Abstract
Background
Lipoprotein(a) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, its distribution based on coronary artery disease (CAD) in the Japanese population remains unclear. We compared lipoprotein(a) distributions among patients with acute coronary syndrome (ACS), patients with chronic coronary syndrome (CCS), and controls.
Methods and Results
We analyzed 3,710 individuals who visited Kagawa Prefectural Central Hospital from April 2019 to March 2024. Patients who underwent percutaneous coronary intervention (PCI) were classified into ACS (n=724) and CCS (n=579) groups. Another 2,407 individuals without ASCVD undergoing medical check-ups were the controls. Lipoprotein(a) levels were measured before PCI or during check-up. Distributions and associations with prevalent CAD were assessed using multivariable logistic regression. The mean ages were 70, 72, and 56 years in the ACS, CCS, and control groups, respectively (P<0.001). Median lipoprotein(a) levels were 13, 14, and 10 mg/dL in the ACS, CCS, and control groups, respectively (P<0.001). Proportions of patients with lipoprotein(a) >30 mg/dL were 19.1% and 26% (P<0.05), and proportions of patients with lipoprotein(a) >50 mg/dL were 7.8% and 11.5% in the ACS and CSS groups, respectively (P<0.05). Restricted cubic splines suggested continuous associations between lipoprotein(a) and prevalent ACS and CCS. Statin use did not affect intergroup differences.
Conclusions
Lipoprotein(a) levels were higher in patients with CAD than in the controls, supporting its role as an independent risk marker.
Key Words: Acute coronary syndrome, Chronic coronary syndrome, Lipoprotein(a)
Central Figure.
Lipid-lowering therapy is a widely used pharmacologic approach for atherosclerotic cardiovascular disease (ASCVD). Intensive reduction of low-density lipoprotein cholesterol (LDL-C) using statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly decreases cardiovascular events.1–4 However, even with optimal LDL-C lowering, coronary artery disease (CAD), including acute coronary syndrome (ACS), remains a major cause of mortality and morbidity worldwide.5
Recent epidemiological and clinical studies have identified lipoprotein(a) as an independent risk factor for ASCVD.6,7 Lipoprotein(a) comprises an apolipoprotein-B-containing LDL-like particle covalently bound to a plasminogen-like glycoprotein, apolipoprotein(a).8 Plasma lipoprotein(a) levels are largely genetically determined by variations in the apolipoprotein(a) gene and remain stable throughout life except when influenced by environmental factors.9 Lipoprotein(a) can penetrate the arterial wall, bind to extracellular matrix components, and promote foam cell formation, smooth muscle cell proliferation, and inflammatory activation.10,11 Elevated lipoprotein(a) levels enhance atherosclerosis, thrombogenesis, and inflammation, thereby contributing to plaque formation and destabilization.12,13
Importantly, elevated lipoprotein(a) levels increase the risk of recurrent cardiovascular events independently of LDL-C concentration14 and are strongly associated with ASCVD.15–17 Consequently, current guidelines recommend measuring lipoprotein(a) to improve lifetime ASCVD risk stratification.18 Notably, circulating lipoprotein(a) levels vary by ethnicity and region, with East Asian populations generally exhibiting lower levels.19 Therefore, population-specific data are necessary for accurate interpretation and clinical assessment.
To clarify the distribution and clinical significance of lipoprotein(a) among different populations, this study aimed to evaluate and compare serum lipoprotein(a) levels in patients with ACS, patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI), and healthy individuals in a Japanese cohort.
Methods
Study Design and Population
This single-center, retrospective observational study was conducted at Kagawa Prefectural Central Hospital (KPCH). This study included 2 cohorts. The first cohort comprised patients who underwent PCI at KPCH between April 2019 and March 2024, including 804 patients with ACS and 1,284 with CCS. For patients undergoing multiple PCI procedures, only the initial event was considered, and subsequent events and individuals with unmeasured lipoprotein(a) were excluded. Consequently, 704 patients with ACS and 579 with CCS were included in the analysis. The second cohort comprised individuals who underwent medical check-ups at KPCH during the same period. For those who underwent multiple examinations, only the initial examination was considered. Individuals who did not consent to lipoprotein(a) measurement and those with a history of ASCVD were excluded. The history of ASCVD events was determined based on patient interviews. Ultimately, 2,407 individuals from the health examination cohort were included in the analysis as the control group. This study analyzed a combined total of 3,710 individuals in the 2 cohorts (Figure 1).
