Key Points
Question
Is exposure to elevated plasma lipoprotein(a) concentrations associated with hemodynamic progression of aortic stenosis?
Findings
In this meta-analysis of 710 patients from 5 longitudinal clinical studies, those with higher plasma lipoprotein(a) concentrations had a faster rate of progression of aortic stenosis.
Meaning
Randomized clinical trials should be performed to determine whether lipoprotein(a)-lowering therapies influence aortic stenosis progression.
This meta-analysis evaluates lipoprotein(a) concentrations and hemodynamic progression in patients with aortic stenosis.
Abstract
Importance
There are currently no pharmacological treatments available to slow hemodynamic progression of aortic stenosis. Plasma lipoprotein(a) concentrations predict incident aortic stenosis but its association with hemodynamic progression is controversial.
Objective
To determine the association between plasma lipoprotein(a) concentrations and hemodynamic progression in patients with aortic stenosis.
Design, Settings and Participants
The study included patients with aortic stenosis from 5 longitudinal clinical studies conducted from March 2001 to March 2023 in Canada and the UK. Of 757 total patients, data on plasma lipoprotein(a) concentrations and rates of hemodynamic progression assessed by echocardiography were available for 710, who were included in this analysis. Data were analyzed from March 2023 to April 2024.
Exposure
Cohort-specific plasma lipoprotein(a) concentration tertiles.
Main Outcomes and Measures
Hemodynamic aortic stenosis progression on echocardiography as assessed by annualized change in peak aortic jet velocity, mean transvalvular gradient, and aortic valve area.
Results
Among the included patients, 497 (70%) were male and 213 (30%) were female. The mean (SD) age was 65.2 (13.1) years. Patients in the top lipoprotein(a) tertile demonstrated 41% (estimate, 1.41; 95% CI, 1.13-1.75) faster progression of peak aortic jet velocity and 57% (estimate, 1.57; 95% CI, 1.18-2.10) faster progression of mean transvalvular gradient than patients in the bottom tertile. There was no evidence of heterogeneity across the individual cohorts. Progression of aortic valve area was comparable between groups (estimate, 1.23; 95% CI, 0.71-2.12). Similar results were observed when plasma lipoprotein(a) concentrations were treated as a continuous variable.
Conclusions and Relevance
In this study, higher plasma lipoprotein(a) concentrations were associated with faster rates of hemodynamic progression in patients with aortic stenosis. Lowering plasma lipoprotein(a) concentrations warrants further investigation in the prevention and treatment of aortic stenosis.
Introduction
Calcific aortic valve stenosis is the commonest form of valvular heart disease worldwide, affecting almost 3% of the population older than 65 years.1 Recent studies have suggested an association between the plasma concentration of the atherogenic lipoprotein particle, lipoprotein(a), and the risk of incident aortic stenosis.2,3,4 While there are currently no pharmacological treatments approved to prevent or treat aortic stenosis, lipoprotein(a) is now considered a prime therapeutic target for aortic stenosis. Although the evidence supporting lipoprotein(a) as an important initiator of aortic stenosis is strong, whether plasma lipoprotein(a) concentrations predict the progression of aortic stenosis has not been thoroughly established. This is important, as the factors that drive aortic stenosis initiation are not necessarily the same as those that drive disease progression.5 Several studies6,7 have demonstrated an association between plasma lipoprotein(a) concentrations with aortic stenosis progression using echocardiography, computed tomography (CT), and positron emission tomography, while a recent CT study8 did not. Each of these studies has been limited by relatively small sample sizes, and we consequently lack a clear idea of disease progression in patients with and without elevated plasma lipoprotein(a) concentrations. Larger multicenter studies are required, particularly those using echocardiography, as this remains the key imaging technique for clinical decision making that is used globally to assess aortic stenosis severity over time.
The objective of the present study was to assess the association of plasma lipoprotein(a) concentrations with hemodynamic aortic stenosis progression assessed by echocardiography in a meta-analysis of 5 longitudinal clinical study cohorts, including 2 studies in which data associating lipoprotein(a) levels and rate of aortic stenosis progression have not been previously published.
Methods
Study Populations and Laboratory Measurements
All studies conducted received ethical approval from their respective institutional review boards or ethics committees. No further approval was required for this meta-analysis.
