Triglyceride plus HDL-C level identifies subpopulations at increased risk of CHD or stroke

Triglyceride and HDL-C Dyslipidemia and Risks of Coronary Heart Disease and Ischemic Stroke by Glycemic Dysregulation Status: The Strong Heart Study

Literature - Lee JS, Chang P-Y, Zhang Y, et al. - Diabetes Care 2017; published online ahead of print

Background

High triglyceride (TG) levels and low HDL-C levels, which are risk factors for coronary heart disease (CHD) and ischaemic stroke, remain prevalent in statin-treated patients [1-3]. It is important to elucidate whether the risk of incident CHD or ischaemic stroke is different for distinct populations [4,5].

In this study, it was evaluated whether the association of high TG and low HDL-C levels with increased risk of CHD and ischaemic stroke, depends on diabetes mellitus (DM) status, gender and LDL-C levels, in a population of American Indians who have a high prevalence of obesity and diabetes (Strong Heart Study [SHS]).

Main results

  • Out of 3,216 individuals, 37% had normal TG and normal HDL-C levels, 30% had normal TG and low HDL-C levels, 24% had high TG and low HDL-C levels, and 9% had high TG and normal HDL-C levels.
  • During a median follow-up time of 17.7 years (IQR: 15.2-18.6 years), 789 participants had incident CHD (202 were fatal) and 158 participants had incident ischaemic stroke (11 were fatal).
  • Women without DM had the lowest incidence rates of CHD and stroke (7.6 and 1.9 per 1,000 person-years, respectively). Men with DM had the highest incidence of CHD (39.1 per 1,000 person-years). Men and women with DM had similar rates of stroke.
  • High TG levels were associated with a 19% greater hazard of CHD (95% CI: 1.00–1.42) and low HDL-C levels were associated with a 17% greater hazard of CHD (95% CI: 0.99–1.35) compared with those with normal TG and HDL-C levels.
  • Compared with normal TG levels, high TG levels were associated with an adjusted HR estimate of 1.28 for stroke. Compared with normal HDL-C, low HDL-C levels were associated with an adjusted HR of 1.35 for stroke.
  • High TG and low HDL-C levels were associated with a 32% greater adjusted hazard of CHD (95% CI: 1.06–1.64) and an adjusted HR estimate of 1.46 for incident ischaemic stroke (95% CI: 0.92–2.33) compared with normal TG and HDL-C levels.
  • In diabetic participants, high TG levels alone were associated with an increased CHD risk (HR: 1.47; 95% CI: 1.08–2.00) and increased HDL-C levels alone were associated with reduced stroke risk (HR: 0.72; 95% CI: 0.53–0.97). The relationship between TG-HDL status and CHD and stroke risk depended on diabetes status (P interaction = 0.003).
  • High TG and low HDL-C levels were associated with a 1.54-fold greater hazard of incident CHD (95% CI: 1.15–2.06) and a 2.13-fold hazard of incident stroke (95% CI: 1.06–4.29) in participants with DM. These relationships were not observed in non-diabetic patients.
  • In participants with LDL-C levels of ≥130 mg/dL, high TG and low HDL-C levels were associated with an adjusted HR of 1.42 (95% CI: 1.02–1.97), and normal TG and low HDL-C levels were associated with an HR of 1.48 (95% CI: 1.07–2.05). No associations were observed in those with LDL-C lower than 130 mg/dL. P interaction for TG-HDL status and CHD risk versus LDL-C level was 0.064.
  • LDL-C level did not appear to modify TG-HDL status in relation to ischemic stroke (P value for interaction = 0.435).
  • Sex was not observed to modify the relationships of TG-HDL status to incident CHD or stroke risks (P value for interaction = 0.827 for CHD, P value for interaction = 0.887 for stroke).

Conclusion

In a prospective cohort study, high fasting TG levels in combination with low HDL-C levels were associated with increased risks of incident CHD and ischaemic stroke, particularly in patients with diabetes or with an LDL-C level of ≥130 mg/dL, independently of other CVD risk factors. These results may contribute to the optimisation of lipid-lowering therapies.

References

1. Di Angelantonio E, Sarwar N, Perry P, et al.; Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009;302:1993–2000

2. Tanne D, Koren-Morag N, Graff E, et al. Blood lipids and first-ever ischemic stroke/transient ischemic attack in the Bezafibrate Infarction Prevention (BIP) Registry: high triglycerides constitute an independent risk factor. Circulation 2001;104:2892–2897

3. O’Donnell MJ, Xavier D, Liu L, et al.; INTERSTROKE investigators. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case control study. Lancet 2010;376:112–123

4. Jeppesen J, Hein HO, Suadicani P, et al. Low triglycerides-high high-density lipoprotein cholesterol and risk of ischemic heart disease. Arch Intern Med 2001;161:361–366

5. Abdel-Maksoud MF, Eckel RH, Hamman RF, et al. Risk of coronary heart disease is associated with triglycerides and high-density lipoprotein cholesterol in women and non high-density lipoprotein cholesterol in men. J Clin Lipidol 2012;6:374–381

Find this article online at Diabetes Care

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