Dyslipidemia, Coronary Artery Calcium, and Incident Atherosclerotic Cardiovascular Disease: Implications for Statin Therapy from the Multi-Ethnic Study of Atherosclerosis.

Martin SS, Blaha MJ, Blankstein R et al.
Circulation. 2013 Oct 20. [Epub ahead of print]

Background

International clinical practice guidelines highlight the importance of matching the use and intensity of statin therapy with the absolute risk of atherosclerotic cardiovascular disease (CVD)[1-4]. Indeed patients with similar absolute risks of CVD, who achieved similar absolute LDL-c reductions, have benefitted to a similar extend from therapy in trials, irrespective of baseline level of dyslipidemia [5].
Coronary artery calcium (CAC) is a non-invasive measure of subclinical coronary atherosclerosis, which improves absolute risk assessment, in addition to traditional risk factors [6-9]. It is of particular use in individuals at intermediate risk [8,9], and seems superior to other novel risk markers [9]. Guidelines therefore now recommend (class IIa recommendation) CAC measurement in asymptomatic intermediate-risk patients (10-20% 10-year risk) and (class IIb) low- to intermediate-risk patients (6-10% 10-year risk) [10].
CAC measurement is currently not recommended in dyslipidaemia guidelines [1-4]. In order to explore its potential role in such guidelines, this study evaluated the relationship between CAC and dyslipidemia in relation to CVD outcomes in the Multi-ethnic Study of Atherosclerosis (MESA)[6,11]. Dyslipidemia was categorized as the number of lipid abnormalities (LAs): high LDL-c, low HDL-c and/or high triglyceride levels, since counting LAs may reflect the way that clinicians and patients think about increasing burden of dyslipidemia. In parallel, dyslipidemia was also classified by TC/HDL-c quartiles.

Main results

• Of 6814 adults (45-85 years old), free of clinical CVD, of the general population that enrolled in this study, 36% participants had 0 LA, 37% had 1 LA, 22% had 2 LA and 6% had 3 LA.
• 58% of individuals without LA had CAC=0. CAC scores of 1-99 and >100 were seen in 22% and 20% respectively in individuals with 0 LA. In subjects with 3 LA, the respective prevalences were 29% and 21%. Categorising dyslipidemia by TC/HDL-c quartiles yielded similar results.
• CVD rate was 7.1 per 1000 person-years (py, 95%CI: 5.8-8.7) for those without LA, and 9.3 (95%CI: 7.8-11.0), 11.6 (95%CI: 9.5-14.2) and 13.9 (95%CI: 9.8-19.8) per 1000 py in those with 1, 2 and 3 LA respectively.
  CVD event rates were 3.0 per 1000 py (95%CI: 2.4-3.9) for those with CAC=0, and 9.8 (95%CI: 8.0-12.0) and 26.5 (95%CI: 23.0-30.5) per 1000 py in those with CAC of 1-99 and >100 respectively.

• Individuals with no LA and CAC>100 had a higher event rate as compared to individuals with 3 LA but CAC=0 (22.2 vs. 6.2 vs. 1000 py).
• The ‘hard CVD event’ rates (myocardial infarction, resuscitated cardiac arrest, stroke, CV death) were 2.5 per 1000 py (95%CI: 1.9-2.3) in subjects with CAC=0, 7.7 per 1000 py (95%CI: 6.1-9.6) in those with CAC=1-99 and 16.9 per 1000 py (95%CI: 14.2-20.1) in those with CAC>100.

Conclusion

This study evaluated two paradigms of risk assessment in the multi-ethnic, asymptomatic general adult community: dyslipidemia (risk factor) and CAC (measurable atherosclerosis). CAC stratifies CVD risk irrespective of the burden of dyslipidemia, and regardless of how dyslipidemia is defined.
About one in five individuals without any dyslipidemia by traditional definitions, had CAC>100, and high absolute CVD risk. Detecting subclinical atherosclerosis by CAC may facilitate more reliable risk assessment, and prioritising statin treatment in high-risk individuals.

References

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