Association of Lipoprotein (a) and Standard Modifiable Cardiovascular Risk Factors With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry.

BACKGROUND: Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). METHODS AND RESULTS: This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as <50th percentile. The primary outcome was fatal or nonfatal AMI. A combination of natural language processing algorithms, International Classification of Diseases (ICD) codes, and laboratory data was used to identify the outcome and covariates. A total of 6238 patients met the eligibility criteria. The median age was 54 (interquartile range, 43-65) years, and 45% were women. Overall, 23.7% had no SMuRFs, and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (interquartile range, 4.2-12.8) years, the incidence of AMI increased gradually, with higher number of SMuRFs among patients with high (log-rank P=0.031) and low Lp(a) (log-rank P<0.001). Across all SMuRF subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) versus low Lp(a). The risk of high Lp(a) was similar to having 2 SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained significantly associated with the primary outcome (hazard ratio, 2.9 [95% CI, 2.0-4.3]; P<0.001). CONCLUSIONS: Among patients with no prior atherosclerotic cardiovascular disease, high Lp(a) is associated with significantly higher risk for first AMI regardless of the number of SMuRFs.

The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study.

BACKGROUND: Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. METHODS: This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. RESULTS: Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45-0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34-0.75; P < 0.001), without a significant increase of adverse reactions. CONCLUSION: Current levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.

Association of Lipoprotein(a) Levels With Myocardial Infarction in Patients With Low-Attenuation Plaque.

BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.

Resilient Older Subjects with Heterozygous Familial Hypercholesterolemia, Baseline Differences and Associated Factors.

Despite elevated low-density lipoprotein (LDL) cholesterol levels, some older subjects with heterozygous familial hypercholesterolemia (HeFH) do not develop atherosclerotic cardiovascular disease (ACVD) during their lifetime. The factors related to this resilient state have not been fully established. The aim of this study was to evaluate differential characteristics between older HeFH subjects with and without ACVD and factors associated with the presence of ACVD. Subjects were part of the Spanish Atherosclerosis Society Dyslipidemia Registry, and those ≥ 70 years old and with HeFH were included. Baseline characteristics of these subjects with and without ACVD were compared. A multivariate analysis was performed to assess factors associated with the presence of ACVD. A total of 2148 subjects with HeFH were included. Resilient subjects were mostly female, younger and presented fewer comorbidities with respect to the ACVD group. Subjects without ACVD had higher baseline high-density lipoprotein (HDL) cholesterol (55.8 ± 17.1 vs. 47.9 ± 15.4 mg/dL; p < 0.001) and lower lipoprotein(a) [Lp(a)] (53.4 ± 67.9 vs. 66.6 ± 85.6 mg/dL; p < 0.001) levels with respect to those in the ACVD group. Lp(a) and the presence of ≥3 risk factors were associated with the presence of ACVD.

Predicting Pulmonary Embolism in Total Joint Arthroplasty Patients A Pilot Study.

Postoperative venous thromboembolism (VTE) is a common and costly complication following total joint arthroplasty (TJA). Development of a refined thrombophilic screening panel will better equip clinicians to identify patients at high-est risk for developing VTEs. In this pilot study, 62 high-risk TJA recipients who had developed pulmonary emboli (PE) within 90-days of surgery were eligible to participate. Of these patients, 14 were enrolled and subsequently adminis-tered a pre-determined panel of 18 hematologic tests with the aim of identifying markers that are consistently elevated or deficient in patients developing PE. A separate cohort of seven high-risk TJA recipients who did not report a symp-tomatic VTE within 90-days of surgery were then enrolled and Factor VIII and lipoprotein(a) levels were assessed. The most common aberrance was noted in 10 patients (71.4%) who had elevated levels of Factor VIII followed by five patients (35.7%) who had elevated levels of lipoprotein(a). Factor VIII was significantly prevalent (p < 0.001) while lipoprotein(a) failed to achieve statistical significance (p = 0.0708). Of the patients who were within normal limits of Factor VIII, three-fourths were "high-normal" with Fac-tor VIII levels within 5% of the upper limit of normal. This study demonstrates the potential utility of this hematologic panel as part of a perioperative screening protocol aimed at identifying patients at risk for developing VTEs. However, future larger scale studies assessing the capabilities and limitations of our findings are warranted.

Association between lipoprotein(a) plasma levels and diabetic nephropathy in Han Chinese patients with type 2 diabetes mellitus.

