Physicians' Academy for Cardiovascular Education

Lp(a) cut-off values are applicable to calcific aortic valve disease in white and black individuals

Cao J, et al. Arterioscler Thromb Vasc Biol. 2016


Lipoprotein(a) Levels Are Associated With Subclinical Calcific Aortic Valve Disease in White and Black Individuals. The Multi-Ethnic Study of Atherosclerosis

Cao J, Steffen BT, Budoff M, et al.
Arterioscler Thromb Vasc Biol. 2016;36: published online ahead of print
 

Background

Subclinical CAVD, that is present in 15% to 40% of adults depending on age and race/ethnicity, and is expected to increase with the aging population,  may advance to valve stenosis and obstruction [1,2]. Aortic valve calcification (AVC) is a subclinical from of calcific aortic valve disease (CAVD) and an independent risk factor for CV disease [3,4]. AVC can progress to CAVD, particularly if certain CHD risk factors are present, like for example age, sex, hypertension, smoking, type II diabetes, hypercholesterolemia, and elevated concentrations of Lp(a)  [5,6]. However, it has not been investigated whether the Lp(a) cut-off values used in clinical laboratories (30 and 50 mg/dL) contribute to the identification of subclinical CAVD and its severity. Another open question is related to the potential differences between multiple races/ethnicities. Race-based differences in median Lp(a) levels have been reported according to which, black individuals typically have two- or three-fold higher Lp(a) levels compared with whites or Hispanics [7]. Interestingly, these Lp(a) levels did not translate into a two- or three-fold higher CHD risk [8].
In this analysis, the relationship between elevated Lp(a) levels and the presence of subclinical CAVD and the degree of AVC was examined in 4,678 participants of the Multi-Ethnic Study of Atherosclerosis (MESA).
 

Main results

• Associations between Lp(a) levels and the presence of AVC:
  • in the entire sample: adjusted RR: 1.11; 95% CI: 1.02–1.21; P=0.02
  • in white participants: RR: 1.19; 95% CI: 1.06–1.33; P=0.0023
  • in black participants: RR: 1.26; 95% CI: 0.97–1.65; P=0.088
  • in Hispanics or Chinese Americans: no significant associations
• The conventional 30 mg/dL Lp(a) clinical cutoff:  
  • was associated with AVC in white participants (RR: 1.56; 95% CI: 1.24–1.96)  
  • was borderline significant in black participants (RR: 1.55; 95% CI: 0.98–2.44, P=0.059)  
• Whites with levels ≥50 mg/dL also showed higher prevalence of AVC (RR: 1.72; 95% CI: 1.36–2.17) than those below this level
• Lp(a) (per 1 log unit) was associated with the severity of AVC:
  • in black participants: OR: 1.48; 95% CI: 1.18–1.87
  • in white participants: OR: 1.33; 95% CI: 1.17–1.51
 

Conclusion

In a large multiethnic cohort, significant associations between Lp(a) levels and subclinical CAVD were observed in black and white individuals, but not in Hispanic and Chinese Americans. The Lp(a) cutoff values that are currently used to assess CV risk seem to be applicable to CAVD, although race/ethnicity may be important in the selection of these cut-off values.
 
Find this article online at http://atvb.ahajournals.org/content/early/2016/03/03/ATVBAHA.115.306683.abstract
 

References

1. Smith JG, Luk K, Schulz CA, et al. Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) Extracoronary Calcium Working Group. Association of low-density lipoprotein cholesterol-related genetic variants with aortic valve calcium and incident aortic stenosis. JAMA.2014;312:1764–1771
2. Thaden JJ, Nkomo VT, Enriquez-Sarano M. The global burden of aortic stenosis. Prog Cardiovasc Dis. 2014;56:565–571
3. Owens DS, Budoff MJ, Katz R, et al. Aortic valve calcium independently predicts coronary and cardiovascular events in a primary prevention population. JACC Cardiovasc Imaging. 2012;5:619–625
4. Otto CM, Burwash IG, Legget ME, et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation. 1997;95:2262–2270
5. Yutzey KE, Demer LL, Body SC, et al. Calcific aortic valve disease: a consensus summary from the Alliance of Investigators on Calcific Aortic Valve Disease. Arterioscler Thromb Vasc Biol.2014;34:2387–2393
6. Kamstrup PR, Tybjarg-Hansen A, Nordestgaard BG. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol. 2014;63:470–477
7. Marcovina SM, Albers JJ, Wijsman E, et al. Differences in Lp[a] concentrations and apo[a] polymorphs between black and white Americans. J Lipid Res. 1996;37:2569–2585
8. Guan W, Cao J, Steffen BT, et al. Race is a key variable in assigning lipoprotein(a) cutoff values for coronary heart disease risk assessment: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2015;35:996–1001