The study population comprised patients from 5 prospective cohorts who had a measurement of both plasma lipoprotein(a) concentrations and annualized aortic stenosis progression as assessed by echocardiography. The design and rationale of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial has been described previously9 and included 269 participants with mild to moderate aortic stenosis at baseline (peak aortic jet velocity between 2.5 and 4.0 m/s) who were randomized to rosuvastatin or placebo. Participants were recruited between 2002 and 2005 at 23 Canadian sites. For the current analysis, we included 220 participants from ASTRONOMER with lipoprotein(a) concentrations available as described previously.8 The association of exposure to elevated lipoprotein(a) concentrations and aortic stenosis progression in the Ring of Fire and Scottish Aortic Stenosis and Lipid Lowering Trial (SALTIRE) studies have also been previously documented.7 In the Ring of Fire study, patients aged 50 years and older were recruited from the outpatient department of the Edinburgh Heart Centre, as described previously.10 The SALTIRE study was a prospective trial assessing the efficacy of high-dose statin therapy on aortic stenosis progression in patients with aortic stenosis and peak aortic jet velocity of 2.5 m/s or greater.11 Plasma lipoprotein(a) concentrations were available in 65 of these patients. We also included 2 cohorts where the association between lipoprotein(a) and hemodynamics aortic stenosis progression has not previously been reported. The Metabolic Determinants of the Progression of Aortic Stenosis (PROGRESSA) study is a prospective observational cohort study that included adult asymptomatic patients with at least mild aortic stenosis (peak aortic jet velocity >2.0 m/s) who underwent annual echocardiography. Plasma lipoprotein(a) concentrations were measured in 350 participants by turbidimetric assay using the Tina-quant Lipoprotein(a) Gen.2 system (Cobas integra 400/800, Roche Diagnostics) with the results reported in nanomoles per liter.12,13 The Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis (SALTIRE2) was a prospective trial assessing the efficacy of denosumab or alendronic acid vs placebo on aortic stenosis progression in patients with aortic stenosis with peak aortic jet velocity of 2.5 m/s or greater. The main study results have recently been published.14 In SALTIRE2, plasma lipoprotein(a) concentrations were measured using chemoluminescent immunoassays as previously described,6 and the results reported in nanomoles per liter. In the ASTRONOMER, SALTIRE, and SALTIRE2 randomized clinical trials, the progression of aortic stenosis was comparable in patients receiving the active treatments vs placebo, allowing us to pool all the patients participating in those trials. Because lipoprotein(a) concentrations were measured with different assays across the cohorts, patients were separated into cohort-specific lipoprotein(a) tertiles before meta-analysis.
Echocardiography
Echocardiographic assessments of aortic stenosis severity and hemodynamic progression have been described before for each of the 5 clinical cohorts. In brief, serial echocardiographic examinations were performed in each patient by experienced sonographers according to international guidelines.7,8,14,15 On each scan, assessment was made of the peak aortic valve jet velocity (m/s), the mean transvalvular pressure gradient (mm Hg), and the aortic valve area (cm2) calculated using the continuity equation. Changes in these measurements were calculated for each patient and annualized to account for different follow-up times of participants in the different cohorts. This was performed by calculating the difference in values between the baseline and last follow-up measurements and then dividing this change by the time (in years) between these 2 measures.
Statistical Analyses
The primary outcome for hemodynamic progression was the annual change of peak aortic jet velocity, an established measure of aortic stenosis progression in each cohort. Study participants were separated into tertiles based on the distribution of lipoprotein(a) in each cohort. Two-way analyses of variance followed by Tukey and Dunnett post hoc tests were used to assess the association of lipoprotein(a) concentrations (by tertiles) with annualized changes in selected outcomes. A general linear model was also used to compare the association of exposure to elevated lipoprotein(a) levels (top vs bottom tertile) with peak aortic jet velocity progression and a meta-analysis was performed using the meta package in R version 4.1.3 (R Foundation). The meta-analysis was based on the ratio of least-squares means (tertile 3 vs tertile 1). A similar analytical strategy was used to determine the association between plasma lipoprotein(a) concentrations treated as a continuous variable and aortic jet velocity progression. Because plasma lipoprotein(a) concentrations were not reported in the same units across the cohorts, the effect sizes could not simply be pooled together in this meta-analysis. However, the effect sizes of the correlation coefficients (Pearson r) between plasma lipoprotein(a) concentrations and aortic stenosis progression can be compared. To perform a meta-analysis, we used the ppcor package to assess the correlation between log-transformed plasma lipoprotein(a) concentrations and aortic jet velocity progression and used the meta package to meta-analyze the effect sizes of lipoprotein(a) based on a Fisher z transformation. Exploratory analyses were also performed to investigate the association of exposure to high lipoprotein(a) concentrations with mean gradient and aortic valve area, two other key assessments of aortic stenosis severity recommended by international guidelines. P values less than .05 were considered statistically significant.