Figure 1.
Flowchart of participant selection. In total, 3,710 individuals were analyzed from April 2019 to March 2024. Patients who underwent percutaneous coronary intervention (PCI) were classified into the acute coronary syndrome (ACS; n=724) and chronic coronary syndrome (CCS; n=579) groups. Another 2,407 individuals without atherosclerotic cardiovascular disease (ASCVD) undergoing medical check-ups were included in the control group.
Ethical Considerations
This study was approved by the KPCH Ethics Committee. The requirement for informed consent was waived for the ACS and CCS groups owing to the study’s minimal risk and impracticality of obtaining consent from all patients. Instead, study details were disclosed within the hospital and on the KPCH website (http://www.chp-kagawa.jp/), allowing patients to opt out. Written informed consent was obtained from all participants in the medical check-up group. The study adhered to the principles of the Declaration of Helsinki.
In the ACS group, lipoprotein(a) levels were measured on the day of admission for suspected ACS, diagnosed according to the American College of Cardiology (ACC)/American Heart Association (AHA) 2007 guideline: recent-onset chest pain with ST-segment or T-wave electrocardiographic changes and/or elevated cardiac enzymes (creatine kinase or troponin T).20 In the CCS group, lipoprotein(a) levels were measured within 3 months before PCI, and CCS was diagnosed per the 2014 ACC/AHA guideline for stable ischemic heart disease.21 If a patient underwent multiple PCIs, only the first lipoprotein(a) value was used. Individuals in the control group with a history of cardiovascular disease were excluded.
Blood Sampling
Blood samples were collected in the emergency room, outpatient laboratory, or during medical check-up visits at KPCH. Plasma lipoprotein(a) levels were analyzed externally (SRL Inc., Tokyo, Japan) using the Sekisui assay kit, which uses monoclonal antibodies and a latex turbidimetric immunoassay. Results are expressed in milligrams per deciliter (mg/dL). Routine laboratory tests – including total cholesterol, fasting triglycerides, LDL-C, high-density lipoprotein cholesterol (HDL-C), hemoglobin A1c, and serum creatinine – were performed using an automated analyzer at KPCH. LDL-C was measured directly.
Assessment of Additional Risk Factors
Hypertension was defined according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2019.22 Diabetes was defined as a prior diagnosis recorded in medical files, hemoglobin A1c (National Glycohemoglobin Standardization Program) ≥6.5%, or ongoing treatment with oral antidiabetic agents or insulin. Dyslipidemia was determined following the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2017.23
Statistical Analysis
Continuous variables with normal distributions are reported as mean±standard deviation (SD); non-normally distributed variables are presented as median (interquartile range [IQR]). Categorical variables are expressed as frequencies and percentages (%). Differences in normally distributed continuous variables among the ACS, CCS, and control groups were analyzed using analysis of variance (ANOVA), and non-normally distributed variables were compared using non-parametric tests (Mann-Whitney U and Kruskal-Wallis). Categorical variables were evaluated using the chi-square test. The proportion of individuals with elevated lipoprotein(a) levels (≥30 mg/dL and ≥50 mg/dL) was compared among groups using the chi-square test, yielding odds ratios (ORs) and 95% confidence intervals (CIs). Associations between lipoprotein(a) and CAD risk were assessed using logistic regression models with log-transformed lipoprotein(a) as a continuous variable and restricted cubic spline terms. Covariates included age, sex, body mass index, chronic kidney disease, hypertension, diabetes, dyslipidemia, smoking (current, past, or never), and a history of myocardial infarction, stroke, or heart failure. The median in the lowest quartile was used as the reference, with knots at the 5th, 35th, 65th, and 95th percentiles of lipoprotein(a).
