Assessment of the Utilization of Lipoprotein (a) and its Relationship with Cardiovascular Outcomes: A Retrospective Cohort Study from a Public Hospital in New York City

Abstract

Introduction:

Lipoprotein (a) [Lp(a)] is an independent genetic risk factor for atherosclerotic cardiovascular disease (ASCVD) and is associated with an increased risk of heart failure (HF), multiple vascular and valvular abnormalities and is closely linked to various lipid components, particularly low-density lipoprotein (LDL) cholesterol. Despite its clinical significance, Lp(a) testing has not gained widespread use in healthcare practice. Our study aimed to assess the utilization of Lp(a) testing and its association with ASCVD risk factors, HF phenotypes, vascular and valvular pathologies, lipid profiles, and the use of lipid-lowering drugs at a safety-net hospital within the largest municipal healthcare system in the United States.

Methods:

We conducted a retrospective study at Jacobi Medical Center, a public hospital in the Bronx, New York. Using a cutoff value of 75 nmol/L, we compared a study group with elevated Lp(a) levels to a control group. The primary outcomes assessed were the association between Lp(a) levels and ASCVD risk factors, HF phenotypes (classified by left ventricular ejection fraction), and vascular and valvular pathologies. Secondary outcomes included the relationship between elevated Lp(a) levels and lipid profiles, as well as the use of lipid-lowering medications such as statins, proprotein convertase subtilisin/kexin type 9 inhibitors, and ezetimibe.

Results:

The study included 78 patients (41.0% female, median age 52.0 years, interquartile range 44.0–66.0 years). Patients with elevated Lp(a) had a significantly higher incidence of HF with preserved ejection fraction (HFpEF) (18.8% vs. 0%, P = 0.004), but there was no significant association with HF with reduced ejection fraction (15.6% vs. 36.3%, P = 0.613) or HF with midrange ejection fraction (12.5% vs. 13.6%, P = 0.061). No significant associations were found between elevated Lp(a) and ASCVD risk factors, or valvular and vascular pathologies. However, patients with high Lp(a) levels had significantly higher LDL levels (96.5 mg/dL vs. 73.0 mg/dL, P = 0.04). There was no significant association between the use of lipid-lowering drugs and elevated Lp(a) levels. Notably, some patients exhibited unexpectedly high Lp(a) levels despite having a comparable demographic and comorbidity risk profile to those with normal Lp(a) levels.

Conclusion:

Patients with elevated Lp(a) levels were more likely to present with HFpEF and elevated LDL levels, although no significant associations were found with ASCVD risk factors, vascular, or valvular pathologies. The unexpectedly high Lp(a) levels in some individuals with similar risk profiles suggest the need for further research to refine guidelines for Lp(a) testing. Our study also highlighted the underutilization of Lp(a) testing in clinical practice, underscoring the importance of increasing awareness and improving ASCVD risk assessment strategies.

INTRODUCTION

Lipoprotein (a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle that includes a large glycoprotein called apolipoprotein (a) [apo (a)], which is covalently bonded to apolipoprotein B-100, a key protein in cholesterol and lipid transport.[1,2] Lp(a) levels, primarily determined by genetics, range widely from <1 to over 200 mg/dL in the general population.[3] Epidemiological research, meta-analyses, genome-wide association studies, and Mendelian randomization have all established Lp(a) as a genetically inherited and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Elevated Lp(a) levels are present in approximately 20% of the global population, making it a significant contributor to cardiovascular risk worldwide.[3,4,5,6] In addition, elevated levels of Lp(a) have been linked to an increased risk of heart failure (HF), valvular and vascular diseases, particularly aortic stenosis (AS) and aortic valve calcification, as well as higher levels of LDL cholesterol.[7,8,9]