Results
This analysis included 757 patients (497 [70%] male and 213 [30%] female; mean [SD] age, 65.2 [13.1] years) from the ASTRONOMER, PROGRESSA, Ring of Fire, SALTIRE, and SALTIRE2 clinical studies who had lipoprotein(a) concentrations, including 710 patients in whom data on annualized aortic stenosis progression based on echocardiography were available. Baseline characteristics of study patients in each cohort are presented in Table, while eTables 1 to 5 in Supplement 1 present baseline characteristics of study patients from each cohort separated into lipoprotein(a) tertiles as well as the lipoprotein(a) thresholds that were selected (top tertile) for each cohort.
Table. Baseline Characteristics of Study Participants.
| Characteristic | ASTRONOMER | PROGRESSA | Ring of Fire | SALTIRE | SALTIRE2 |
|---|---|---|---|---|---|
| Participants, No. | 220 | 228 | 80 | 65 | 164 |
| Age, mean (SD), y | 57.7 (13.1) | 63.9 (13.9) | 72.3 (8.4) | 67.9 (11.1) | 72.7 (7.6) |
| Sex, No. (%) | |||||
| Male | 132 (60.0) | 168 (73.7) | 54 (67.5) | 45 (69.2) | 130 (79.3) |
| Female | 88 (40.0) | 60 (26.3) | 26 (32.5) | 20 (30.8) | 34 (20.7) |
| BMI, mean (SD) | 28.2 (5.6) | 28.5 (4.5) | 27.9 (4.2) | 27.3 (4.5) | 29.9 (5.3) |
| Diabetes, No. (%) | 0 | 55 (24.1) | 14 (17.5) | 2 (3.08) | 37 (22.6) |
| Hypertension, No. (%) | 70 (31.8) | 155 (68.0) | 53 (66.2) | 30 (46.2) | 121 (73.8) |
| Statin, No. (%) | 112 (50.9) | 150 (65.8) | 47 (58.8) | 0 | 111 (67.7) |
| Lipoprotein(a), median (IQR), mg/dL | 29.8 (12.1-76.1) | NA | 17.5 (8.7-60.65) | 11.8 (5.4-36.8) | NA |
| Lipoprotein(a), median (IQR), nmol/L | NA | 19.0 (10.0-94.2) | NA | NA | 19.5 (6.4-69.4) |
| LDL-C, median (IQR), mg/dL | 127.2 (108.0-146.7) | 83.9 (67.7-107.6) | 100.5 (69.6-139.2) | 136.9 (119.7-155.1) | NA |
| HDL-C, median (IQR), mg/dL | 56.0 (46.7-66.0) | 55.1 (46.0-64.2) | 50.3 (42.5-58.0) | 57.6 (47.7-70.0) | NA |
| Triglycerides, median (IQR), mg/dL | 103.5 (75.2-148.2) | 108.5 (76.0-147.91) | 168.3 (106.3-205.9) | 124.0 (88.6-150.6) | NA |
| Creatinine, median (IQR), mg/dL | 0.91 (0.50-1.69) | 0.96 (0.48-2.82) | 1.04 (0.55-1.98) | 1.04 (0.70-1.64) | 0.96 (0.57-1.75) |
| Bicuspid aortic valve, No. (%) | 105 (47.7) | 59 (25.9) | 0 | 0 | 10 (6.1) |
| Peak aortic jet velocity, mean (SD), m/s | 3.17 (0.41) | 2.65 (0.40) | 3.49 (0.90) | 3.34 (0.63) | 3.40 (0.60) |
| Mean transvalvular gradient, mean (SD), mm Hg | 22.5 (7.10) | 16.3 (5.6) | 28.2 (16.4) | 25.0 (10.6) | 25.4 (9.9) |
| Aortic valve area, mean (SD), cm2 | 1.34 (0.42) | 1.26 (0.35) | 1.16 (0.41) | 0.96 (0.36) | 1.08 (0.30) |
Abbreviations: ASTRONOMER, Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); HDL-C, high-density lipoprotein cholesterol, LDL-C, low-density lipoprotein cholesterol; NA, not available; PROGRESSA, Metabolic Determinants of the Progression of Aortic Stenosis; Ring of Fire; SALTIRE, Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression; SALTIRE2, Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis.