The goal of this study was to evaluate the relationship between serum lipoprotein(a) [Lp(a)] levels and diabetic nephropathy (DN) among Han Chinese individuals with type 2 diabetes mellitus (T2DM). This retrospective analysis comprised a consecutive case series of 767 grown-up patients with T2DM (199 among them with DN) hospitalized in the Department of Endocrinology at the The First Affiliated Hospital of Anhui Medical University from February 20220 to February 2021. Clinical data and other laboratory measurements, such as glycated hemoglobin (HbA1c), were extracted from medical records and compared among groups. Clinical characteristics according to Lp(a) quartiles were also studied. Univariate and multivariate regression analysis were used to examine the relationship between serum Lp(a) and DN. Patients with DN had a longer disease duration, higher HbA1c, higher level of Lp(a), and were more likely to have diabetic retinopathy (DR) than those without DN (P < 0.005 for each). With regard to the Lp(a) quartile group, patients with a higher Lp(a) concentration were more likely to have DN and have higher level of HbA1c during the study (P for trend < 0.005 for each). After adjusting for several confounding factors, the development of DN was significantly associated with the serum Lp(a) level (P = 0.026, comparing the 4th vs 1st quartile of Lp(a)) according to multivariate regression analysis. The receiver operating characteristic (ROC) curves for DN development using serum Lp(a) showed that the area under the receiver operating characteristic curves (AUC) was 0.590 (P < 0.001). Findings from this study demonstrated that the DN was independently associated with the serum Lp(a) level in patients with T2DM in this retrospective study.

Confounding Factors Responsible for Elevated Lp(a) Levels in Patients with Coronary Artery Disease.

BACKGROUND: Cardiovascular diseases (CVDs) are a leading cause of global mortality, motivating research into novel approaches for their management. Lipoprotein(a) (Lp(a)), a unique lipoprotein particle, has been implicated in atherosclerosis and thrombosis, suggesting its potential as a therapeutic target for CVDs. AIM: This study aimed to investigate the association of Lp(a) levels with various cardiovascular parameters and events among patients with confirmed cardiovascular disease. METHODOLOGY: A prospective study was conducted, enrolling 600 participants, predominantly comprising males (79%), with a mean age of 52.78 ± 0.412 years diagnosed with cardiovascular disease. The follow-up was done for 18 months. Patient demographics, blood investigations, and occurrence of major adverse cardiac events (MACE) were collected. SPSS version 21 was used to statistically analyze the relationships between elevated Lp(a) levels and factors such as age, glycated hemoglobin, mortality, MACE, cardiac death, target vessel revascularization, and stroke. RESULTS: The study revealed significant (P < 0.05) associations between elevated Lp(a) levels and advanced age, increased glycated hemoglobin levels, as well as occurrences of all-cause mortality, MACE, cardiac death, target vessel revascularization, and stroke. Notably, a significant (P < 0.05), association between high Lp(a) levels and acute coronary syndrome (ACS) emerged, suggesting Lp(a)'s role in advanced cardiac events. CONCLUSION: The findings highlight the potential significance of Lp(a) as a notable risk factor in cardiovascular health. The observed associations between elevated Lp(a) and adverse cardiovascular events, including ACS, underscore its pathogenic role. Consequently, this study supports the rationale for further research into Lp(a)-specific therapeutic interventions, offering substantial promise in refining the management strategies for cardiovascular diseases.

Discovery of potent small-molecule inhibitors of lipoprotein(a) formation.

Lipoprotein(a) (Lp(a)), an independent, causal cardiovascular risk factor, is a lipoprotein particle that is formed by the interaction of a low-density lipoprotein (LDL) particle and apolipoprotein(a) (apo(a))1,2. Apo(a) first binds to lysine residues of apolipoprotein B-100 (apoB-100) on LDL through the Kringle IV (KIV) 7 and 8 domains, before a disulfide bond forms between apo(a) and apoB-100 to create Lp(a) (refs. 3-7). Here we show that the first step of Lp(a) formation can be inhibited through small-molecule interactions with apo(a) KIV7-8. We identify compounds that bind to apo(a) KIV7-8, and, through chemical optimization and further application of multivalency, we create compounds with subnanomolar potency that inhibit the formation of Lp(a). Oral doses of prototype compounds and a potent, multivalent disruptor, LY3473329 (muvalaplin), reduced the levels of Lp(a) in transgenic mice and in cynomolgus monkeys. Although multivalent molecules bind to the Kringle domains of rat plasminogen and reduce plasmin activity, species-selective differences in plasminogen sequences suggest that inhibitor molecules will reduce the levels of Lp(a), but not those of plasminogen, in humans. These data support the clinical development of LY3473329-which is already in phase 2 studies-as a potent and specific orally administered agent for reducing the levels of Lp(a).

