Could the omega-3 index predict the risk of cardiovascular disease, chronic kidney disease and associated complications?

  • 12/13/2018

Given that various fatty acids form part of the lipid bilayer of the cell membrane, changes to former could affect their characteristics and, therefore, their biological effects. For instance, omega-3 fatty acids are incorporated into the phospholipid membrane and alter the physico-chemical properties of the membrane structures, modulating cellular inflammatory processes and the growth of apoptosis; docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) reduce key regulators for cytokine transcription from circulating immune cells, thereby reducing inflammatory cytokine production. In more general terms, changes in the fatty acid content of the red blood cell membrane are associated with various conditions: dietary intake of fatty acids during the three months prior to measurement, dyslipidemia and hyperglycaemia.

The prevalence of chronic kidney disease is rising, due to a rising elderly population and increasing numbers of individuals with obesity, hypertension, metabolic syndrome, diabetes and cardiovascular disease. Cardiovascular disease in not just a result of chronic kidney disease, but also its cause. Chronic kidney disease is determined by the presence of albuminuria with a normal glomerular filtration rate (GFR) or a GFR <60 mL/min1.73 m2 without albuminuria. Albuminuria and a low GFR also represent an increased risk of cardiovascular disease. A rise in proteinuria, uncontrolled hypertension, consistently high levels of glucose and dyslipidemia are known factors in the progression of chronic kidney disease. Both conditions are closely related.

Could the omega-3 fatty acid composition of the red blood cell membrane (omega-3 index) predict the risk of cardiovascular disease, chronic kidney disease and associated complications?

Cardiovascular risk:

  • Omega-3 fatty acids reduce the risk of cardiovascular disease, by regulating risk factors (dyslipidemia, high blood pressure, central obesity and inflammation) via multiple molecular pathways.
  • The risk of type 2 diabetes has been negatively associated with omega-3 fatty acid content in the red cell membrane.
  • DHA in serum phospholipids is significantly lower in coronary artery disease, particularly in individuals with metabolic syndrome; it is also negatively related to arterial rigidity in metabolically healthy men.
  • A high red cell concentration of DHA is associated with better endothelial function.
  • The risk of intracranial atherosclerosis is inversely associated with DHA levels in blood phospholipids.
  • The omega-3 index is strongly related to omega-3 fatty acid content in the cardiac tissue and blood phospholipids.
  • An omega-3 index of over 8% is associated with lower mortality due to coronary artery disease (compared to an index below 4% in a meta-analysis of 10 cohorts).

Therefore, the omega-3 fatty acid content of phospholipids and red blood cell membranes could be an important marker for cardiovascular risk.

Renal risk

  • A relationship has been found between high total levels of polyunsaturated fatty acids and a higher GFR in elderly patients.
  • The same study also found that total plasma levels of polyunsaturated fatty acids were inversely associated with urinary excretion of proteins, but only levels of omega-3 fatty acids were inversely associated with the risk of developing kidney failure or death.
  • Another study found that high omega-3 fatty acid content in the red cell membrane is associated with less tubulointerstitial lesion. 
  • After kidney transplantation, patients with lower blood levels of omega-3 fatty acids showed graft dysfunction more rapidly than those with high levels. Low plasma levels of omega-3 fatty acids were positively associated with the development of interstitial fibrosis in the first year after transplantation.
  • Supplementation with omega-3 fatty acids has been shown to reduce the progression of albuminuria in subjects with type 2 diabetes and coronary artery disease.

Circulating levels of omega-3 fatty acids can be a good indicator of kidney function after kidney transplantation.

Prediction of cardiovascular risk and mortality in patients with chronic kidney disease:

  • In dialysis patients, DHA in red blood cell membranes is inversely associated with disease-related mortality.
  • In dialysis patients, levels of saturated and monounsaturated fatty acids are higher, while omega-3 fatty acids are lower; this is associated with lipid disorders and cardiomyopathy.
  • Sudden death during the first year of haemodialysis is negatively related to levels of omega-3 fatty acids, especially those of DHA.
  • In dialysis patients with cardiovascular disease, serum DHA levels are significantly lower in those with atrial fibrillation than in those with normal sinus rhythm.
  • Plasma omega-3 fatty acid levels have been associated with lower heart rates at rest, lower triglyceride concentrations and higher concentrations of high-density lipoproteins (HDL).
  • In kidney transplant recipients, omega-3 fatty acid plasma levels have been inversely associated with lower overall cardiovascular mortality and, in particular, sudden heart death and death due to stroke.

It may be concluded that omega-3 fatty acids have a favourable effect on cardiovascular morbidity and mortality, although some studies have not observed a reduction in cardiovascular risk after supplementation with omega-3 fatty acids. The American Heart Association recommends that patients with chronic kidney disease and heart disease consume omega-3 fatty acids.

The observations described here show that measuring fatty acids, especially omega-3 fatty acids, in both plasma and the red blood cell membrane could be useful for predicting the risk of cardiovascular disease and chronic kidney disease, their progression and possible complications.

Kim OY, Lee SM, An WS. Impact of Blood or Erythrocyte Membrane Fatty Acids for Disease Risk Prediction: Focusing on Cardiovascular Disease and Chronic Kidney Disease. Nutrients. 2018;10(10).


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