Results From Meta-Analysis
Meta-analysis of the data from the 5 studies demonstrated that the highest lipoprotein(a) tertiles were associated with faster hemodynamic progression as assessed by peak aortic valve jet velocity and mean gradient. Indeed, analysis of effect size comparing the progression of the extreme lipoprotein(a) tertiles in a meta-analysis revealed an overall positive association between plasma lipoprotein(a) concentrations and the progression of aortic jet velocity (Figure 1A) with no evidence of heterogeneity across the individual cohorts. Compared to patients in the bottom lipoprotein(a) tertile, those in the top tertile demonstrated a 41% faster progression of peak aortic jet velocity (estimate, 1.41; 95% CI, 1.13-1.75). The association between plasma lipoprotein(a) concentrations as a continuous variable; peak aortic jet velocity progression was also examined. Using this approach, plasma lipoprotein(a) concentrations were again associated with aortic jet velocity progression (Figure 1B) with no evidence of heterogeneity.
Figure 1. Association Between Exposure to Elevated Lipoprotein(a) Levels and Peak Aortic Jet Velocity (Vpeak) Progression in Patients From 5 Cohorts.
Effect sizes and meta-analysis represent the effect of the comparison between the top lipoprotein(a) tertile with the bottom lipoprotein(a) tertile (A) or the correlation coefficients (Pearson r) between lipoprotein(a) and Vpeak progression (B). ASTRONOMER indicates Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin; COR, correlation; PROGRESSA, Metabolic Determinants of the Progression of Aortic Stenosis; RoF, Ring of Fire; ROM, ratio of means; SALTIRE2, Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis.
Similar associations were observed when aortic stenosis progression was assessed using changes in mean pressure gradient. Patients in the top lipoprotein(a) tertile demonstrated a 57% faster progression of mean transvalvular gradient compared to patients in the bottom tertile (estimate, 1.57, 95% CI, 1.18-2.10) (Figure 2). When considered as a continuous variable, plasma lipoprotein(a) concentrations were again associated with mean gradient progression. In contrast, plasma lipoprotein(a) concentrations were not associated with annualized progression rates of the aortic valve area irrespective of whether plasma lipoprotein(a) concentrations were considered as tertiles or as a continuous variable (eFigure 1 in Supplement 1).
Figure 2. Association Between Exposure to Elevated Lipoprotein(a) Levels and Mean Transvalvular Gradients Progression in Patients From 5 Cohorts.
Effect sizes and meta-analysis represent the effect of the comparison between the top lipoprotein(a) tertile with the bottom lipoprotein(a) tertile (A) or the correlation coefficients (Pearson r) between lipoprotein(a) and mean transvalvular gradients progression (B). ASTRONOMER indicates Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin; COR, correlation; PROGRESSA, Metabolic Determinants of the Progression of Aortic Stenosis; RoF, Ring of Fire; ROM, ratio of means; SALTIRE2, Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis.
Results From the Individual Cohorts
Consistent with the results of the meta-analysis, patients in the top lipoprotein(a) tertile demonstrated an observed trend to faster progression in aortic jet velocity (Figure 3) compared to the bottom tertile in each study cohort except for PROGRESSA. However, the association was only statistically significant in ASTRONOMER. Similar associations were seen for annualized progression of mean pressure gradient in every cohort (except SALTIRE, which had no data available; Figure 4), although the association was only statistically significant in ASTRONOMER. There were no significant associations between lipoprotein(a) levels and annualized progression rates of the aortic valve area in each cohort (eFigure 2 in Supplement 1). Similar findings were seen for associations of plasma lipoprotein(a) concentrations when expressed as a continuous variable (eTable 6 in Supplement 1).
Figure 3. Annualized Peak Aortic Jet Velocity (Vpeak) Progression Rates in Patients From 5 Cohorts by Lipoprotein(a) Tertile.
Annualized peak aortic jet velocity in m/s/y in patients with aortic stenosis separated into lipoprotein(a) tertiles are reported as mean (SD) changes. ASTRONOMER indicates Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin; PROGRESSA, Metabolic Determinants of the Progression of Aortic Stenosis; SALTIRE, Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression; SALTIRE2, Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis.