ASCVD is a major cause of morbidity and mortality worldwide, affecting over 500 million individuals globally and resulting in approximately 19 million deaths each year.[10,11,12,13] In the United States of America (USA), it affects around 26 million people, leading to 2 million hospitalizations and 400,000 deaths per year.[14,15] The annual economic burden of ASCVD in the USA is estimated at approximately $239.9 billion.[15] Further, approximately 5.7 million adults have HF, with estimated annual direct costs ranging from $39.2 billion to $60 billion.[16] In addition, valvular and vascular pathologies represent a significant economic burden; for instance, peripheral arterial disease (PAD) incurs costs of $16,752 per patient.[17] Hence, prioritizing the prevention of ASCVD, HF, and vascular and valvular pathologies through efficient risk assessment and management is a public health priority where Lp(a) can play a pivotal role.

There is no consensus on the Lp(a) risk thresholds. The American College of Cardiology/American Heart Association (ACC/AHA), Canadian Cardiovascular Society, National Lipid Association, American Association of Clinical Endocrinologists, and American College of Endocrinology consider values above 50 mg/dL or 125 nmol/L to be high and associated with an increased risk of ASCVD.[18,19,20,21] In contrast, the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) consider levels above 30 mg/dL or 75 nmol/L to be elevated.[22] However, laboratories in both Europe and the USA using the various industry standard immunoassays available, such as enzyme-linked immunosorbent assay (ELISA), electrophoresis, and immunodiffusion, report Lp(a) levels above 30 mg/dl or 75 nmol/L as elevated.[23,24,25] In line with the above, we have defined Lp(a) >75 nmol/L as elevated in our study. Despite the lack of consensus on specific Lp(a) thresholds, most guidelines, including the 2022 EAS and 2019 ESC/EAS, recommend measuring Lp(a) at least once in a lifetime for all adults, regardless of the presence or absence of ASCVD risk factors.[26,27] In addition, the 2019 ACC/AHA guidelines suggest Lp(a) testing for individuals with a family history of premature ASCVD.[28] However, despite the association of Lp(a) and ASCVD, its measurement has not gained widespread acceptance in clinical practice.[29]

The aim of this study was to evaluate the utilization of Lp(a) (>75 nmol/L) and its association with ASCVD risk factors, HF and its phenotypes, vascular and valvular pathologies, lipid profiles, and the use of lipid-lowering drugs in patients receiving care at a safety-net public hospital in New York City.

MATERIALS AND METHODS

Study design, study setting, and patient population

We conducted a retrospective study of patients admitted to Jacobi Medical Center, a public hospital within the New York City Health + Hospitals (NYC H + H) system, who had a documented serum Lp(a) level between August 01, 2020 and September 30, 2023. Each year, nearly one million people receive care through the NYC H + H system, with the majority being from low-income backgrounds or ethnically marginalized communities. Of these patients, 32% are uninsured, 35% are covered by Medicaid, and 70% are people of color.[30] All patients ≥18 years of age seen in the inpatient and/or outpatient settings at Jacobi Medical Center with a documented serum Lp(a) level between August 01, 2020, and September 30, 2023, were included in the study. Patients who met any of the following criteria were excluded from the study: (i) pregnant women, (ii) prisoners, (iii) patients <18 years old, and (iv) patients without a recent transthoracic echocardiogram or transesophageal echocardiogram result dating from the last Lp(a) measurement. This study was approved by the Institutional Review Board (IRB) of the Biomedical Research Alliance of New York on 9/14/23 with a waiver of informed consent (IRB# 23-12-594-71). It was conducted in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for observational studies as included in Supplement 1 ^{(453.3KB, pdf)} .[31]

Data sources

The EPIC (Epic Systems, Verona, WI, USA) electronic medical record (EMR) was used for data search and extraction.[32] The data were collected using Slicer Dicer tool available in EPIC, followed by a retrospective examination of patient charts by four separate researchers (MM, NN, PB, VG) who worked independently and were blinded to each other.[33] Discrepancies were resolved by reaching a consensus among the four researchers, and data were anonymized before extraction.