Lipoprotein(a) as a blood marker for large artery atherosclerosis stroke etiology: validation in a prospective cohort from a swiss stroke center.

BACKGROUND: Lipoprotein (a) [Lp(a)] serum levels are highly genetically determined and promote atherogenesis. High Lp(a) levels are associated with increased cardiovascular morbidity. Serum Lp(a) levels have recently been associated with large artery atherosclerosis (LAA) stroke. We aimed to externally validate this association in an independent cohort. METHODS: This study stems from the prospective multicentre CoRisk study (CoPeptin for Risk Stratification in Acute Stroke patients [NCT00878813]), conducted at the University Hospital Bern, Switzerland, between 2009 and 2011, in which Lp(a) plasma levels were measured within the first 24 hours after stroke onset. We assessed the association of Lp(a) with LAA stroke using multivariable logistic regression and performed interaction analyses to identify potential effect modifiers. RESULTS: Of 743 patients with ischaemic stroke, 105 (14%) had LAA stroke aetiology. Lp(a) levels were higher for LAA stroke than non-LAA stroke patients (23.0 nmol/l vs 16.3 nmol/l, p = 0.01). Multivariable regression revealed an independent association of log10and#xA0;Lp(a) with LAA stroke aetiology (aOR 1.47 [95% CI 1.03and#x2013;2.09], p = 0.03). The interaction analyses showed that Lp(a) was not associated with LAA stroke aetiology among patients with diabetes. CONCLUSIONS: In a well-characterised cohort of patients with ischaemic stroke, we validated the association of higher Lp(a) levels with LAA stroke aetiology, independent of traditional cardiovascular risk factors. These findings may inform randomised clinical trials investigating the effect of Lp(a) lowering agents on cardiovascular outcomes. The CoRisk (CoPeptin for Risk Stratification in Acute Patients) study is registered on ClinicalTrials.gov. REGISTRATION NUMBER: NCT00878813.

Independent Relationship of Lipoprotein(a) and Carotid Atherosclerosis With Long-Term Risk of Cardiovascular Disease.

BACKGROUND: Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. METHODS AND RESULTS: A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person-years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long-term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19-2.21) than those with Lp(a) <10 mg/dL, and they exhibited a 10-year ASCVD incidence of 11.7%. This association exists even after adjusting for prevalent plaque. Moreover, participants with Lp(a) ≥30 mg/dL and prevalent plaque had a significant 4.18 times higher ASCVD risk than those with Lp(a) <30 mg/dL and no plaque. CONCLUSIONS: Higher Lp(a) concentrations are independently associated with long-term ASCVD risk and may exaggerate cardiovascular risk when concomitant with atherosclerotic plaque.

Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a): A Randomized Clinical Trial.

Importance: Lipoprotein(a) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic stenosis, with no pharmacological treatments approved by regulatory authorities. Objectives: To assess the safety and tolerability of zerlasiran, a short interfering RNA targeting hepatic synthesis of apolipoprotein(a), and effects on serum concentrations of lipoprotein(a). Design, Setting, and Participants: Single- and multiple-dose study in healthy participants and patients with stable ASCVD, respectively, with lipoprotein(a) serum concentrations greater than 150 nmol/L, conducted at 7 research sites in the US, the Netherlands, UK, and Australia between November 18, 2020, and February 8, 2023, with last follow-up on August 23, 2023. Interventions: Participants were randomized to receive (1) a single subcutaneous dose of placebo (n = 8), zerlasiran 300 mg (n = 6) or 600 mg (n = 6); or (2) 2 doses of placebo (n = 9), zerlasiran 200 mg (n = 9) at a 4-week interval or 300 mg (n = 9) or 450 mg (n = 9) at an 8-week interval. Main Outcomes Measures: The primary outcome was safety and tolerability. Secondary outcomes included serum levels of zerlasiran and effects on lipoprotein(a) serum concentrations. Results: Among 37 patients in the multiple-dose group (mean age, 56 [SD, 10.4] years; 15 [42%] women), 36 completed the trial. Among 14 participants with extended follow-up after single doses, 13 completed the trial. There were no serious adverse events. Median baseline lipoprotein(a) concentrations in the multiple-dose group were 288 (IQR, 199-352) nmol/L. Median changes in lipoprotein(a) concentration at 365 days after single doses were 14% (IQR, 13% to 15%) for the placebo group, -30% (IQR, -51% to -18%) for the 300 mg of zerlasiran group, and -29% (IQR, -39% to -7%) for the 600-mg dose group. After 2 doses, maximal median changes in lipoprotein(a) concentration were 19 (IQR, -17 to 28) nmol/L for the placebo group, -258 (IQR, -289 to -188) nmol/L for the 200 mg of zerlasiran group, -310 (IQR, -368 to -274) nmol/L for the 300-mg dose group, and -242 (IQR, -343 to -182) nmol/L for the 450-mg dose group, with maximal median percent change of 7% (IQR, -4% to 21%), -97% (IQR, -98% to -95%), -98% (IQR, -99% to -97%), and -99% (IQR, -99% to -98%), respectively, attenuating to 0.3% (IQR, -2% to 21%), -60% (IQR, -71% to -40%), -90% (IQR, -91% to -74%), and -89% (IQR, -91% to -76%) 201 days after administration. Conclusions: Zerlasiran was well tolerated and reduced lipoprotein(a) concentrations with infrequent administration. Trial Registration: ClinicalTrials.gov Identifier: NCT04606602.

Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolaemia: An expert consensus statement from ERKNet and ESPN.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

Causal association of blood lipids with all-cause and cause-specific mortality risk: a Mendelian randomization study.

Dyslipidemia has long been implicated in elevating mortality risk; yet, the precise associations between lipid traits and mortality remained undisclosed. Our study aimed to explore the causal effects of lipid traits on both all-cause and cause-specific mortality. One-sample Mendelian randomization (MR) with linear and nonlinear assumptions was conducted in a cohort of 407,951 European participants from the UK Biobank. Six lipid traits, consisting of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a), were included to investigate the causal associations with mortality. Two-sample MR was performed to replicate the association between each lipid trait and all-cause mortality. Univariable MR results showed that genetically predicted higher ApoA1 was significantly associated with a decreased all-cause mortality risk (HR[95% CI]:0.93 [0.89-0.97], P value = 0.001), which was validated by the two-sample MR analysis. Higher lipoprotein(a) was associated with an increased risk of all-cause mortality (1.03 [1.01-1.04], P value = 0.002). Multivariable MR confirmed the direct causal effects of ApoA1 and lipoprotein(a) on all-cause mortality. Meanwhile, nonlinear MR found no evidence for nonlinearity between lipids and all-cause mortality. Our examination into cause-specific mortality revealed a suggestive inverse association between ApoA1 and cancer mortality, a significant positive association between lipoprotein(a) and cardiovascular disease mortality, and a suggestive positive association between lipoprotein(a) and digestive disease mortality. High LDL-C was associated with an increased risk of cardiovascular disease mortality but a decreased risk of neurodegenerative disease mortality. The findings suggest that implementing interventions to raise ApoA1 and decrease lipoprotein(a) levels may improve overall health outcomes and mitigate cancer and digestive disease mortality.

Plasma Biomarker Profiles for Premature and Nonpremature Coronary Heart Disease in Women.

BACKGROUND: Premature coronary heart disease (CHD) is a major cause of death in women. We aimed to characterize biomarker profiles of women who developed CHD before and after age 65 years. METHODS: In the Women's Health Study (median follow-up 21.5 years), women were grouped by age and timing of incident CHD: baseline age <65 years with premature CHD by age 65 years (25 042 women; 447 events) and baseline age ≥65 years with nonpremature CHD (2982 women; 351 events). Associations of 44 baseline plasma biomarkers measured using standard assays and a nuclear magnetic resonance (NMR)-metabolomics assay were analyzed using Cox models adjusted for clinical risk factors. RESULTS: Twelve biomarkers showed associations only with premature CHD and included lipoprotein(a), which was associated with premature CHD [adjusted hazard ratio (HR) per SD: 1.29 (95% CI 1.17-1.42)] but not with nonpremature CHD [1.09(0.98-1.22)](Pinteraction = 0.02). NMR-measured lipoprotein insulin resistance was associated with the highest risk of premature CHD [1.92 (1.52-2.42)] but was not associated with nonpremature CHD (Pinteraction <0.001). Eleven biomarkers showed stronger associations with premature vs nonpremature CHD, including apolipoprotein B. Nine NMR biomarkers showed no association with premature or nonpremature CHD, whereas 12 biomarkers showed similar significant associations with premature and nonpremature CHD, respectively, including low-density lipoprotein (LDL) cholesterol [1.30(1.20-1.45) and 1.22(1.10-1.35)] and C-reactive protein [1.34(1.19-1.50) and 1.25(1.08-1.44)]. CONCLUSIONS: In women, a profile of 12 biomarkers was selectively associated with premature CHD, driven by lipoprotein(a) and insulin-resistant atherogenic dyslipoproteinemia. This has implications for the development of biomarker panels to screen for premature CHD.