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Remnant cholesterol reduction for atherosclerotic cardiovascular disease prevention: modelling in the Copenhagen
Karen Hvid1,2, Mie Balling1,2,3, Shoaib Afzal1,2,4
1Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Borgmester Ib Juuls vej 73, 2730 Herlev, Denmark.
Insights
Aggressively lowering remnant cholesterol, a cause of atherosclerotic cardiovascular disease (ASCVD), shows potential for significant ASCVD risk reduction in both women and men. This approach may offer greater benefits for statin users and men due to higher baseline risks.
Area of Science:
- Cardiology
- Preventive Medicine
- Lipid Metabolism
Background:
- Elevated remnant cholesterol is a recognized causal factor for atherosclerotic cardiovascular disease (ASCVD).
- The extent to which aggressive reduction of remnant cholesterol impacts ASCVD incidence remains an area of clinical uncertainty.
- Understanding sex-specific and treatment-group differences in response to remnant cholesterol lowering is crucial for personalized risk management.
Purpose of the Study:
- To test the hypothesis that aggressive lowering of remnant cholesterol can lead to substantial ASCVD risk reduction in both women and men.
- To quantify the potential ASCVD risk reduction associated with varying degrees of remnant cholesterol lowering.
- To explore differences in risk reduction between statin users and non-users, and between men and women.
Main Methods:
- Utilized data from the Copenhagen General Population Study, including 56,422 women and 43,952 men recruited between 2003 and 2015.
- Followed participants in national Danish health registries until December 2021 to ascertain incident cases of ASCVD.
- Employed modeling techniques on cohort data to estimate the impact of remnant cholesterol levels on ASCVD risk.
Main Results:
- Over a median follow-up of 12 years, 4,946 women and 6,043 men developed ASCVD.
- In women at very-high cardiovascular risk, a 2 mmol/L reduction in remnant cholesterol (from 3 mmol/L) was associated with an estimated 17% (statin users) and 13% (non-users) absolute 10-year ASCVD risk reduction.
- In men, a similar 2 mmol/L reduction was linked to a 20% (statin users) and 15% (non-users) absolute 10-year ASCVD risk reduction. Reductions of 1 mmol/L also demonstrated significant risk mitigation.
Conclusions:
- Aggressive lowering of remnant cholesterol demonstrates significant potential for reducing ASCVD in both women and men.
- The estimated absolute risk reduction was greater in statin users compared to non-users, and in men compared to women.
- These differences are likely attributable to higher baseline absolute cardiovascular risk observed in statin users and men.
Aims:
Elevated remnant cholesterol is a causal factor for atherosclerotic cardiovascular disease (ASCVD); however, whether aggressive lowering will reduce ASCVD is unclear. In women and men, we tested the hypothesis that aggressive lowering of remnant cholesterol has the potential for substantial ASCVD reduction. This was tested using modelling of cohort data.
Methods And Results:
From the Copenhagen General Population Study, 56 422 women and 43 952 men without a history of ASCVD were recruited from 2003 through 2015. They were subsequently followed in national Danish health registries until December 2021 for incident ASCVD. During a median follow-up of 12 years, 4946 women and 6043 men developed ASCVD. In women at very-high cardiovascular risk, 2 mmol/L (77 mg/dL) lower levels of remnant cholesterol from 3 mmol/L (116 mg/dL) likely reduces absolute 10-year risk of ASCVD by 17 and 13% in statin users and non-users; corresponding values in men were 20 and 15%, respectively. Corresponding values by 1 mmol/L (39 mg/dL) lower remnant cholesterol were 10 and 7% in women and 11 and 9% in men, respectively. Similar values are also provided for lower starting remnant cholesterol levels, different lowering of remnant cholesterol, and lower baseline cardiovascular risk.
Conclusion:
In women and men, aggressive lowering of remnant cholesterol has the potential for substantial ASCVD reduction. Estimated absolute risk reduction was larger in statin users vs. non-users and in men vs. women, likely because statin users vs. non-user and men vs. women are at higher baseline absolute risk.
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