al. showed among 3402 patients with newly diagnosed type 2 DM and 5350 post-MI patients, the post-MI group had a nearly threefold greater risk of death and threefold greater risk of recurrent MI over follow-up of more than 10 years. Also, the ARIC study showed those with a history of MI without DM had a 1.9-times greater risk of fatal and nonfatal MI and a 1.8-times greater risk of CHD mortality compared to those with DM without a history of MI, although a similar risk of stroke. Wannamethee et al. showed that patients with both early and late onset of DM had a significantly greater risk of major CHD and CVD events and all-cause mortality compared to those without DM or prior MI, but those diagnosed before age 60 who had a duration of DM of more than 30 years had a similar risk as those with a prior MI without DM. More recent data from Rana et al. from Kaiser Permanente Northern California corroborate these results, showing persons with DM with 10 years or longer duration have a similar risk of future CHD events compared to those with a prior MI. Imaging studies have also shown patients with a DM duration of 10 years or longer showed a greater plaque burden in most diseased segments; also, the proportion of intravascular ultrasound (IVUS)-defined thin-cap fibroatheroma in those with long-standing DM was greater than in those with a DM duration of less than 10 years. Finally, in a recent pooling of four US cohorts Atherosclerosis Risk in Communities [ARIC], Jackson Heart Study [JHS], Multi-Ethnic Study of Atherosclerosis [MESA], Framingham Heart Study-Offspring [FHS-OS]) comprising over 27,000 adults, classifying persons according to the presence or absence of DM and CVD, DM was identified to be a cardiovascular disease risk equivalent in only one-fifth of CVD-free adults. High HbA _1c , long DM duration, and DM medication use were the most important predictors of CVD risk equivalence. DM is a CVD risk equivalent for women, white people, those of younger age, with higher triglycerides or CRP, or reduced kidney function.

Incidence of cardiovascular events during a 7-year follow-up in relation to history of MI in patients with type 2 diabetes and in nondiabetic patients. CHD , Coronary heart disease; DM , diabetes mellitus; MI , myocardial infarction.

Data from Haffner SM, Lehto S, Rönnemaa T, et al. Mortality from coronary heart disease in patients with type 2 diabetes and in nondiabetic patients with and without prior myocardial infarction. N Engl J Med. 1998;339:229–234.

Odds of coronary heart disease according to presence of diabetes or myocardial infarction alone: meta-analysis of 38,578 subjects. CI , Confidence interval; MI , myocardial infarction.

From Bulugahapitiya U, Siyambalapitiya S, Sithole J, Idris I. Is diabetes a coronary risk equivalent? Systematic review and meta-analysis. Diabet Med . 2009;26(2):142–148.

DM is associated with great heterogeneity in risk of CVD and many persons with DM are no longer considered CHD risk equivalents. Persons with DM have a wide heterogeneity of risk of CVD based on Framingham risk scores, with approximately half of women and a third of men with DM being without known CVD or with 10-year risk <20%, the cutpoint generally considered to be a CVD risk equivalent. This emphasizes the importance of risk stratification in persons with DM. Assessment of CVD risk is the first step for guiding the intensity of preventive treatments for CVD in persons with DM (see also Chapter 8 ).

The American College of Cardiology/American Heart Association (ACC/AHA) ASCVD risk estimator can be used to estimate the 10-year risk and lifetime risk of a first ASCVD event both in those with DM and without DM. Since the calculator includes DM as a binary risk factor, it does not account for DM-specific risk factors such as duration or HbA _1c levels. Although some variability in calibration exists in various subgroups by gender and race, the precision of risk prediction is similar in those with or without DM. The US 2018 cholesterol management recommendations call for the use of the pooled cohort risk score in all persons with DM aged 40 to 79 years. While statin therapy is recommended for all with type 2 DM, those at higher risk (multiple risk factors or ≥20% 10-year risk) can be considered for a high-intensity statin and ezetimibe as needed to reduce low-density lipoprotein cholesterol (LDL-C) by at least 50%. Moreover, risk-enhancing factors can be further used to inform the treatment decision and include: (1) long duration (≥10 years for type 2 DM or ≥20 years for type 1 DM), (2) albuminuria defined as urine albumin-to-creatinine ratio (UACR) of 30 mg/g, (3) estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m ² , (4) retinopathy, (5) neuropathy, and (6) ABI <0.9, particularly for those younger than age 40 where statin therapy can be considered on the basis of one or more of these risk enhancers. Most recently, Zhao et al. developed a US Pooled Cohort Diabetes Mellitus Risk Score (DMRS) from four major US population-based cohorts comprising 2174 adults with DM followed up to 10 years. Age, sex, HbA _1c , creatinine, systolic blood pressure, DM medication, and smoking were the most important predictors. The DMRS had good internal discrimination and calibration and was externally validated in two other cohorts where it outperformed current risk scores ( Fig. 6.9 ) .