Patients were stratified into two cohorts according to their Lp(a) concentrations: the study group with elevated Lp(a) (>75 nmol/L) and the control group with Lp(a) levels within the normal range (<75 nmol/L). Throughout the study period, all Lp(a) laboratory tests were conducted at commercial laboratories using ELISA assays that adhere to industry standards.

Data were abstracted for patient characteristics, ASCVD risk factors, HF and its phenotypes, valvular and vascular pathologies, lipid profile, and use of lipid-lowering drugs. Baseline patient characteristics included age, sex, race and/or ethnicity, and body mass index (BMI). ASCVD-related risk factors encompassed a history of diabetes mellitus (DM), hyperlipidemia (HLD), hypertension (HTN), current smoking, and homocysteine levels. HF and its phenotypes were categorized based on left ventricular ejection fraction (LVEF) into HF with reduced LVEF (HFrEF) with LVEF < 40%, HF with mid-range EF (HFmrEF) with LVEF 40%–49%, and HF with preserved EF (HFpEF) with LVEF ≥ 50%. Data on valvular and vascular pathologies included PAD, aneurysms of major vessels such as the ascending thoracic aorta and abdominal aorta, ascending thoracic aorta calcifications, abdominal aortic calcifications, aortic valve calcifications, mitral annular calcification (MAC), and AS. Lipid profile data included levels of LDL and high-density lipoprotein (HDL), along with the use of pharmacological agents such as statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and ezetimibe. None of the patients were on newer therapies, such as antisense oligonucleotides and small interfering RNA. Patients on statin therapy were further categorized into moderate intensity (equivalent to atorvastatin 10–20 mg, rosuvastatin 5–10 mg, and simvastatin 20–40 mg) and high intensity (equivalent to atorvastatin 40–80 mg and rosuvastatin 20–40 mg) based on the ACC/AHA classification of statin dosing intensity.[34]

Exposure of interest and outcomes

This retrospective study compared the demographics of normal (<75 nmol/L) and elevated levels of Lp(a) (>75 nmol/L) in our hospital’s diverse patient population. The primary outcome of interest was the association between Lp(a) levels and ASCVD risk factors, HF and its phenotypes, and vascular and valvular pathologies. The secondary outcome was to determine the relationship between elevated Lp(a) levels and lipid profiles, as well as the use of lipid-lowering therapies, including statins, PCSK9 inhibitors, and ezetimibe.

Statistical analysis

The cohort was divided based on Lp(a) values: control group with normal Lp(a) levels (<75 nmol/L) and study group with elevated levels (>75 nmol/L). The t-test was used to compare continuous variables, and Chi-square or Fisher’s exact test was used for discrete variables. Continuous data were presented as median with interquartile range (IQR) and categorical data as absolute and relative frequencies.

The threshold of statistical significance was P < 0.05. All analyses were performed using STATA software (version 16.1; STATA Corporation, College Station, TX, USA).[35]

Graphical abstract

RESULTS

Patient demographics

Seventy-eight patients were included (41.0% female, median age IQR 52.0 [44.0–66.0] years) with a median [IQR] BMI of 29.9 [26.4–37.1] kg/m². Thirty-two/78 patients had raised Lp(a) levels (>75 nmol/L), with a median of 143.3 nmol/L. The prevalence of elevated Lp(a) (>75 nmol/L) was higher among African Americans (41.9%), followed by Hispanics (25.8%), and lowest among Whites (6.5%). These findings are summarized in Table 1.

Table 1.

