Results showed that concentrations of very low-density lipoproteins (not detected in current cholesterol tests) were as strongly associated with the risk of myocardial infarction and ischemic stroke as low-density lipoprotein (LDL) particles. This major finding challenges the accepted view that lipids are a risk factor for myocardial infarction but only a weak predictor for ischemic stroke. Surprisingly, none of 61 NMR-quantified measurements of lipoprotein particle concentrations, compositions, size or apolipoproteins were found to associate with intracerebral hemorrhage. Another novel finding was that triglycerides in high-density lipoproteins were found to associate with an increased risk of myocardial infarction. This is important as there has been conflicting evidence about the causal effect of high-density lipoprotein cholesterol (also dubbed “good cholesterol”) on CVD risk.

Overall, concentrations of very low-density lipoproteins and remnant cholesterol were found to be more strongly associated with CVD risk than LDL-C levels, reinforcing recent large-scale Mendelian randomization studies that concluded remnant cholesterol in very low-density lipoproteins may play a key role in the development of CVD. GlycA (a well-reported NMR-signal that marks inflammation) was found to strongly associate with myocardial infarction, ischemic stroke and intracerebral hemorrhage risk, suggesting that inflammatory pathways underpin the development of all three vascular diseases. [1, 2]

Major findings like these suggest that the future focus of drug treatments for cardiovascular disease types could go beyond focusing on reducing levels of LDL-C by also targeting very low-density lipoproteins, fatty acid composition and triglycerides. Through using NMR-based metabolomics, we can screen populations and biobanks to more accurately assess CVD risk. Nightingale’s high-throughput, affordable and standardized NMR-based metabolomics assay provides detailed measurements of lipids and lipoprotein subclasses. Nightingale’s panel includes lipid concentrations and compositions of 14 lipoprotein subclasses, along with measures of amino acids, glycolysis related metabolites, ketone bodies and fatty acids.

An editorial comment in the Journal of Journal of the American College of Cardiology (JACC) makes a strong case for the widespread application of NMR-based lipoprotein and apolipoprotein profiling, it states: “It is time to advance … 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.” [3]

Whilst today’s system of assessing CVD risk may seem thorough, a 2009 study found that nearly half of patients admitted to hospital with heart attacks had normal or low LDL levels when measured. Furthermore, most of the individuals that suffer from cardiovascular events within a population are those who do not score highly with current risk estimation tools. This emphasizes the need for more accurate risk evaluation algorithms. Many now agree that routine cholesterol tests are imprecise and better health data is required. One way of improving the information we gather from patients is to measure the size, density, concentrations and compositions of lipoproteins. Nuclear Magnetic Resonance spectroscopy (NMR) offers an effective solution. High-throughput NMR-based metabolomics can be used measure a wide range of circulating metabolites in a patient’s blood, as well as providing detailed measurements of lipids and lipoproteins. By providing physicians with more relevant data, we are closer than ever to redefining CVD risk.

Key points:

Nightingale’s assay was used to measure 225 metabolites for 4662 individuals (within the China Kadoorie Biobank) at risk of a heart attack (incident myocardial infarction) and stroke (ischemic stroke and intracerebral hemorrhage).

Concentrations of very low-density lipoproteins (VLDL) were as strongly associated with the risk of myocardial infarction and ischemic stroke as low-density lipoprotein (LDL) particles.

Triglycerides in high-density lipoproteins were found to associate with an increased risk of myocardial infarction.

None of 61 measurements of lipoprotein particle concentrations, compositions, size or apolipoproteins were found to associate with intracerebral hemorrhage.

GlycA was found to strongly associate with all three vascular diseases.

High-throughput NMR-based metabolomics may pave the way toward redefining CVD risk.

References:

1. Holmes, M. et al. Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke. Journal of the American College of Cardiology (2018). 71(6). DOI: 10.1016/j.jacc.2017.12.006

2. O’Riordan, M. Beyond LDL Cholesterol: Lipoprotein Particles Linked With MI and Ischemic Stroke. TCTMD (2018). https://www.tctmd.com/news/beyond-ldl-cholesterol-lipoprotein-particles-linked-mi-and-ischemic-stroke

3. Mayr, M. et al. Cardiovascular Risk Beyond Low-Density Lipoprotein Cholesterol. Journal of the American College of Cardiology (2018). 71(6). DOI: 10.1016/j.jacc.2017.12.040