February 27, 2018
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Lipoproteins, lipids tied to MI, ischemic stroke risk, not brain bleeds

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Lipoproteins and lipids were consistently linked to MI and ischemic stroke risk, but the same was not true for intracerebral hemorrhage, according to new data.

“Observational studies and randomized controlled trials have demonstrated that LDL is one of the most important modifiable and causal risk factors for CHD and ischemic stroke,” Michael V. Holmes, MD, PhD, the University of Oxford, England, and colleagues wrote. “The relationship of LDL with risk of intracerebral hemorrhage is less clear, and the role of other lipids (eg, HDL and triglycerides) in the etiology of CVD subtypes is not so well established.”

Holmes and colleagues conducted a nested case-control study consisting of patients aged 30 to 79 years to investigate the associations of plasma metabolic markers with risks for incident MI, ischemic stroke and intracerebral hemorrhage. In the cohort, there were 912 patients with MI, 1,146 patients with ischemic stroke, 1,138 with intracerebral hemorrhage and 1,466 controls.

Association with MI, stroke

The results showed that VLDL, intermediate-density lipoprotein and LDL particles were positively associated with MI, as adjusted ORs per 1 standard deviation increment ranged from 1.18 (95% CI, 1.07-1.29) for extremely large VLDL to 1.3 (95% CI, 1.19-1.44) for small VLDL.

Holmes and colleagues also found that most VLDL particle subclasses were associated with ischemic stroke.

HDL particles other than small HDL particles were inversely associated with MI, and no lipoprotein particles were associated with intracerebral hemorrhage, according to the researchers.

There was an inverse association between cholesterol in large HDL with MI and ischemic stroke (OR = 0.79 and 0.88, respectively), but the same was not true for cholesterol in small HDL (OR = 0.99 and 1.06, respectively), Holmes and colleagues wrote.

The results of the study showed that triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI. The researchers found a similar pattern for ischemic stroke.

MI, ischemic stroke and intracerebral hemorrhage were linked to glycoprotein acetyls, ketone bodies, glucose and docosahexaenoic acid.

There was a concordant association between 225 metabolic markers and MI and ischemic stroke, but not intracerebral hemorrhage.

“Although lipids and lipoproteins may play a less important role in the development of [intracerebral hemorrhage] as compared with MI or [ischemic stroke], inflammation may play a role in MI, [ischemic stroke] and [intracerebral hemorrhage],” the researchers wrote. “Large-scale studies using genetic approaches are needed to clarify the causal roles of individual lipoproteins, lipid constituents and other metabolic markers for subtypes of stroke and MI.”

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New era of lipid management

In a related editorial, Manuel Mayr, MD, from the King’s British Heart Foundation Centre at King’s College London, and colleagues, wrote: “We are entering a new era of lipid management. With a growing armamentarium of lipid-lowering therapies, patients can be more readily treated to achieve the recommended LDL target therapies.

“Besides LDL, the therapeutic focus may broaden to tackle the residual CVD risk and include VLDL and [triglycerides], as well as fatty acid composition and other apolipoproteins, that is, lipoprotein(a),” they wrote. “It is time to advance [nuclear] MR spectroscopy and mass spectrometry technologies for lipoprotein and apolipoprotein profiling to meet the high throughput, low cost and standardization required for potential clinical use. The application of multiomics technologies may pave the way toward redefining CVD risk.” – by Dave Quaile

Disclosure s : Holmes reports he receives support from the National Institute for Health Research Oxford Biomedical Research Center. Mayr reports he receives grant support from the British Heart Foundation. Please see the study and editorial for all other authors’ relevant financial disclosures.