Remnant Cholesterol Predicts CV risk in T2D


In addition to the growing body of evidence that elevated residual cholesterol (residual cholesterol) provides a complementary and independent predictor of the risk of major cardiovascular events (MACE), a new analysis shows that this biomarker has prognostic value, especially in patients with type 2 diabetes. (SD2). ).

In a retrospective analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, each increase in the standard deviation of residual C was associated with a 7% increase in risk of MACE (P = 0.004) after adjusting for several risk factors. including other cholesterol values.

“In type 2 diabetes, residual cholesterol levels are associated with MACE regardless of LDL cholesterol levels,” said a team of researchers led by Liyao Fu, MD, from Xiangya Second Hospital of Central South University, Changsha, China.


Remnant-C is one of the components of triglyceride-rich lipoproteins. In triglyceride-rich lipoproteins, the C residue has become a major focus of efforts to explain residual CV risk, according to the researchers.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors such as LDL cholesterol (LDL-C) are under control.

“Our primary results indicate that baseline calculated levels of residual C were associated with MACE regardless of clinical phenotypes, lifestyle factors associated with cardiovascular risk, and lipid-lowering treatment,” the authors of the analysis said.


In a post hoc analysis of the ACCORD study, which evaluated the effects of intensive glucose lowering in T2DM more than 10 years ago, data were obtained on residual cholesterol over an average of 8.8 years of follow-up in 9650 patients with T2DM. During this period, 1815 people (17.8%) developed MACE.

Multiple analyzes confirm the predictive value of Remnant-C

In addition to a 7% increase in MACE for each increase in the standard deviation of residual C when calculated as a continuous variable, other analyzes showed the same story.


This included an assessment of the C residue tertiles. Not only was there a significant trend (P < 0.001) for greater risk with each higher baseline residue-C tertile, those with the highest tertile had a 38% higher risk of MACE. than those with the lowest tertile (hazard ratio, 1.38; P < 0.001) after adjusting for confounding factors.

The same pattern was observed for several components of MACE, such as CV death and non-fatal myocardial infarction, when comparing residue-C tertiles.

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Visit-to-visit variability in residual C during follow-up has also been associated with an increased risk of MACE. On a logarithmic basis, MACE risk increased by about 40% across all three risk adjustment models. These models included adjustments for various sets of confounding factors such as gender, age, blood pressure, history of cardiovascular disease, and glucose levels. On an unadjusted basis, the risk increased by about 50% (HR 1.52; P < 0.001).


With regard to visit-to-visit variability in residual-C, the largest effect was on the risk of non-fatal MI across models. In Model 3, for example, after adjusting for most confounders, risk almost doubled (RR 1.92; P < 0.001). In contrast, no association was found between visit-to-visit variability and non-fatal stroke.

In a discordant analysis that was performed to examine the relative risk of residual cholesterol independent of LDL cholesterol levels, it was found that those with a residual cholesterol level of at least 31 mg/dL had a higher risk of MACE regardless of LDL cholesterol level. C. However, the risk was higher if both residual cholesterol and LDL cholesterol were elevated. For example, the risk was increased by 22% for patients with LDL-C at or below 100 mg/dL and a residual cholesterol level of at least 31 mg/dL (HR, 1.22; P = 0.015), but rose to 37% for those with LDL cholesterol levels above 100 mg/dL if residual cholesterol is at least 31 mg/dL (HR, 1.38; P = 0.007).

Remnant-C shows predictive value in other risk groups

Although this study suggests an important predictive value for residual CV in T2DM, there are numerous studies suggesting that it has a predictive value in other risk groups, such as those with a history of cardiovascular disease. This includes a study published earlier this year with a 10-year follow-up of 41,928 patients in Denmark. Combined with other risk factors, residual-C significantly improved the accuracy of event risk over time.


Researchers from this previous study, as well as from the new study of patients with type 2 diabetes, predict that residue-C will eventually be included in the recommendations.

According to Shi Tai, MD, co-author of the T2DM study, residue C “may allow the development of specific preventive and therapeutic approaches” to cardiovascular risk in patients with T2DM.

T2DM patients “with elevated levels of residual plasma cholesterol represent a special population that deserves more attention in terms of residual risk,” said Tai, from the Department of Cardiovascular Medicine at South Central China Hospital.

Great interest, but ready for guidelines?

This is an important line of current research, according to Christy M. Ballantyne, MD, professor of medicine at Baylor College of Medicine, Houston.

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“There is a lot of interest from both clinicians and researchers to find an easy way to identify high residual risk patients on statin therapy,” he said. He believes that Remnant-C has a future in this regard.

“Remnant-C is not on the current recommendations,” he said in an interview, but suggested that there is now a significant amount of data to suggest it could be added if it is confirmed in further studies.

“Remnant-C is easy to calculate and can now be useful in practice to identify patients who require more aggressive therapy to reduce risk and may be useful in identifying patients for clinical trials who would benefit from new therapies in development.” , – he said. .

However, the clinical relevance of therapy directed at triglyceride-rich lipoproteins in general or their components, including triglycerides or residue C, has never been demonstrated, notes Peter WF Wilson, MD, PhD.

“Higher fasting or non-fasting triglyceride levels or their substitutes have been shown to be associated with an increased risk of cardiovascular disease in observational studies, but the importance of such measurements in people already on very aggressive LDL cholesterol-lowering therapy is unknown.” said Wilson, director of the division of epidemiology and genomic medicine at Emory School of Medicine, Atlanta.

Wilson co-authored an editorial that accompanied the previously published Danish study on residue-C. In his editorial, he suggested that remnant-C held promise for a better understanding of residual risk, but when informed of this latest data, he highlighted the lack of support for clinical relevance.

“Unfortunately, clinical trials have generally not shown that lowering triglycerides [to favorably alter remnant-C] in this situation, it favorably affects the risk of developing cardiovascular diseases, ”he said in an interview. This does not rule out residual-C as a target risk factor, but these data are needed.

Fu, Tai, and Wilson report no potential conflicts of interest. Ballantyne has financial relationships with over 25 pharmaceutical companies, including several that manufacture products used to treat lipid abnormalities.

This article originally appeared on, part of the Medscape professional network.


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