Blood Pressure
Uncontrolled blood pressure in diabetes is a well-known risk factor for worse cardiovascular outcomes [
7]. Unregulated blood pressure in diabetes accelerates the risk for myocardial infarction, stroke, heart failure, and all-cause mortality.
Optimal blood pressure in patients with diabetes has been a topic of debate over the past several years [
8]. The Joint National Commission (JNC) 8 guidelines of 2013 liberalized the recommendation for patients with diabetes from <130/80 mmHg in the previous guidelines [
9] to <140/90 mmHg [
10]. A systematic review published after JNC 8 concluded that blood pressure–lowering treatment in people with diabetes and systolic blood pressure already <140 mmHg was associated with reduced risk of stroke and albuminuria, and therefore challenged the relaxation of guidelines by JNC 8 [
11]. However, a more recent meta-analysis that included unpublished data in patients with diabetes supported a more liberal blood pressure range up to 140/80 mmHg and concluded that if systolic blood pressure was <140 mmHg, further treatment was associated with increased risk of cardiovascular death [
12]. However, the Systolic Blood Pressure Intervention Trial (SPRINT), which showed benefits of lower blood pressures to 120/80 mmHg in patients with cardiovascular risk factors but excluded all patients with diabetes mellitus [
13], has renewed the controversy regarding the optimum range of blood pressure.
Consistent with JNC 8 [
10], the AHA/ADA guidelines recommend blood pressure of <140/90 mmHg for most individuals with diabetes [
5•], although the optimal blood pressure for individuals with diabetes in conjunction with other cardiovascular risk factors remains controversial.
Lipids
The 2013 ACC/AHA cholesterol guidelines recommend that individuals with diabetes, aged 40–75 years, without clinical ASCVD be on moderate-intensity statin therapy if their baseline LDL-C is 70–189 mg/dL, with consideration of high-intensity statin in those with 10-year ASCVD risk ≥7.5%; high-intensity statin therapy is recommended as first-line therapy in patients aged ≤75 years who have clinical ASCVD [
14]. In the Collaborative Atorvastatin Diabetes Study (CARDS), treatment with atorvastatin 10 mg (moderate intensity) resulted in significant reduction in major cardiovascular events irrespective of pretreatment LDL-C levels [
15]. The 2016 ACC Expert Consensus Decision Pathway on nonstatin therapy identified individuals with diabetes who have concomitant ASCVD risk factors, 10-year ASCVD risk ≥7.5%, chronic kidney disease (CKD), albuminuria, retinopathy, evidence of subclinical atherosclerosis, elevated lipoprotein (a), or elevated high-sensitivity C-reactive protein (hs-CRP) as higher risk and therefore potential candidates for high-intensity statin therapy, with the addition of ezetimibe (or colesevelam) as needed [
16••].
The 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recommend calculating non-HDL-C for risk assessment, especially in patients with hypertriglyceridemia, and defined desirable non-HDL-C in individuals with diabetes or metablic syndrome as <130 mg/dL in high-risk patients and <100 mg/dL in very-high-risk patients [
19]. The International Atherosclerosis Society defined optimal non-HDL-C as <130 mg/dL for primary prevention (particularly in high-risk patients, including those with diabetes with other risk factors) and <100 mg/dL for secondary prevention [
26].
In patients with diabetes, non-HDL-C may remain elevated despite near-normal levels of LDL-C; therefore, non-HDL-C thresholds are included in the 2016 ACC Expert Consensus Decision Pathway on nonstatin therapy, in which non-HDL-C levels ≥130 mg/dL are considered higher risk in patients in diabetes [
16••].
The 2016 European Guidelines on Cardiovascular Disease Prevention found no evidence that apoB was better than LDL-C for ASCVD risk prediction [
20], and in the 2013 ACC/AHA cholesterol guidelines, apoB measurement for assessment of ASCVD risk was considered of uncertain value [
14]. However, for individuals with diabetes or metabolic syndrome, the 2016 ESC/EAS lipid guidelines defined desirable apoB concentration as <100 mg/dL in high-risk patients and <80 mg/dL in very-high-risk patients [
19].
The AHA scientific statement on triglycerides and ASCVD classified fasting triglyceride levels <100 mg/dL as optimal and <150 mg/dL as normal [
37]. In the 2016 ADA guidelines, triglyceride levels ≥150 mg/dL are considered elevated [
38]. The presence of hypertriglyceridemia is a marker for elevated triglyceride-rich lipoproteins, which, because of their atherogenic potential, should be included in ASCVD risk assessment especially in patients with diabetes, who often have increased production and impaired clearance of triglyceride-rich lipoproteins [
39].
The 2016 ADA guidelines define low HDL-C levels as <40 mg/dL in men and <50 mg/dL in women [
38].
Hemoglobin A1c
Glycosylated hemoglobin (HbA1c) reflects the glycemic index of the hemoglobin for the past 8–12 weeks. It is the most commonly used test in diabetes assessment along with fasting glucose. Mounting evidence supports the association of elevated HbA1c, even below the threshold for diagnosis of diabetes, with adverse cardiovascular outcomes after adjustment for traditional cardiovascular risk factors [
45‐
47]. However, as with HDL-C, clinical trials of interventions to improve HbA1c have failed to demonstrate ASCVD benefit with intensive verus standard glycemic control [
48‐
50], and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was stopped early as a result of increased total and cardiovasular mortality in the intensive–glucose lowering group [
48]; the cause for the excess mortality has not been determined [
48]. On the basis of these trials, the ADA, ACC, and AHA issued a joint statement emphasizing an individualized approach to HbA1c evaluation [
51].