Subgroup analyses compared lipoprotein(a) levels across predefined categories: sex (male vs. female); age (<70 vs. ≥70 years); diabetes status; estimated glomerular filtration rate (eGFR >60 vs. <60 mL/min/1.73 m2); with or without prior statin therapy; and baseline LDL-C (<120 vs. ≥120 mg/dL). For multiple comparisons, the Bonferroni post hoc test was applied. A 2-tailed P value <0.05 was considered statistically significant. Statistical analyses were conducted using SPSS version 27.0 (IBM, Armonk, NY, USA) and R version 4.4.2 (The R Foundation for Statistical Computing, Vienna, Austria).
Results
Table 1 presents the baseline characteristics of the study population. The control group included individuals with no history of cardiovascular events, and their clinical profiles differed significantly from those of the ACS and CCS groups. The mean age of the control group was 56.2 years, and 46% of individuals in this group were female. The prevalence of coronary risk factors was low: 22.1% had hypertension, 7.8% had diabetes, and 19.2% had dyslipidemia, while 62.1% had no history of smoking.
Table 1.
Baseline Characteristics
| ACS (n=724) |
CCS (n=579) |
Control (n=2,407) |
P value | |
|---|---|---|---|---|
| Age (years) | 70.4±12.3 | 72.1±10.0 | 56.2±11.6*,† | <0.001 |
| Male | 551 (76.1) | 450 (77.7) | 1,321 (54.8)*,† | <0.0001 |
| Body mass index (kg/m2) | 24.0±3.8 | 24.3±3.9 | 23.1±5.1*,† | <0.001 |
| STEMI | 352 (48.6) | – | – | |
| Hypertension | 497 (68.6) | 442 (76.3)* | 534 (22.1)*,† | <0.0001 |
| Diabetes | 271 (37.4) | 245 (42.3) | 188 (7.8)*,† | <0.0001 |
| Dyslipidemia | 456 (62.9) | 399 (68.9)* | 463 (19.2)*,† | <0.0001 |
| Cerebral infarction | 45 (6.2) | 28 (4.8) | – | 0.330 |
| Prior myocardial infarction | 58 (8.0) | 87 (15.0) | – | 0.0001 |
| History of CABG | 16 (2.2) | 34 (5.8) | – | 0.0007 |
| Prior PCI | 113 (15.6) | 163 (28.1) | – | <0.0001 |
| Statin | 175 (24.1) | 386 (66.6)* | 302 (14.3)*,† | <0.0001 |
| PCSK9i | 0 (0) | 1 (0.1) | 0 (0) | 0.156 |
| Current smoker | 202 (27.9) | 77 (13.2)* | 264 (10.9)* | <0.0001 |
| Past smoker | 258 (35.6) | 289 (49.9)* | 648 (26.9)*,† | <0.0001 |
| Never smoker | 264 (36.4) | 213 (36.7) | 1,495 (62.1)*,† | <0.0001 |
| Hemoglobin (g/dL) | 13.2±2.2 | 13.3±5.4 | – | 0.198 |
| Hemoglobin A1c (%) | 6.1±1.1 | 6.2±1.1* | 5.4±0.5*,† | <0.001 |
| Albumin (g/dL) | 3.7±0.5 | 3.9±0.4* | 4.3±0.8*,† | <0.001 |
| C-reactive protein (mg/dL) | 0.15 [0.15–0.48] | 0.11 [0.11–0.41]* | 0.04 [0.02–0.09]*,† | <0.0001 |
| BUN (mg/dL) | 17.4 [13.7–22.2] | 17.4 [13.8–22.2] | 13.4 [11.2–15.8]*,† | <0.001 |
| Creatinine (mg/dL) | 0.86 [0.7–1.2] | 0.91 [0.75–1.13]* | 0.79 [0.68–0.92]*,† | <0.001 |
| eGFR (mL/min/1.73 m2) | 64.0 [48–79.2] | 59.9 [47–70.8]* | 69.6 [61.9–78.5]*,† | <0.001 |
| Uric acid (mg/dL) | 5.6±1.6 | 5.3±1.4* | 5.3±1.3* | <0.001 |
