Original Research

Lipoprotein(a) Elevation: A New Diagnostic Code with Relevance to Service Members and Veterans

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Lifestyle and Cardiovascular Health

It is noteworthy that the Lp(a) genetic risks can also be modified by lifestyle risk reduction even in the absence of significant blood level reductions. For example, Khera and colleagues constructed a genetic risk profile for CVD that included genes related to Lp(a). 116 Subjects with high genetic risk were more likely to experience CVD events compared with subjects with low genetic risk. However, risks for CVD were attenuated by 4 healthy lifestyle factors: current nonsmoker, body mass index < 30, at least weekly physical activity, and a healthy diet. Subjects with high genetic risk and an unhealthy lifestyle (0 or 1 of the 4 healthy lifestyle factors) were the most likely to develop CVD (Hazard ratio [HR], 3.5), but that risk was lower for subjects with healthy (3 or 4 of the 4 healthy lifestyle factors) and intermediate lifestyles (2 of the 4 healthy lifestyle factors) (HR, 1.9 and 2.2, respectively), despite despite high genetic risk for CVD.

While the independent CVD risk associated with elevated Lp(a) does not appear to be responsive to lifestyle risk reduction alone, certainly elevated LDLC and traditional risk factors can increase the overall CVD risk and are worthy of preventive interventions. In particular, inflammation from any source exacerbates CVD risk. Proatherogenic diet, insufficient sleep, lack of exercise, and maladaptive stress responses are other targets for personalized CVD risk reduction. 28,117 Studies of dietary modifications and other lifestyle factors have shown reduced risk of CVD events, despite lack of reduction in Lp(a) levels. 119,120 It is noteworthy that statin therapy (with or without ezetimibe) fails to impact CAVS progression, likely because statins either raise or have no effect on Lp(a) levels. 92,119

Until recently, there has been no evidence supporting any therapeutic intervention causing clinically meaningful reductions in Lp(a). Table 4 lists major drug classes and their effects on Lp(a) and CVD outcomes; however, a detailed discussion of each of these therapies is beyond the scope of this review. Drugs that reduce Lp(a) by 20-30% have varying effects on CVD outcomes, from no effect 122,123 to a 10% to 20% decrease in CVD events when compared with a placebo. 124,125 Because these drugs also produce substantial reductions in LDLC, it is not possible to determine how much of the beneficial effects are due to reductions in Lp(a).

Lipoprotein apheresis produces profound reductions in Lp(a) of 60 to 80% in very highrisk populations. 69,126 Within-subjects comparisons show up to 80% reductions in CVD events, relative to event rates prior to treatment initiation. 69,127 Early trials of antisense oligonucleotide against apo(a) therapies show potential to produce similar outcomes. 128,129 These treatments may be particularly effective in patients with isolated Lp(a) elevations.


Lp(a) elevation is a major contributor to cardiovascular disease risk and has been recognized as an ICD-10-CM coded clinical diagnosis, the first laboratory abnormality to be defined a clinical disease in the asymptomatic healthy young individuals. This change addresses currently under- diagnosed CVD risk independent of LDLC reduction strategies. A brief overview of recent guidelines for the clinical use of Lp(a) testing from the American Heart Association 43,151 and the National Lipid Association52 can be found in Table 5. Although drug therapies for lowering Lp(a) levels remain limited, new treatment options are actively being developed.

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