Lipoprotein(a) has no major impact on calcification activity in patients with mild to moderate aortic valve stenosis

Abstract

ObjectiveTo assess whether patients with aortic valve stenosis (AS) with elevated lipoprotein(a) (Lp(a)) are characterised by increased valvular calcification activity compared with those with low Lp(a).MethodsWe performed 18F-sodium fluoride (18F-NaF) positron emission tomography/CT in patients with mild to moderate AS (peak aortic jet velocity between 2 and 4 m/s) and high versus low Lp(a) (>50 mg/dL vs <50 mg/dL, respectively). Subjects were matched according to age, gender, peak aortic jet velocity and valve morphology. We used a target to background ratio with the most diseased segment approach to compare 18F-NaF uptake.Results52 individuals (26 matched pairs) were included in the analysis. The mean age was 66.4±5.5 years, 44 (84.6%) were men, and the mean aortic valve velocity was 2.80±0.49 m/s. The median Lp(a) was 79 (64–117) mg/dL and 7 (5–11) mg/dL in the high and low Lp(a) groups, respectively. Systolic blood pressure and low-density-lipoprotein cholesterol (corrected for Lp(a)) were significantly higher in the low Lp(a) group (141±12 mm Hg vs 128±12 mm Hg, 2.5±1.1 mmol/L vs 1.9±0.8 mmol/L). We found no difference in valvular 18F-NaF uptake between the high and low Lp(a) groups (3.02±1.26 vs 3.05±0.96, p=0.902). Linear regression analysis showed valvular calcium score to be the only significant determinant of valvular 18F-NaF uptake (β=0.63; 95% CI 0.38 to 0.88 per 1000 Agatston unit increase, p<0.001). Lp(a) was not associated with 18F-NaF uptake (β=0.17; 95% CI −0.44 to 0.88, p=0.305 for the high Lp(a) group).ConclusionAmong patients with mild to moderate AS, calcification activity is predominantly determined by established calcium burden. The results do not support our hypothesis that Lp(a) is associated with valvular 18F-NaF uptake.

Lipoprotein(a): a risk factor for atherosclerosis and an emerging therapeutic target

“…It seems that the high Lp(a) levels associated with the genetic rs10455872 variant in the LPA locus mediate the increased incidence of CAS and aortic valve replacement 20. However, elevated Lp(a) levels are associated with faster CAS progression7 but not with valvular calcification activity in mild-to-moderate CAS 21. Further research is needed to clarify the role of Lp(a) in CAS.…”

Response to: Correspondence on "Lipoprotein(a) has no major impact on calcification activity in patients with mild to moderate aortic valve stenosis" by Pantelidis et al

“…Pantelidis1 raises several points regarding our manuscript ‘Lipoprotein(a) has no major impact on calcification activity in patients with mild to moderate aortic valve stenosis’. 2 He states that our study results should be interpreted with caution, due to (1) selection bias, (2) the absence of follow-up data and (3) a small sample size.…”

Correspondence on "Lipoprotein(a) has no major impact on calcification activity in patients with mild to moderate aortic valve stenosis" by Kaiser et al

“…This discrepancy, also highlighted by the authors in their report, is analysed by Chan in an editorial response, where he attributes it to the lipid-independent mechanisms mediating the advanced stages of the disease 7. Moreover, the authors speculate that significant differences in the baseline characteristics of the two groups (a difference of 13 mm Hg in systolic blood pressure and one of 0.6 mmol/L in the corrected low-density lipoprotein levels) might be the driving force for this deviation 1. Although such interpretations are profoundly reasonable, we believe it is important to resolve all other masking factors that might undermine the generalisability and validity of the results, before adopting the former.…”

“…The recent work of Kaiser et al ,1 entitled ‘Lipoprotein(a) has no major impact on calcification activity in patients with mild to moderate aortic valve stenosis’, offers one more useful piece of evidence regarding the association of lipoprotein(a) (Lp(a)) with aortic valve (AoV) calcification. Although at first glance, the authors seem to present results contradictory to growing evidence that supports a strong causal relationship between Lp(a) and AoV calcification,2 a closer look seems to explain this deviation, in a way that reminds us of the ‘Abraham Wald’ paradigm, back in the 1940s.…”

“…Against the obvious approach that the most-hit parts should be protected, Wald also considered as important the least-hit areas, claiming that planes receiving fire there might not have ‘survived’ to be accounted for 3. Their seminal work highlighted this form of ‘selection’ bias, which still remains relevant today in the research arena and one can argue that it is also reflected in the study at hand 1…”