| Total cholesterol (mg/dL) | 184±45.6 | 155±36.0* | 205±33.9*,† | <0.001 |
| Triglyceride (mg/dL) | 87.5 [54–150] | 111 [80–161]* | 82 [60–115]*,† | <0.001 |
| LDL cholesterol (mg/dL) | 115±38 | 83±29* | 121±29*,† | <0.001 |
| HDL cholesterol (mg/dL) | 45±12 | 48±12* | 62±15*,† | <0.001 |
| BNP (pg/mL) | 349 [36–349] | 63 [24–191]* | – | <0.001 |
*P<0.05 vs. ACS; †P<0.05 vs. CCS. Data are presented as mean±standard deviation, median [IQR], or n (%). ACS, acute coronary syndrome; BNP, B-type natriuretic peptide; BUN, blood urea nitrogen; CABG, coronary artery bypass grafting; CCS, chronic coronary syndrome; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein; PCI, percutaneous coronary intervention; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; STEMI, ST-elevation myocardial infarction.
In contrast, the ACS and CCS groups differed in several characteristics, although age and sex distributions were comparable. The CCS group showed slightly higher rates of dyslipidemia and hypertension, as well as greater statin use and lower LDL-C levels, reflecting prior management of coronary risk factors. The proportion of current smokers was higher among patients with ACS.
Table 2 and Figure 2 illustrate lipoprotein(a) levels across the 3 groups. The control group had lower lipoprotein(a) levels and fewer individuals with elevated levels (≥30 or ≥50 mg/dL) compared with the ACS and CCS groups. Median lipoprotein(a) levels were similar in the ACS and CCS groups; however, the proportion of patients with high levels tended to be greater in the CCS group. Table 3 compares the percentages of individuals with elevated lipoprotein(a) levels (≥30 or ≥50 mg/dL) across the groups. The control group had lower proportions not only compared with the ACS and CCS groups but also relative to the combined CAD cohort.
Table 2.
Lipoprotein(a) Levels Across the 3 Groups
| ACS (n=724) |
CCS (n=579) |
Control (n=2,407) |
P value | |
|---|---|---|---|---|
| Lipoprotein(a) (mg/dL), median [IQR] | 13 [6–26] | 14 [7–30] | 10 [5–20]*,† | <0.001 |
| Lipoprotein(a) >30 mg/dL (%) | 19.1 | 26* | 13.1† | <0.001 |
| Lipoprotein(a) >50 mg/dL (%) | 7.8 | 11.5* | 4.7*,† | <0.001 |
*P<0.05 vs. ACS; †P<0.05 vs. CCS. Abbreviations as in Table 1.
Figure 2.
Distribution of serum levels of lipoprotein(a). (A) Lipoprotein(a) levels across the 3 groups. (B–D) Lipoprotein(a) levels in each group: acute coronary syndrome (ACS; B); chronic coronary syndrome (CCS; C); and control (D). The control group had lower lipoprotein(a) levels and fewer individuals with elevated levels (≥30, ≥50, or ≥70 mg/dL) than the ACS and CCS groups. Median lipoprotein(a) levels were similar between the ACS and CCS groups; however, the proportion of patients with high levels tended to be greater in the CCS group. IQR, interquartile range; SD, standard deviation.
Table 3.