Figure 4. Annualized Mean Transvalvular Gradients Progression Rates in Patients From 4 Cohorts by Lipoprotein(a) Tertiles.
Annualized mean transvalvular gradients in mm Hg/y in patients with aortic stenosis separated into lipoprotein(a) tertiles are reported as mean (SD) changes. ASTRONOMER indicates Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin; PROGRESSA, Metabolic Determinants of the Progression of Aortic Stenosis; SALTIRE2, Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis.
Discussion
In this meta-analysis of 710 patients with aortic stenosis from 5 longitudinal studies, those with higher lipoprotein(a) concentrations demonstrated a 41% faster progression in their aortic jet velocity and 57% faster progression in their mean transvalvular pressure gradient comparing top to bottom tertiles. This was supported by further analysis treating lipoprotein(a) as a continuous variable and the results did not demonstrate heterogeneity across the individual cohorts. These data would suggest lipoprotein(a) is associated not only with incident aortic stenosis, but also with progression of aortic stenosis. Lipoprotein(a) therefore represents an important potential therapeutic target in aortic stenosis.
Aortic stenosis is one of the last remaining cardiovascular conditions without an effective medical therapy. Large genetic studies have demonstrated the association between incident aortic stenosis and lipoprotein(a) concentrations across diverse patient cohorts.3,4,16 However, to be an important therapeutic target, lipoprotein(a) should also be associated with aortic stenosis disease progression and in particular hemodynamic progression assessed with echocardiography, the imaging test used in routine clinical practice to monitor aortic stenosis severity. Results from previous studies have been encouraging but limited by small sample sizes. A recent meta-analysis by Pantelidis et al17 revealed that patients with high lipoprotein(a) concentrations had faster aortic stenosis progression. However, these investigators did not have individual pooled patient-level data and only included data from 349 patients. Our study involves double the number of patients, extending their findings by adding the results of 2 new cohorts from the PROGRESSA and SALTIRE2 trials. In total, we have therefore performed a combined analysis of 5 different studies, including more than 700 patients from Europe and North America, making ours the largest reported study to our knowledge to document the association between hemodynamic aortic stenosis progression and lipoprotein(a) concentrations.
We observed an association between lipoprotein(a) concentrations and hemodynamic aortic stenosis progression using both the peak velocity and mean gradient. Previous studies have demonstrated that these echocardiographic measurements demonstrate the best precision of the echocardiographic assessments ensuring that they provide the greatest sensitivity in detecting disease progression.18,19 In contrast, we did not observe an association between lipoprotein(a) concentrations and change in aortic valve area. Calculation of the aortic valve area is based upon multiple Doppler measurements both before and after the aortic valve as well as measurements of the left ventricular outflow tract diameter. Aortic valve area is therefore marked by inferior precision compared to peak velocity and mean gradient, which translates into an inferior ability to detect small change in hemodynamic progression with time or in response to therapy.20 This likely explains the results observed here in this study and suggests the peak velocity and mean gradient hold advantages as efficacy end points in trials investigating the ability of novel therapies to slow hemodynamic aortic stenosis progression.
In the absence of an effective pharmacological therapy for aortic stenosis, and on the basis of our results presented here, we believe that large-scale randomized clinical trials should be performed to investigate whether the association between lipoprotein(a) and aortic stenosis progression is causal and whether lipoprotein(a)-lowering therapies could influence aortic stenosis progression.
In totality, we believe that these findings could inform the design of lipoprotein(a)-lowering trials in aortic stenosis, helping with power calculations for such trials and in selecting patient populations and relevant end points. In this regard, the Lp(a)FRONTIERS CAVS trial will test the hypothesis that lipoprotein(a) lowering with the antisense oligonucleotide against lipoprotein(a) pelacarsen will reduce aortic stenosis progression. This placebo-controlled trial will document the impact of pelacarsen vs matching placebo on aortic stenosis progression assessed by peak aortic jet velocity measured by echocardiography and aortic valve calcium measured by CT in approximately 500 patients with aortic stenosis. In this trial, a threshold value for lipoprotein(a) concentrations of 175 nmol/L has been selected. This threshold is higher than the top tertiles of all studies included in this analysis: 3-fold higher than the top tertiles in the PROGRESSA (51.3 nmol/L) and SALTIRE2 (42.1 nmol/L) studies (the only studies included in our analysis with lipoprotein(a) concentrations measured in nmol/L), double that in SALTIRE (29.0 mg/dL [approximately 72.5 nmol/L]) but only slightly higher than in the ASTRONOMER (58.4 mg/dL [approximately 146.0 nmol/L]) and Ring of Fire (50.4 mg/dL [approximately 126.0 nmol/L]) studies. Whether lipoprotein(a)-lowering therapies could influence aortic stenosis progression in patients with lower lipoprotein(a) concentrations than in Lp(a)FRONTIERS CAVS could be explored in future studies.
