Combination of high Lp(a) and high BMI confers highest risk of calcific aortic valve disease

Lipoprotein(a) and Body Mass Compound the Risk of Calcific Aortic Valve Disease

Literature - Kaltoft M, Langsted A, Afzal S et al. - J Am Coll Cardiol. 2022 Feb 15;79(6):545-558. doi: 10.1016/j.jacc.2021.11.043.

Introduction and methods

Background

Previous studies have demonstrated that elevated Lp(a) and BMI are separately associated with increased risk of calcific aortic valve disease (CAVD) [1-7]. However, it remains unknown whether a combination of these two risk factors can identify individuals at the highest risk of CAVD.

Aim of the study

This study evaluated the association between high Lp(a) and high BMI with risk of CAVD, and assessed the 10-year absolute risk for the most important risk factors of CAVD.

Methods

A total of 69,988 individuals from the Copenhagen General Population Study without CAVD and with information on both Lp(a) levels and BMI were included in this study. After a median follow-up of 7,4 years, the association between high Lp(a) and high BMI with risk of CAVD was evaluated. In head-to-head analyses comparing Lp(a) with BMI, Lp(a) and BMI were both categorized into groups of 1st to 49th, 50th to 89th, and 90th to 100th percentiles. For calculation of 10-year absolute risks, Lp(a)was categorized into the three groups based on clinical cutpoints (≤42 mg/dL [88 nmol/L], 43-79 mg/dL [89-169 nmol/L], and ≥80 mg/dL [170 nmol/L], and BMI was also categorized into three groups (normal weight [18.5-24.9 kg/m²], overweight [25.0-29.9 kg/m²] and obesity [≥30 kg/m²]).

Main results

Association of high Lp(a) and high BMI separately with CAVD

  • The multivariable adjusted HR for CAVD in individuals with Lp(a) levels in the top 10% (90th to 100th percentiles) was 1.86 (95% CI 1.57-2.21), compared with individuals with Lp(a) levels in the bottom 50% (1st to 49th percentiles). The corresponding HR for individuals with BMI in the top 10%, compared to BMI in the bottom 50%, was 1.79 (95% CI 1.49-2.14).

Association between the combination of high Lp(a) and high BMI with CAVD

  • Multivariable adjusted HRs for CAVD increased with both higher Lp(a) and higher BMI. There was no interaction between Lp(a) and BMI in their association with CAVD (P for interaction =0.92).
  • The multivariable adjusted HR for CAVD in individuals with both Lp(a) and BMI in the top 10% was 3.5 (95% CI 2.5-5.1), compared with individuals with Lp(a) and BMI in the bottom 50%.

Absolute 10-year risk of CAVD

  • Absolute 10-year risk of CAVD was higher in men than in women and increased with higher age, Lp(a) and BMI.
  • Absolute 10-year risks were displayed in a table containing the top 4 risk factors for CAVD. Absolute risk ranged from 0.4% (in women with normal BMI, Lp(a) ≤42 mg/dL and in de lowest age category [50-59 years]) to 14% (in men with obesity, Lp(a) ≥80 mg/dL and in the highest age category [70-79 years]).

Conclusion

The combination of Lp(a) levels and BMI in the top 10% conferred a 3.5-fold risk of CAVD compared with both risk factors in the bottom 50%. Absolute 10-year risk of CAVD was higher in men than in women and increased with higher age, Lp(a) and BMI, and ranged from 0.4% to 14%.

References

1. Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013;368:503–512.

2. Kamstrup PR, Tybjaerg-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.

3. Arsenault BJ, Boekholdt SM, Dube MP, et al. Lipoprotein(a) levels, genotype, and incident aortic valve stenosis: a prospective Mendelian randomization study and replication in a casecontrol cohort. Circ Cardiovasc Genet. 2014;7: 304–310.

4. Chen HY, Dufresne L, Burr H, et al. Association of LPA variants with aortic stenosis: a large-scale study using diagnostic and procedural codes from electronic

5. Larsson SC, Wolk A, Hakansson N, Back M. Overall and abdominal obesity and incident aortic valve stenosis: two prospective cohort studies. Eur Heart J. 2017;38:2192–2197.

6. Larsson SC, Back M, Rees JMB, Mason AM, Burgess S. Body mass index and body composition in relation to 14 cardiovascular conditions in UK Biobank: a Mendelian andomization study. Eur Heart J. 2020;41:221–226.

7. Kaltoft M, Langsted A, Nordestgaard BG.Obesity as a causal risk factor for aortic valve stenosis. J Am Coll Cardiol. 2020;75:163–176.

Find this article online at J Am Coll Cardiol.

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