US Pooled Cohort Cardiovascular Disease Risk Scores for Adults with Diabetes Mellitus. From Zhao Y, D’Agostino RB Sr, Malik S, et al. United States Cardiovascular Disease Risk Scores in adults with diabetes mellitus. JACC Adv, 2004;4(1):101–448.

Several other risk prediction algorithms for type 2 DM have been developed. From a recent systematic review of 15 observational studies reporting on seven risk models with >1 validation cohort, the Risk Equations for Complications of Type 2 Diabetes had the best calibration in primary studies with the greatest discrimination measures for all-cause mortality (C-statistics, 0.75 [95% CI, 0.70–0.80]; high certainty), cardiovascular mortality (0.79 [95% CI, 0.75–0.84]; low certainty), end-stage kidney disease (ESKD) (0.73 [95% CI, 0.52–0.94]; low certainty), MI (0.72 [95% CI, 0.69–0.74]; moderate certainty), and stroke (0.71 [95% CI, 0.68–0.74]; moderate certainty). The updated version of the QDiabetes risk prediction algorithm had C statistics between 0.81 and 0.89. Risk prediction algorithms for CVD among individuals with DM have also been developed. A meta-analysis found an overall pooled C statistic of 0.67 for 15 algorithms developed in populations with DM and 0.64 for 11 algorithms originally developed in a general population. The Thrombolysis In Myocardial Infarction (TIMI) risk score for CVD events performed moderately well among adults with type 2 DM and high CVD risk. The C statistic was 0.71 (95% CI, 0.69–0.73) for CVD death and 0.66 (95% CI, 0.64–0.67) for a composite endpoint of CVD death, MI, or stroke. The UK Prospective Diabetes Study (UKPDS) risk score ( Fig. 6.10 ) developed for persons with type 2 DM includes, along with major ASCVD risk factors, duration of DM, HbA _1c levels, and atrial fibrillation for determining the 10-year risk of fatal or nonfatal CAD or stroke. The MESA-HNR CAD risk estimator for patients with type 2 DM is based on patients from the MESA and Heinz Nixdorf Recall (HNR) studies and includes both conventional and novel clinical risk factors, as well as CAC and shows improved discrimination for incident CAD over several other risk scores.

UKPDS risk engine for diabetes. From Stevens RJ, Kothari V, Adler AI, Stratton IM; United Kingdom Prospective Diabetes Study ( UKPDS ) Group. The UKPDS risk engine: a model for the risk of coronary heart disease in type II diabetes (UKPDS 56).

The European Society of Cardiology guideline for DM patients has recently recommended the use of newly developed SCORE2-Diabetes algorithm ( Fig. 6.11 ) to assess the 10-year CVD risk in individuals aged 40 years and older who have T2DM without ASCVD or severe target-organ damage. SCORE2-Diabetes incorporates traditional CVD risk factors such as age, smoking status, systolic blood pressure, and total and high-density lipoprotein cholesterol along with diabetes-specific factors including age at diabetes diagnosis, HbA _1c , and eGFR. Risk categories defined by the guideline include <5% for low risk, 5% to <10% for moderate risk, 10% to <20% for high risk, and ≥20% for very high risk. These risk thresholds aim to facilitate shared decision-making discussions between physicians and patients, guiding the selection of appropriate treatment intensity and additional interventions to prevent ASCVD.