Comparison of the Proportions of Individuals With Elevated Lipoprotein(a) Levels
| Odds ratio (95% CI) | P value | ||
|---|---|---|---|
| Individuals with lipoprotein(a) >30/total number of individuals with elevated lipoprotein(a) levels | |||
| CAD (ACS+CCS): 290/1,303 | Control: 317/2,407 | 1.88 (1.58–2.25) | <0.001 |
| ACS: 139/724 | Control: 317/2,407 | 1.56 (1.25–1.95) | <0.001 |
| CCS: 151/579 | Control: 317/2,407 | 2.32 (1.86–2.89) | <0.001 |
| ACS: 139/724 | CCS: 151/579 | 0.67 (0.51–0.87) | 0.003 |
| Individuals with lipoprotein(a) >50/total number of individuals with elevated lipoprotein(a) | |||
| CAD (ACS+CCS): 124/1,303 | Control: 114/2,407 | 1.88 (1.58–2.25) | <0.001 |
| ACS: 57/724 | Control: 114/2,407 | 1.56 (1.25–1.95) | 0.001 |
| CCS: 67/579 | Control: 114/2,407 | 2.32 (1.86–2.89) | <0.001 |
| ACS: 57/724 | CCS: 65/579 | 0.67 (0.51–0.87) | 0.002 |
CAD, coronary artery disease; CI, confidence interval. Other abbreviations as in Table 1.
When lipoprotein(a) levels were modeled on a logarithmic scale using restricted cubic splines, a dose-dependent association with ACS was observed (Figure 3A). A similar trend was evident for CCS, with a sharp increase in risk above approximately 20 mg/dL (Figure 3B).
Figure 3.
Restricted cubic spline curve of adjusted odds ratio for acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) according to lipoprotein(a) level. When the lipoprotein(a) level was modeled on a logarithmic scale using restricted cubic splines, a dose-dependent association with ACS was observed (A). A similar trend was evident for CCS, with a sharp increase in risk above approximately 20 mg/dL (B). The reference value was the median lipoprotein(a) level in the 1st quartile. Lp(a), lipoprotein(a).
Subgroup analyses of lipoprotein(a) levels are summarized in Table 4. Overall, no significant difference was observed between the ACS and CCS groups across subgroups, whereas lipoprotein(a) levels were consistently lower in the control group. When stratified by prior statin therapy, lipoprotein(a) levels did not differ significantly among the 3 groups in patients receiving statins. Among those without prior statin therapy, lipoprotein(a) levels remained lower in the control group (Table 5). No significant differences were observed between the ACS and CCS groups regardless of statin use.
Table 4.
Subgroup Analyses of Lipoprotein(a) Levels
| ACS | CCS | Control | P value | |
|---|---|---|---|---|
| Sex | ||||
| Male (n) | 551 | 450 | 1,321 | |
| Lipoprotein(a) (mg/dL) | 12 [6–25] | 13 [6–28] | 9 [5–17]*,† | <0.001 |
| Female (n) | 173 | 129 | 1,086 | |
| Lipoprotein(a) (mg/dL) | 15 [7.5–32.5] | 16 [7–35] | 11.5 [5–22]*,† | <0.001 |
| Age | ||||
| <70 years (n) | 301 | 208 | 2,035 | |
| Lipoprotein(a) (mg/dL) | 10 [5–24] | 11 [5–24] | 10 [5–19] | 0.145 |
| >70 years (n) | 422 | 371 | 372 | |
| Lipoprotein(a) (mg/dL) | 15 [7–28] | 15 [8–31] | 11.5 [6–22]*,† | <0.001 |
| Diabetes | ||||
| Yes (n) | 271 | 245 | 188 | |
| Lipoprotein(a) (mg/dL) | 12 [6–26] | 15 [7–30] | 9 [4–17]*,† | <0.001 |
| No (n) | 453 | 334 | 2,219 | |
| Lipoprotein(a) (mg/dL) | 14 [6–26.5] | 13.5 [6.75–30] | 10 [5–20]*,† | <0.001 |
| Chronic kidney disease | ||||
| >eGFR 60 (CKD−) (n) | 402 | 283 | 1,932 | |
| Lipoprotein(a) (mg/dL) | 12 [6–24] | 12 [5–24] | 10 [5–19]*,† | <0.001 |
| <eGFR 60 (CKD+) (n) | 322 | 296 | 475 | |
| Lipoprotein(a) (mg/dL) | 14 [6–29] | 16 [8–34.7] | 11 [5–23]*,† | <0.001 |
| Prior statin therapy | ||||
| Yes (n) | 175 | 386 | 302 | |
| Lipoprotein(a) (mg/dL) | 16 [6–30] | 14 [7–32] | 12.5 [7–26] | 0.362 |
| No (n) | 491 | 131 | 2,099 | |
| Lipoprotein(a) (mg/dL) | 13 [6–25] | 14 [7–27] | 9 [5–19]*,† | <0.001 |
| Baseline LDL cholesterol | ||||
| >120 (n) | 313 | 65 | 1,208 | |
| Lipoprotein(a) (mg/dL) | 15 [7–26] | 13 [6–27.5] | 12 [6–23]* | <0.001 |
| <120 (n) | 407 | 480 | 1,199 | |
| Lipoprotein(a) (mg/dL) | 12 [6–26] | 15 [7–30] | 8 [4–17]*,† | <0.001 |
*P<0.05 vs. ACS; †P<0.05 vs. CCS. Data are presented as median [IQR]. Abbreviations as in Table 1.
