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22 August 2016
Atherogenic dyslipidaemia and silent coronary artery disease in type 2 diabetes

Atherogenic dyslipidaemia was independently associated with asymptomatic coronary artery disease in patients with type 2 diabetes and low-density lipoprotein cholesterol (LDL-C) levels <3.35 mmol/L (130 mg/dL).

Valensi P, Avignon A, Sultan A, Chanu B, Nguyen MT, Cosson E. Atherogenic dyslipidemia and risk of silent coronary artery disease in asymptomatic patients with type 2 diabetes: a cross?sectional study. Cardiovasc Diabetol 2016;15:104 .
Summary
Comments & References
STUDY SUMMARY
Objective: To investigate whether atherogenic dyslipidaemia (triglycerides ≥2.26 mmol/L [200 mg/dL) and high-density lipoprotein cholesterol [HDL-C] ≤0.88 mmol/L [34 mg/dL] ), is predictive of risk of silent myocardial ischaemia (SMI) or angiographic coronary artery disease (CAD) in asymptomatic patients with type 2 diabetes.
Study design: Cross-sectional cohort study
Study population: 1,080 asymptomatic patients with type 2 diabetes (mean age 61.6 ± 9.0 years, 57% male, mean diabetes duration 13.8 ± 8.5 years, mean HbA1c 8.5%) with a normal resting electrocardiogram, at least one additional cardiovascular risk factor (dyslipidaemia, hypertension, smoking, nephropathy, family history of premature CAD, or peripheral occlusive arterial disease) and LDL-C levels <3.35 mmol/L (130 mg/dL).
Key outcomes:

·       SMI, defined as evidence of an abnormal ECG stress test and/or abnormal myocardial scintigraphy imaging (i.e., defects in at least 3 out of 17 segmental regions).

·       Angiographic CAD, defined as ≥70 % narrowing of the luminal diameter in the left anterior descending artery, the circumflex artery, a well-developed marginal vessel or the right coronary artery or ≥50 % narrowing of the left main coronary artery diameter.

Methods: Patients with SMI were subsequently screened for angiographic CAD. Multivariate logistic regression analysis based on models including factors associated with silent coronary status with a p value ≤0.10 in univariate analyses was used to investigate the association between the presence of atherogenic dyslipidaemia and SMI or asymptomatic CAD.
Main results:

Overall, atherogenic dyslipidaemia was detected in 60 (5.6%) patients with LDL-C levels <3.35 mmol/L. In the subgroup of 584 patients with LDL-C levels <2.6 mmol/L (100 mg/dL), atherogenic dyslipidaemia was diagnosed in 35 (6.0%).

 SMI was identified in 292 (27%) patients; of these 218 subsequently underwent a coronary angiography. CAD was confirmed in 91 patients (8.4% of the total study population of 1080 patients and 41.7 % of the patients with SMI). In the subgroup of patients with LDL-C levels <2.6 mmol/L, SMI was diagnosed in 155 patients (26.5%) and CAD was confirmed in 45 patients.

 The association of atherogenic dyslipidaemia with SMI and silent CAD is summarised in the Table. In the subgroup of 584 patients with LDL-C levels <2.6 mmol/L, atherogenic dyslipidaemia was also associated with silent CAD (odds ratio 3.6, 95% CI 1.5–9.0).

Table. Association of atherogenic dyslipidaemia with SMI and silent CAD in asymptomatic type 2 diabetes patients with LDL-C <3.35 mmol/L

 

Odds ratio (95% CI)*

p-value

SMI

1.8 (1.0-3.3)

0.05

Silent CAD

4.0 (1.7-9.2)

0.001

* Comparing patients with SMI or CAD with those without

Authors’ conclusion: Atherogenic dyslipidaemia was associated with an increased risk of SMI and silent CAD in patients with type 2 diabetes and LDL-C levels <3.35 mmol/L. Specific management of atherogenic dyslipidaemia might help to reduce the high residual burden of cardiovascular disease.

COMMENT

Silent CAD in individuals with type 2 diabetes has long been a matter of clinical concern, with studies suggesting that about at least 20% of patients may be affected (1).  Even with multifactorial risk factor intervention, including management of LDL-C, the presence of silent CAD is predictive of progression and future cardiac events (2). This scenario makes the case for considering other risk factors in the management plan of type 2 diabetes patients.

 There is evidence highlighting the importance of targeting atherogenic dyslipidaemia, especially elevated triglycerides, in type 2 patients who have well controlled LDL-C levels on statin therapy (3,4). These findings would therefore imply that atherogenic dyslipidaemia may be relevant to preventing progression of silent CAD in this patient group. The relatively low prevalence of atherogenic dyslipidaemia in this study, however, may result from the criteria used by the authors, which were based on tertiles from the ACCORD Lipid study. Instead, using gender-specific cut-offs for HDL-C, as well as the threshold for hypertriglyceridaemia based on the current definition of the metabolic syndrome, -treatment lipid-values would actually yield a much higher prevalence of atherogenic dyslipidaemia in Caucasian patients with type 2 diabetes, by up to 40% (5,6).

 The results of this cross-sectional study lend support to this proposal, showing that this dyslipidaemic profile is significantly associated with both SMI and silent CAD in patients with LDL-C levels less than 3.35 mmol/L (130 mg/dL). Moreover, the association between atherogenic dyslipidaemia and silent CAD persisted in patients with LDL-C levels <2.6 mmol/L (100 mg/dL). Given the high prevalence of silent CAD in these patients (affecting about 20%, even higher in patients with LDL-C levels <1.8 mmol/L or 70 mg/dL), these findings add to the case for managing atherogenic dyslipidaemia to reduce the residual burden of both symptomatic and silent CAD. Indeed, the author makes the point in his conclusions that screening of type 2 diabetes taking account of the presence of atherogenic dyslipidaemia may also help in earlier identification of silent CAD, which may be key to reducing the residual risk of cardiovascular disease in these patients. While larger prospective studies are needed to corroborate these findings, the results of this study highlight the importance of atherogenic dyslipidaemia as a contributor to the lipid-related residual risk of both symptomatic and asymptomatic CAD in type 2 diabetes.

References

1. Wackers FJ, Young LH, Inzucchi SE et al. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care 2004;27:1954-61.

2. Valensi P, Pariès J, Brulport-Cerisier V et al. Predictive value of silent myocardial ischemia for cardiac events in diabetic patients: influence of age in a French multicenter study. Diabetes Care 2005;28:2722-7.

3. Sacks FM, Carey VJ, Fruchart JC. Combination lipid therapy in type 2 diabetes. N Engl J Med 2010;363:692-4.

4. Tenenbaum A, Klempfner R, Fisman EZ. Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor. Cardiovasc Diabetol 2014;13:159.

5. Hermans MP, Ahn SA, Rousseau MF. Parental brevity linked to cardiometabolic risk in descendants. J Diab Complic 2014;28:141-6.

6. Hermans MP, Ahn SA, Rousseau MF. How to transform a metabolic syndrome score in an insulin sensitivity value ? Diabetes Metab Res Rev 2016;32:87-94.

Key words type 2 diabetes; residual cardiovascular risk; silent coronary artery disease; atherogenic dyslipidaemia; triglyceride