Individual and Composite Cardiovascular Disease Risk Factor Control in US Adults with Diabetes. Adapted from Fan W, Song Y, Inzucchi SE, et al. Composite cardiovascular risk factor target achievement and its predictors in US adults with diabetes: The Diabetes Collaborative Registry. Diabetes Obes Metab . 2019;21(5):1121–1127.

While meta-analyses from current data do not support screening for CAD in patients with type 2 DM for preventing fatal events, recent European guidelines, note for risk stratification that screening of CAD with computed tomography coronary angiography or functional imaging such as radionuclide myocardial perfusion imaging, stress cardiac magnetic resonance imaging, or exercise or pharmacological stress echocardiography may be considered among patients in whom CAD cannot be excluded by clinical assessment alone. Additionally, the CAC score may be considered as a risk modifier in CVD risk assessment of asymptomatic patients at moderate risk. US guidelines also indicate CAC as an option for further refinement of risk for determining the appropriateness of statin therapy after consideration of global risk assessment and risk-enhancing factors, although not specifically in those with DM, and in fact, for those with DM, statin therapy should not be withheld or delayed in those with a CAC score of 0. Prior investigations show CAC to be a very effective risk stratifier in those with DM and those with high CAC scores and long duration of DM, in particular, identifies persons with substantial ASCVD risk over 10 years of follow-up. Earlier AHA recommendations also noted the appropriateness of CAC scoring to stratify risk of persons with DM at intermediate risk aged 40 years or greater.

Multiple cardiovascular risk factors are commonly seen in those with DM. NHANES has shown 21% of adults with type 2 DM had hypertension, hyperlipidemia, and obesity together, with another 36% having two of these risk factors. We review here the most common risk factors that cluster in those with DM: obesity, dyslipidemia, hypertension, and lifestyle factors and their impact on cardiovascular disease risk.

A variety of lifestyle factors (higher alcohol consumption, lower physical activity [PA], higher sedentary time, and unhealthy diet) has also been shown to be associated with DM risk in adults over a median 3.8 years of follow-up and may thus further affect cardiovascular disease risk (see also Ch. 3 , Ch. 17 ). Those with the least favorable lifestyle profile had an increased risk for DM compared with those with the most favorable lifestyle profile. A meta-analysis of 14 studies also showed those with the most favorable combined lifestyle factors had a lower DM risk compared to those with the least favorable combined lifestyle factors. Sedentary behavior, including television viewing, has also been shown to be associated with DM risk in a systematic review and meta-analysis. Among a meta-analysis of 39 cohort studies, sugar-sweetened and artificially sweetened beverage intake show an association with increased type 2 DM risk. In a systematic review and meta-analysis of five eligible prospective studies of 22,591 subjects with DM followed for an average of 9.8 years showed reduced cardiovascular outcomes from replacement analyses of saturated fat with polyunsaturated fat (RR for 2% energy replacement, 0.87 [95% CI, 0.77–0.99]) or carbohydrate (RR for 5% energy replacement, 0.82 [95% CI, 0.67–1.00]).

Despite modest improvements in cardiovascular risk factor control over years among those with DM, many are insufficiently controlled for multiple risk factors needed to achieve meaningful reductions in CVD risk. We showed from the Diabetes Collaborative Registry individual target attainment for HbA _1c , BP, LDL-C, and nonsmoking status to be 73.6%, 69.0% (40.3% for BP <130/80 mm Hg), 48.6%, and 85.2%, respectively. However, only 21.6% (13.0% with BP <130/80 mm Hg) were at target for all four measures ( Fig. 6.12 ), with multiple target attainment higher in men (23.6%) versus women (18.6%) and in white people (22.5%) versus African-American people (14.7%) and people of other races (20.8%; P < 0.01). Moreover, recent data from the NHANES indicated that among adults with type 2 DM, approximately half met individual targets for HbA _1c (55.8%), blood pressure (51.3%), and LDL cholesterol (49.3%), while a higher proportion were nonsmokers (84.3%). However, only 17.3% achieved combined control of HbA _1c , blood pressure, and LDL cholesterol, and this dropped to 16.0% when nonsmoking was included, and to under 10% when BMI targets were also considered. These data demonstrate the need to reduce clinical inertia among healthcare providers to ensure the composite of these risk factors is addressed with appropriate lifestyle interventions and pharmacologic therapies.

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