Table 5.
Comparison of the Lipoprotein(a) Levels in Patients With or Without Prior Statin Therapy
| Lipoprotein(a) (mg/dL) |
Lipoprotein(a) (mg/dL) |
P value | ||
|---|---|---|---|---|
| Patients with prior statin therapy | ||||
| CAD (ACS+CCS; n=562) | 15 [7–32] | Control (n=302) | 12.5 [7–26] | 0.161 |
| ACS (n=175) | 16 [5–30] | Control (n=302) | 12.5 [7–26] | 0.224 |
| CCS (n=386) | 14 [7–32] | Control (n=302) | 12.5 [7–26] | 0.226 |
| ACS (n=175) | 16 [5–30] | CCS (n=386) | 14 [7–32] | 0.416 |
| Patients without prior statin therapy | ||||
| CAD (ACS+CCS; n=622) | 13 [6–25] | Control (n=2,099) | 9 [5–19] | <0.001 |
| ACS (n=491) | 13 [6–25] | Control (n=2,099) | 9 [5–19] | <0.001 |
| CCS (n=131) | 14 [7–27] | Control (n=2,099) | 9 [5–19] | <0.001 |
| ACS (n=491) | 13 [6–25] | CCS (n=131) | 14 [7–27] | 0.508 |
Data are presented as median [IQR]. Abbreviations as in Tables 1,3.
Discussion
This study evaluated the distribution of lipoprotein(a) levels among patients with CAD – including ACS and CCS – who underwent PCI and among healthy individuals from the same region and period. Elevated lipoprotein(a) levels are considered an independent risk factor for ASCVD;6,7 however, no studies have previously compared lipoprotein(a) levels between patients with CAD and healthy individuals in the same time period and region. The median serum lipoprotein(a) levels were 13 mg/dL in the ACS group, 14 mg/dL in the CCS group, and 10 mg/dL in the control group, consistent with previous findings in Japanese populations.24 Because patients with CAD tend to have higher lipoprotein(a) levels than healthy individuals, interventions including strict lipid management are necessary. In Japan, target thresholds of <30 and <50 mg/dL have been proposed as appropriate for risk assessment.25 Prior studies in patients with ACS undergoing PCI reported a median lipoprotein(a) level of 16.0 mg/dL, with 26.3% and 10.5% of participants exceeding levels of 30 and 50 mg/dL, respectively.25 Our findings align with these results, with even lower levels in the control group. Approximately 10% of the general Asian population has lipoprotein(a) levels ≥50 mg/dL, compared with 15–30% globally,26 and substantially higher levels have been reported among individuals of African descent.27
Recent studies have emphasized the association between elevated lipoprotein(a) levels and ASCVD, reinforcing its clinical utility as a biomarker.28–30 Nonetheless, lipoprotein(a) testing remains underutilized.19,31 At KPCH, routine lipoprotein(a) measurement has been implemented for nearly all patients undergoing PCI since 2019, enabling comparison with a large cohort of healthy individuals. In this study, lipoprotein(a) levels were lower in the control group than in the ACS and CCS groups, consistent with the findings of prior research showing lower levels in primary prevention than in secondary prevention populations.24 Although previous studies associated higher lipoprotein(a) levels with ACS,32,33 our results showed slightly higher levels in the CCS group. This may reflect the observation that many patients with CCS underwent elective or staged PCI and were receiving statins at the time of evaluation. Indeed, LDL-C levels were lower in the CCS group than in the ACS group. When analyses were limited to patients who were not on statins, LDL-C levels did not differ significantly between ACS and CCS.
