Exploring Coronary Artery Disease Outcome using Lipoprotein (a) vs ASCVD 10-Year Risk Score

Introduction/Background

Lipoprotein A (Lp(a)) was discovered in 1963 as an apolipoprotein B (apoB)-containing lipoprotein. Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein (a). This novel marker of cardiovascular disease acts through induction of vascular inflammation, atherogenesis, calcification, and thrombosis¹. Evidence from mechanistic, observational, and genetic studies support a causal role of Lp(a) in the development of cardiovascular disease, including coronary heart disease and peripheral arterial disease, as well as aortic valve stenosis, and likely also ischemic stroke². Lp(a) is a quantitative genetic trait with a very broad and skewed distribution, which is largely controlled by genetic variants at the LPA locus on chromosome 6q27³. Lp(a) levels are estimated to be 90% hereditary. Elevated LP(a) levels have been found to be predictive of ASCVD risk over 10 years⁴. One of the main obstacles to the clinical use of Lp(a) is that its measurement and target levels have not been standardized. Several available assays report results in mass (mg/dL) instead of concentration (nmol/L), the latter of which is preferred⁵. This is because lipoprotein “particle number” (molar concentration) has been found to be superior to component-based metrics for cardiovascular disease risk prediction⁶.

Purpose

The purpose of this retrospective cohort study is to investigate the relationship between (Lp(a), 10-year ASCVD risk score, and the incidence of coronary artery disease. By analyzing data from a large cohort of patients, this preliminary study aims to determine predictiveness of Lp(a) levels vs 10-year ASCVD risk score for coronary artery disease and to assess their potential utility in identifying individuals at increased risk for this condition.

Lp(a) Standardization

HEART UK Lp(a) Grade⁷ was utilized to identify patients with measured Lp(a) levels as follows:

• 32-90 nmol/L - minor
• 90-200 nmol/L - moderate
• 200-400 nmol/L - high
  
• > 400 nmol/L - very high

ASCVD 10-Year Risk Score

• <5% - Low risk
• 5-7.5% - Borderline risk
• 7.5-<20% - Intermediate risk
• >20% - High risk

Study Population

Inclusion criteria: 

1. Using ASCVD 10-Year Risk Score guideline: Age (Years) 40-75 
2. Lp(a) nmol/L (2018-2023) via Quest/Labcorp
3. Total Cholesterol (mg/dL), HDL (mg/dL)
4. Race, Gender, Smoking Hx, Diabetes, HTN, HTN Treatment
5. History of acute coronary event(s)

Statistical Methods

1. Pearson Chi-Square (Bi Lp(a) Levels * ASCVD outcome)
2. Binary Linear Regression Model (ASCVD Risk score * ASCVD outcome, Lp(a) *ASCVD outcome)

Patient Demographics

• Total Patients: 562
• Age Range: 40-75 (mean: 55.2, SD=9.9)
• Male: 49.1%
• Female: 50.9%
• White: 58.2%
• Black: 6.4%
• Other: 35.4% (Asian, Hispanic)

Risk Factors

• Non-Smokers: 66.2%
• Smokers: 33.8%
• HTN with treatment: 51.6%
• Diabetes: 26%

ASCVD outcome
Coronary Events: 12.8%

ASCVD Score and Risk Level

The mean ASCVD score for patients was 10.3 (SD=10.9) based on the ASCVD risk assessment. Based on the study categorization, the majority of patients fell into the low-risk category (45.6%), 8.9% were identified as having borderline risk, 29.4% as having an intermediate risk, and 16.2% were determined to be in the high-risk category. 

Lp(a)

The mean of reported Lp(a) for patients was 55.2 nmol/L (SD=82.1 nmol/L). Based on the HEART UK grading system, 56.9% (320) of the sample was categorized as negligible, 20.8% (117) as minor, 16.4% (92) as moderate, 5.2% (29) as high, and 0.7% (4) were assigned to the very high category.

Pearson Chi-Square

Chi-Square tests of association were run to assess for a possible association between categorical variables ASCVD Risk Level and ASCVD event, as well as Lp(a) Level and ASCVD event. There is a statistically significant association between Lp(a) Level and ASCVD event, X(1) = 7.44, p < .01. A statistically significant association between ASCVD Risk Level and ASCVD event was also found, X(3) = 56.6, p < .001.

Binary Linear Regression

The logistic regression model was statistically significant, X²(4) = 60.06 with a p < .001. The model explained that patients with a high ASCVD risk score had an 18.9% increased risk of cardiac events in 10 years. Furthermore, this model correctly calculated risk at 87.2% of cases overall. This places ASCVD Risk score assessment as a significant predictor of having an ASCVD event with a  p <.001. More extensively, those in the Intermediate Risk category being 4.7% more likely to have an ASCVD and those in the High-Risk category being 13.1% more likely to have an ASCVD.

Lp(a) Level is also significant, p <.01, with those having moderate, high, or very high Lp(a) levels being 2.2% more likely to have an ASCVD.