Limitations
These findings should be interpreted in the context of the study’s limitations. First, plasma lipoprotein(a) levels were measured using different assays that do not all report values in the same units, thereby limiting the interpretability of the effect sizes of the meta-analyses. Aortic stenosis progression could not be assessed across the full range of lipoprotein(a) concentrations. The limited number of patients in each cohort did not allow us to investigate the impact of lipoprotein(a) concentrations on aortic stenosis progression according to baseline severity of aortic stenosis, sex, or age. The aim of this study was to investigate the relationship between lipoprotein(a) concentrations and hemodynamic aortic stenosis progression on echocardiography. The cohorts were selected on this basis. Anatomic progression of aortic stenosis was not assessed. Future studies will investigate lipoprotein(a) concentrations and anatomic aortic stenosis progression with CT calcium scoring and will be based on the optimum cohorts available to address that particular question.
Conclusion
In conclusion, elevated lipoprotein(a) concentrations in this study were associated with more rapid hemodynamic aortic stenosis progression as assessed by the peak velocity and mean gradient. Further studies are warranted to assess whether this association is causal and whether lipoprotein(a) lowering might delay aortic stenosis progression in patients with elevated baseline concentrations.
eFigure 1. Association between exposure to elevated lipoprotein(a) levels and aortic valve area progression in patients from five cohorts. Effect sizes and meta-analysis represent the effect of the comparison between the top lipoprotein(a) tertile with the bottom lipoprotein(a) tertile (A) or the correlation coefficients between lipoprotein(a) and aortic valve area progression (B).
eFigure 2. Annualized aortic valve area progression rates in patients from five cohorts (A) ASTRONOMER, B) PROGRESSA, C) Ring of Fire, D) SALTIRE 1 and E) SALTIRE) separated into lipoprotein(a) tertiles.
eTable 1. Baseline characteristics of ASTRONOMER study participants separated into lipoprotein(a) tertiles.
eTable 2. Baseline characteristics of PROGRESSA study participants separated into lipoprotein(a) tertiles.
eTable 3. Baseline characteristics of Ring of Fire study participants separated into lipoprotein(a) tertiles.
eTable 4. Baseline characteristics of SALTIRE study participants separated into lipoprotein(a) tertiles.
eTable 5. Baseline characteristics of SALTIRE2 study participants separated into lipoprotein(a) tertiles.
eTable 6. Impact of lipoprotein(a) expressed as a continuous variable on hemodynamic and anatomical aortic stenosis progression in the five cohorts.
Data sharing statement
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eFigure 1. Association between exposure to elevated lipoprotein(a) levels and aortic valve area progression in patients from five cohorts. Effect sizes and meta-analysis represent the effect of the comparison between the top lipoprotein(a) tertile with the bottom lipoprotein(a) tertile (A) or the correlation coefficients between lipoprotein(a) and aortic valve area progression (B).
eFigure 2. Annualized aortic valve area progression rates in patients from five cohorts (A) ASTRONOMER, B) PROGRESSA, C) Ring of Fire, D) SALTIRE 1 and E) SALTIRE) separated into lipoprotein(a) tertiles.
eTable 1. Baseline characteristics of ASTRONOMER study participants separated into lipoprotein(a) tertiles.
eTable 2. Baseline characteristics of PROGRESSA study participants separated into lipoprotein(a) tertiles.
eTable 3. Baseline characteristics of Ring of Fire study participants separated into lipoprotein(a) tertiles.
eTable 4. Baseline characteristics of SALTIRE study participants separated into lipoprotein(a) tertiles.
eTable 5. Baseline characteristics of SALTIRE2 study participants separated into lipoprotein(a) tertiles.
eTable 6. Impact of lipoprotein(a) expressed as a continuous variable on hemodynamic and anatomical aortic stenosis progression in the five cohorts.
Data sharing statement