Demographics and association with lipoprotein (a) levels

Demographics	Total	Lp(a) <75 nmol/L (n=46)	Lp(a) >75 nmol/L (n=32)	P
Sex, n (%)
Female	32 (41.0)	18 (39.1)	14 (43.7)	0.68
Male	46 (58.9)	28 (60.8)	18 (56.3)
Age (years), median (IQR)	52.0 (44.0–62.0)	50.0 (42.0–63.0)	53.5 (44.0–60.5)	0.36
Age groups (years), n (%)
≤60	53 (67.95)	30 (65.22)	23 (71.88)	0.137
60–75	23 (29.49)	16 (34.78)	7 (21.88)
>75	2 (2.56)	0	2 (6.25)
BMI (kg/m2), median (IQR)	29.9 (26.4–37.1)	30.3 (27.2–37.0)	29.3 (25.2–37.7)	0.45
Obese, n (%)	38 (48.7)	26 (56.5)	12 (37.5)	0.09
Race and/or ethnicity, n (%)
White	6 (7.7)	4 (8.7)	2 (6.4)	0.32
African American	22 (28.5)	9 (19.5)	13 (41.9)
Hispanic	27 (35.0)	19 (41.3)	8 (25.8)
Asian	10 (12.9)	6 (13.0)	4 (12.9)
Other	12 (15.5)	8 (17.3)	4 (12.9)

IQR: Interquartile range, BMI: Body mass index, n: Number of patients, LP: Lipoprotein

Primary outcome: Association of lipoprotein (a) and atherosclerotic cardiovascular disease-associated risk factors, heart failure and its phenotypes, vascular and valvular pathologies

No significant association was found between elevated Lp(a) levels and ASCVD risk factors. Individuals with increased Lp(a) levels were noted to have a numerically lower prevalence of smoking (28.1% vs. 44.4%; P = 0.14), type 2 DM (28.1% vs. 34.7%; P = 0.82), and HLD (68.7% vs. 73.9%; P = 0.61), and a higher prevalence of HTN (81.2% vs. 65.2%; P = 0.12) and type 1 DM (type 1 DM) (12.5% vs. 10.8%; P = 0.82) compared to those with normal Lp(a) levels. In addition, the homocysteine levels, measured in 4/78 individuals in the study, were higher in the elevated Lp(a) group (11.7 micromoles per liter (mcmol/L) vs. 10 mcmol/L; P = 0.65). The results are illustrated in Table 2.

Table 2.

Association of lipoprotein (a) levels with atherosclerotic cardiovascular disease risk factors

ASCVD risk factors	Total	Lp(a) <75 nmol/L	Lp(a) >75 nmol/L	P
Current smoking, n (%)	29 (37.6)	20 (44.4)	9 (28.1)	0.14
DM, n (%)
Type 1	9 (11.5)	5 (10.8)	4 (12.5)	0.82
Type 2	25 (32.0)	16 (34.7)	9 (28.1)
HTN, n (%)	56 (71.7)	30 (65.2)	26 (81.2)	0.12
HLD, n (%)	56 (71.7)	34 (73.9)	22 (68.7)	0.61
Homocysteine levels (μmol/L), median (IQR)	10.8 (9.3–11.8)	10.0 (10.0–10.0)	11.7 (8.7–12.0)	0.65

IQR: Interquartile range, ASCVD: Atherosclerotic cardiovascular disease, DM: Diabetes mellitus, HTN: Hypertension, HLD: Hyperlipidemia, n: Number of patients, LP: Lipoprotein

Evaluating HF and its phenotypes based on LVEF, in the subset of individuals with elevated Lp(a) levels (>75 nmol/L), the prevalence of HFpEF was significantly higher compared to that of HFrEF and HFmrEF (18.7% vs. 15.6% vs. 12.5%; P = 0.004). The key findings are detailed in Table 3.

Table 3.

