cardiovascular (CV) risk and diabetes

Last edited 12/2020 and last reviewed 06/2021

Coronary heart disease (CHD) risk:

• incidence of CHD events including silent myocardial infarction is increased 2-3 fold in comparison with non-diabetics - the relative risk being higher in women (1)
• there is evidence from a large prospective study, that CHD risk in people with diabetes, but without overt CHD was similar to than in non-diabetics with established CHD (2)
• in consideration of more recent data regarding the use of statin treatment in Heart Protection Study (HPS), CARDS,and the lipid-lowering arms of ALLHAT (ALLHAT-LLT) and ASCOT (ASCOTLLA) (see linked items)
  • HPS included 5,963 people with diabetes (90% type 2), 29% of the total patient population of 20,536. Almost half of these 5,963 patients had no history of CVD, and the mean TC and LDL-C levels at baseline were 5.8mmol/l and 3.3mmol/l, respectively
    • this study showed the benefits of statin treatment in people with diabetes
      • over a median duration of 4.8 years - major coronary events were reduced significantly from 12.6% in the placebo group to 9.4% in the simvastatin 40mg group (NNT 32). There were also reductions in CHD death (NNT 67), non-fatal MI (NNT 50), major cardiovascular events (NNT 21), stroke (NNT 67) and revascularisation (NNT 59)
      • subgroup analysis showed that statin treatment was beneficial in all diabetic patients - this benefit was evident whether or not they already had manifest CVD or high cholesterol levels
  • CARDS - this study also supports statin use for primary prevention in people with diabetes
    • trial included 2,838 patients with type 2 diabetes and at least one other cardiovascular risk factor, but no history of CVD
      • over a median follow-up of 3.9 years - there were significant reductions in major cardiovascular events (from 9.0% with placebo to 5.8% with atorvastatin 10mg NNT 32)). There were also reductions in acute coronary events (NNT 53) and stroke (NNT 77)
      • the NNT to prevent a major cardiovascular event over 3.9 years in people with diabetes and TC >5.4mmol/l was 26; the corresponding NNT for patients with TC <= 5.4mmol/l was 42
  • ALLHAT-LLT and ASCOT-LLA, both of which contained large numbers of patients with diabetes, provided less evidence to support statin use in this patient group (3)
    • 10,305 patients were included in ASCOT-LLA with hypertension and at least three other cardiovascular risk factors - 2,532 (25%) had diabetes
      • in the total study population, atorvastatin 10mg for a median of 3.3 years significantly reduced CHD death and non-fatal MI compared with placebo from 3.0% to 1.9% - however the NNT was 91, suggesting only a modest clinical effect
        • subgroup of patients with diabetes, results were disappointing, with no significant reduction in coronary events

Is diabetes a coronary disease equivalent?

• a study by Bulugahapitiya et al (3) evaluated 14 cohorts in a systematic review and meta-analysis and found that patients with diabetes and no history of MI had a lower risk of coronary artery disease events than patients without diabetes and a history of MI
  • the duration of follow-up was 5-25 years (mean 13.4 years) and the age range was 25-84 years. Patients with diabetes without prior myocardial infarction have a 43% lower risk of developing total CHD events compared with patients without diabetes with previous myocardial infarction (summary odds ratio 0.56, 95% confidence interval 0.53-0.60).
  • the discrepancies between this meta-analysis and the Haffner study (2) can be explained by the fact that diabetes, as a cardiovascular process, is complex
    • the cardiovascular prognosis for type 2 diabetes depends on several variables, including age, duration of diabetes, degree of optomisation of serum lipid concentrations and blood pressure, and presence of other comorbid conditions such as nephropathy (microalbuminuria is associated with increased cardiovascular risk)

In overall consideration of these trial results then they "....support statin use in people with type 2 diabetes. However, it is still unclear whether statin use in all patients with type 2 diabetes is supported regardless of their cholesterol levels, or whether all people with diabetes are at great enough absolute risk of a cardiovascular event to benefit from treatment...(4)"

Patients with diabetes who suffer a myocardial infarction have a higher initial case fatality and a worse prognosis during the first and subsequent years post infarction. There was initial evidence that, in the acute phase insulin/glucose infusion, followed by at least 3 months subcutaneous insulin has been shown to improve survival in the swedish DIGAMI study (5). However this evidence was not supported by the subsequent study DIAGMI 2 (6).

Coronary artery calcium (CAC) score:

• evidence suggests that addition of CAC score to global risk assessment was associated with significantly improved risk classification in those with metabolic syndrome and diabetes, even if diabetes duration was longer than a decade, suggesting a role for the CAC score in risk assessment in such patients (7)

Diabetes dyslipidaemia:

• in primary prevention trial with high prevalence of diabetes and obesity in high CV risk participants, triglycerides and remnant-C (total cholesterol - (LDL-c +HDL-c), but not LDL-c and HDL-c, were associated with MACE. The authors concluded: "Remnant-c should be considered a preferential treatment target in this population" (8)

Reference:

• 1) British Heart Foundation, Factfile 12/2001.
• 2) Haffner SM et al (1998). Mortality from Coronary Heart Disease in subjects with type 2 diabetes and non-diabetic subjects with and without prior myocardial infarction. NEJM; 339:229-34.
• 3) Bulugahapitiya U et al. Is diabetes a coronary risk equivalent? Systematic review and meta-analysis. Diabet Med. 2009 Feb;26(2):142-8
• 4) MeReC Briefing 2004;26:1-8.
• 5)Almbrand B et al (2000). Cost effectiveness of Intense Insulin Treatment after Acute Myocardial Infarction in Patients with Diabetes Mellitus. Results from the DIGAMI study Eur Heart: 21: 733-39.
• 6) Malberg K et al.Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J. 2005 Apr;26(7):650-61
• 7) Malik S et al. Coronary Artery Calcium Score for Long-term Risk Classification in Individuals With Type 2 Diabetes and Metabolic Syndrome From the Multi-Ethnic Study of Atherosclerosis.JAMA Cardiol. 2017 Dec 1;2(12):1332-1340
• 8)
Castañer O, Pintó X, Subirana I, et al. Remnant Cholesterol, Not LDL Cholesterol, Is Associated With Incident Cardiovascular Disease J Am Coll Cardiol. 2020, 76 (23) 2712–2724, doi.org/10.1016/j.jacc.2020.10.008