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Elevated apolipoprotein C-III associated with higher trigylcerides, CAC score in patients with diabetes
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In patients with diabetes but no CHD, elevated levels of plasma apolipoprotein C-III were associated with higher trigylcerides and coronary artery calcification, according to new findings.
The results support the hypothesis that inhibiting apolipoprotein C-III (ApoC-III) could lead to improved cardiometabolic phenotypes and possibly reduced CV risk, the researchers wrote.
“There is now a lot of interest in inhibiting ApoC-III, and I expect we will see a lot of trials coming up,” Arman Qamar, MD, from the division of cardiovascular medicine at Brigham and Women’s Hospital and Harvard Medical School, told Cardiology Today. “If we show that inhibiting ApoC-III improves outcomes, that might become part of our standard of care in the future. This particular pathway is very promising to further reduce the risk of patients who are at risk for adverse CV events.”
Arman Qamar
Prior research showed that people with genes predisposing them to low ApoC-III levels had low triglyceride levels and low risk for CHD and ischemic CVD.
“It is the same thing that happened with PCSK9,” Qamar said in an interview.
Qamar and colleagues analyzed the relationship between ApoC-III, triglycerides and coronary artery calcification (CAC) in 1,422 patients with type 2 diabetes but without clinically manifest CHD.
They found that ApoC-III levels were positively correlated with total cholesterol (Spearman r = 0.36), triglycerides (r = 0.59), LDL (r = 0.16), fasting glucose (r = 0.16) and glycosylated hemoglobin (r = 0.12; P < .0001 for all).
When the researchers adjusted for age, sex and race, ApoC-III levels were positively associated with CAC (Tobit regression ratio = 1.78; 95% CI, 1.27-2.5 per standard deviation increase in ApoC-III; P < .001).
However, adjusting for triglycerides (Tobit regression ratio = 1.43; 95% CI, 0.94-2.18 per standard deviation increase in ApoC-III; P = .086) and very LDL (Tobit regression ratio = 1.14; 95% CI, 0.75-1.71 per standard deviation increase in ApoC-III; P = .53) attenuated the findings.
“What we discovered was, if you have high ApoC-III levels, you will have high levels of triglycerides, but also, surprisingly, you will have high levels of LDL, and you are also more likely to have higher levels of blood glucose,” Qamar told Cardiology Today. “But importantly, [patients with high ApoC-III levels] did have increased risk for atherosclerosis, and all of this seemed to be driven by triglycerides. What we propose is that … inhibition of this particular pathway will not only lead to lowering triglycerides, but might also cause regression of atherosclerosis.”
The association is now being studied in people without diabetes, Qamar said. – by Erik Swain
For more information:
Arman Qamar, MD, can be reached at Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115; email: mqamar@partners.org.
Disclosure: The researchers report no relevant financial disclosures.
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