Association of lipoprotein (a) levels with heart failure and its phenotypes based on left ventricular ejection fraction

HF and its phenotypes	Total	Lp(a) <75	Lp(a) >75	P
HF, n (%)				0.008
HFrEF (EF <41%)	21 (27.6)	16 (36.3)	5 (15.6)	0.061
HFmrEF (EF 41%–49%)	10 (13.1)	6 (13.6)	4 (12.5)	0.613
HFpEF (EF >50%)	6 (7.8)	0	6 (18.7)	0.004

n: Number of patients, HF: Heart failure, HFrEF: Heart failure with reduced ejection fraction, EF: Ejection fraction, HFmrEF: Heart failure with mid-range ejection fraction, HFpEF: Heart failure with preserved ejection fraction, LP: Lipoprotein

In respect to vascular and valvular pathologies, no significant associations were found with elevated Lp(a) levels. Although the association lacked statistical significance, the incidence of PAD (3.1% vs. 4.3%; P = 0.78) was numerically lower in the cohort with high Lp(a). In addition, in individuals with elevated Lp(a), there was a higher incidence of aortic valve calcification (15.6% vs. 8.7%; P = 0.47), MAC (25.0% vs. 19.5%; P = 0.56), ascending thoracic aortic calcification (10.0% vs. 6.6%; P = 0.76), and lower incidence of abdominal aortic calcification (0% vs. 20.0%; P = 0.54). None of the patients in this study had diagnosed aneurysms of the abdominal and thoracic aorta and AS. The results are summarized in Table 4.

Table 4.

Association of lipoprotein (a) levels with vascular and valvular pathologies

Vascular and valvular pathologies	Total	Lp(a) <75 nmol/L	Lp(a) >75 nmol/L	P
PAD, n (%)	3 (3.8)	2 (4.3)	1 (3.1)	0.78
Calcifications of aortic valves on TTE/TEE, n (%)	9 (11.5)	4 (8.7)	5 (15.6)	0.47
Calcifications of mitral valves on TTE/TEE, n (%)	17 (21.7)	9 (19.5)	8 (25.0)	0.56
Abdominal aorta calcifications on CT abdomen, n (%)	4 (15.3)	4 (20.0)	0	0.54
Ascending thoracic aortic calcifications on CT chest, n (%)	2 (8.0)	1 (6.6)	1 (10.0)	0.76

PAD: Peripheral arterial disease, TTE: Transthoracic echocardiogram, TEE: Transesophageal echocardiogram, CT: Computed tomography, n: Number of patients, LP: Lipoprotein

Secondary outcome: Association of lipoprotein (a) and lipid levels and lipid-lowering drugs

Elevated Lp(a) levels were significantly associated with elevated LDL levels (96.5.0 mg/dL vs. 73.0 mg/dL, P = 0.04), whereas no significant relationship was observed with increased HDL levels. There were no statistically significant differences in the use of high-intensity statins (54.8% vs. 54.3%; P = 0.69), PCSK9 inhibitors (12.5% vs. 8.7%; P = 0.71), and ezetimibe (18.7% vs. 21.7%; P = 0.78) between elevated Lp(a) and the normal Lp(a) cohorts. These findings are summarized in Table 5.

Table 5.

Association of lipoprotein (a) levels with lipid levels and use of lipid-lowering drugs

Lipid levels and lipid -lowering drugs	Total	Lp(a) <75 nmol/L	Lp(a) >75 nmol/L	P
LDL (mg/dL), median (IQR)	86.0 (61.9–126.0)	73.0 (51.8–108.0)	96.5 (71.3–140.4)	0.04
HDL (mg/dL), median (IQR)	42.5 (35.0–53.0)	40.5 (33.0–52.0)	46.0 (37.5–53.5)	0.12
Statin use, n (%)
Moderate intensity	22 (28.5)	12 (26.0)	10 (32.2)	0.69
High intensity	42 (54.5)	25 (54.3)	17 (54.8)
PCSK9 inhibitor use, n (%)	8 (10.2)	4 (8.7)	4 (12.5)	0.71
Ezetimibe use, n (%)	16 (20.5)	10 (21.7)	6 (18.7)	0.78

IQR: Interquartile range, LDL: Low-density lipoprotein, HDL: High-density lipoprotein, PCKS9: Proprotein convertase subtilisin/kexin type, n: Number of patients, LP: Lipoprotein

DISCUSSION

In our cohort of 78 patients with normal versus elevated Lp(a) levels, we found no significant differences in their baseline characteristics, comorbidities, valvular pathologies., and use of lipid lowering drugs. Patients with elevated Lp(a) were found to have a higher prevalence of HFpEF and higher LDL levels. Through these results, we aim to provide insight into the widely diverse demographic population of a large New York City public hospital and highlight that Lp(a) levels may be abnormally high in certain patients despite having the same baseline profile as their counterparts with a normal Lp(a). This opens the scope and discussion for larger studies to establish better guidelines for Lp(a) testing.