Lipoprotein(a) levels vary according to individual characteristics.27 Higher levels have been reported among females and older adults, consistent with our findings. Lipoprotein(a) also tends to increase with impaired renal function and to decrease in individuals with diabetes.34,35 However, studies examining sex-based differences in Japanese populations have produced inconsistent results,24,36 underscoring the need for larger epidemiological investigations. Elevated lipoprotein(a) levels have also been observed among younger patients with ACS,37 suggesting that screening should not be limited by age or demographic factors.
Current guidelines strongly emphasize aggressive LDL-C reduction for ASCVD prevention.28,38,39 Recent Japanese real-world evidence suggests that protocol- or pathway-based intensive lipid-lowering strategies after ACS or acute myocardial infarction can improve LDL-C target attainment and may reduce subsequent cardiovascular events.40–42 Although lipoprotein(a) correlates with LDL-C, it is recognized as an independent risk factor for cardiovascular events.43,44 Evidence indicates that lowering LDL-C alone may not sufficiently mitigate lipoprotein(a)-related risk.45 Statins do not reduce lipoprotein(a) levels, whereas PCSK9 inhibitors46,47 and nicotinic acid derivatives48 can achieve reductions. PCSK9 inhibitors have yielded additional ASCVD risk reduction in patients with well-controlled LDL-C but elevated lipoprotein(a).14 Although therapeutic options specifically targeting lipoprotein(a) are currently limited in Japan, identifying and monitoring high-risk individuals remain crucial for optimal management.
Study Limitations
This study has several limitations. First, it was a single-center, retrospective, observational study conducted in a regional Japanese population, limiting generalizability to other ethnic or geographic groups. Second, the sample size was modest. Third, the CAD group was restricted to patients undergoing PCI. KPCH does not maintain a database of patients with CAD who did not undergo PCI; thus, those receiving drug therapy or coronary artery bypass grafting (CABG) were not included. Excluding patients who received CABG may have led to the underestimation of observed lipoprotein(a) levels as a result of omitting individuals with more advanced atherosclerosis, while excluding patients who did not undergo PCI may have led to an overestimation of observed lipoprotein(a) levels. This may affect the generalizability of the findings to all patients with CAD. Fourth, individuals in the control group were those undergoing health check-ups at KPCH and may not represent the general healthy population. Nevertheless, the inclusion of nearly all patients undergoing coronary intervention for ACS or CCS during the study period provides a realistic representation of current regional trends. Last, existing immunoassays for lipoprotein(a) measurement vary in calibration, which may influence quantitative comparisons.49 Despite these limitations, this study offers valuable insights into lipoprotein(a) distribution in an East Asian cohort.
Conclusions
This study characterized lipoprotein(a) distribution among patients with CAD (ACS and CCS) and healthy individuals. Lipoprotein(a) levels were higher in patients with CAD than in the control group, supporting its role as an independent cardiovascular risk marker. Large-scale studies and the development of targeted lipoprotein(a)-lowering therapies are warranted to improve risk assessment and management in this population.
Disclosures
The authors declare that there are no conflicts of interest.
IRB Information
This study was approved by the Kagawa prefectural central hospital Ethics Committee (Approval no. 1091).
Acknowledgments
We thank Ms. Ishikawa for her excellent technical support. We also thank Editage for English language editing and their assistance in creating the graphical abstract for this paper.
Funding Statement
Sources of Funding: No funding to declare.
Data Availability
The deidentified participant data will not be shared.
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Data Availability Statement
The deidentified participant data will not be shared.