The association of Lp(a) with cardiovascular disease (CVD) has been demonstrated in multiple studies. A Danish study conducted in 2007 with nearly 10,000 participants found that Lp(a) levels exceeding 258 nmol/L increase the risk of myocardial infarction by 35% in females and 20% in males.[36] In addition, the JUPITER study (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) showed that elevated Lp(a) levels were associated with residual CVD risk even after being on optimal medical treatment including high-intensity statins (P = 0.02).[37] However, in their study of 26,000 healthy patients, Mora et al. showed an inverse relation of Lp(a) with diabetes in the absence of CVD.[38] While there are clear associations of elevated Lp(a) with worse CVD outcomes such as coronary artery disease and the ACC/AHA guidelines recommend testing for Lp(a) at least once in a lifetime, it is unclear solely based on demographics and comorbidities which patients should get Lp(a) tested.[39,40,41,42] Our study showed a very similar profile in terms of the equal prevalence of diabetes, HTN, HLD, smoking, homocysteine levels, valvular calcifications, HFrEF, and the use of lipid lowering drugs between both groups. Despite this, elevated Lp(a) levels were found in 46 patients. Furthermore, the LPA gene polymorphism contributes significantly to elevated Lp(a) levels, especially in Asian populations.[43] Due to our limited power, we were not able to show that association, however, we found that other ethnic groups including African Americans might also be at a similarly higher risk.[44,45]

In terms of Lp(a)’s association with LDL, our findings are in line with those of previous studies. In the Women’s Health Study by Suk Danik et al., encompassing 27,791 women with 899 incident cardiovascular events, there was a significant interaction between elevated Lp(a) levels (>95 nmol/L) and high LDL levels (>3.1 mmol/L) with ASCVD in women.[46] Further, in the Prospective Cardiovascular Münster (PROCAM) study, which included data from 788 participants experiencing 44 cardiovascular events, Lp(a)(>43 nmol/L) emerged as a predictor of cardiovascular events, particularly in instances of higher LDL levels (>4.1 mmol/L).[47] In addition, our study includes a patient population that is racially more diverse compared to Suk Danik et al., which primarily included White patients (94.4%).[46] However, our study does not report the duration of use of statins and ezetimibe, which selectively lower LDL without affecting Lp(a), and PCSK9 inhibitors, which have a significant lowering effect on Lp(a) by 20%–25%.[48,49,50] Importantly, Lp(a) and LDL levels were not compared before and after the use of lipid-lowering drugs. Furthermore, although not statistically significant, there was a higher percentage of use of statin and PCKS9 inhibitor in the elevated Lp(a) cohort which might have affected the levels of LDL and Lp(a) levels. Therefore, the effects of these drugs on Lp(a) levels and the association of Lp(a) with LDL, as reported in our study, should be interpreted with caution.

Our study analyzed the association of Lp(a) with HF and its phenotypes, wherein elevated Lp(a) was significantly associated with the presence of HFpEF. Previously, in a study of 98,907 Danish patients, elevated levels of Lp(a) were associated with a higher risk of developing HF (Hazard ratio (HR): 1.18; 95% confidence interval: 1.04–1.34).[9] Similarly, in a retrospective study of 6,089 patients by Steffen et al., elevated levels of Lp(a) (>75 nmol/L) were linked to an increased risk of HFpEF (P = 0.01) among White patients but not among other races.[51] Importantly, our study found a significant association uniformly across all analyzed races and ethnicities, underscoring the importance of Lp(a) testing for HFpEF in a more racially diverse population. Chehab et al. found the association between elevated Lp(a) levels and myocardial scarring and cardiac remodeling, which contribute to an increased afterload and may raise the risk of developing HFpEF.[52] Future research confirming the association between elevated Lp(a) levels and HFpEF in a larger study population and exploring the underlying pathophysiologic changes is required for a deeper understanding.

Our study also highlighted the underutilization and lack of awareness regarding the importance of Lp(a) testing, with only 78 patients undergoing the test. A study by Bhatia et al. revealed similar findings, involving over 5.5 million adults across multiple academic health systems in California from 2013 to 2021, where only 0.3% of the population underwent Lp(a) testing.[53] Similarly, McGowan et al. and Kelsey et al. reported low rates of Lp(a) testing, with only 0.06% to 3% of individuals being tested.[54,55] In addition, a survey conducted by the University of Pennsylvania Health System involving 126 providers found that around 75% of them did not test their patients for Lp(a).[56]

Fonseca et al. demonstrated that Lp(a) testing in clinical practice led to the early initiation of statin or other lipid-lowering therapies, a trend mirrored in our study, where a higher proportion of individuals with elevated Lp(a) levels were prescribed moderate (32.3%) and high-intensity statins (54.8%) and PCSK9 inhibitors (12.5%).[57] These results emphasize the vital importance of early identification of high-risk patients through Lp(a) testing, implementing risk-modifying behaviors, and mitigating the economic strain of ASCVD on the US healthcare system. Our study highlights the limited use of Lp(a) testing in a public city hospital and encourages physicians across all specialties to reflect on and increase their utilization of Lp(a). There is a growing need to raise awareness of its clinical value, particularly in populations with multiple comorbidities, where its efficacy could significantly impact cardiovascular outcomes.

Strengths and limitations

There are several strengths and limitations to this study. Importantly, this study analyzed the baseline characteristics, ASCVD risk factors, HF, various vascular and valvular pathologies, and lipid profile among patients with raised Lp(a) treated at a safety net tertiary hospital within the largest municipal healthcare system in the USA. One of the key strengths is the included underserved population, which represents a socioeconomically disadvantaged cohort with multiple comorbidities, in whom Lp(a) testing can help with accurate ASCVD risk assessment and help reduce cardiovascular morbidity and mortality. Despite these strengths, considering the small sample size, we recognize that the study may have been underpowered to detect significant differences in cardiovascular outcomes in patients with elevated Lp(a) and the results should be interpreted with caution. In addition, being a single-center study, our findings cannot be easily generalized. Further, the duration of use of statins and other lipid-lowering drugs was not accounted for, which may have affected the association of Lp(a) with the measured lipid components. Due to the retrospective nature of this study, we could not follow patients with Lp(a) to determine the incidence of MACE and CV mortality, which would have given further insight on the association of Lp(a) with ASCVD outcomes. Although this was a real-world study, its retrospective design, relying on EMRs, is less ideal compared to a prospective design, which would enable a more precise and comprehensive follow-up assessment.

CONCLUSIONS

While patients with elevated Lp(a) levels were more likely to have HFpEF and elevated LDL levels, our study demonstrates that Lp(a) levels can be unusually elevated in some patients, even when they have a similar demographic and comorbidity risk profile to those with normal Lp(a) levels. The limited size of our retrospective cohort significantly restricts the generalizability but highlights the underutilization of Lp(a) in clinical settings and the lack of awareness regarding its significance in ASCVD. This emphasizes the need for increased awareness and utilization of Lp(a) levels in clinical practice to effectively assess ASCVD risk, particularly in diverse populations with complex comorbidity burden profile. Further research involving larger, more diverse cohorts, with extended follow-up periods and consideration of confounding factors such as the use of lipid-modifying drugs, is needed to better assess the association between Lp(a) and cardiovascular outcomes in populations with multiple comorbidities.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.