Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An expert clinical consensus from the national lipid association.

This National Lipid Association (NLA) Expert Clinical Consensus provides an overview of the physiologic and clinical considerations regarding the role of apolipoprotein B (apoB) measurement to guide clinical care based on the available scientific evidence and expert opinion. ApoB represents the total concentration of atherogenic lipoprotein particles in the circulation and more accurately reflects the atherogenic burden of lipoproteins when compared to low-density lipoprotein cholesterol (LDL-C). ApoB is a validated clinical measurement that augments the information found in a standard lipoprotein lipid panel; therefore, there is clinical value in using apoB in conjunction with a standard lipoprotein lipid profile when assessing risk and managing lipid-lowering therapy (LLT). ApoB has been shown to be superior to LDL-C in risk assessment both before and during treatment with LLT. In individuals, there can be discordance between levels of LDL-C and apoB, as well as LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C), despite high levels of population-wide correlation. When there is discordance between LDL-C and apoB, or LDL-C and non-HDL-C, atherosclerotic cardiovascular disease risk generally aligns better with apoB or non-HDL-C. Additionally, apoB can be used in tandem with standard lipoprotein lipid measurements to diagnose distinct lipoprotein phenotypes. ApoB testing can inform clinical prognosis and care, as well as enable family cascade screening, when an inherited lipoprotein syndrome is identified. The NLA and other organizations will continue to educate clinicians about the role of apoB measurement in improving clinical risk assessment and dyslipidemia management. An urgent need exists to improve access and reimbursement for apoB testing.

Triglyceride Levels, Alirocumab Treatment, and Cardiovascular Outcomes After an Acute Coronary Syndrome.

BACKGROUND: It is unknown whether clinical benefit of proprotein convertase subtilisin/kexin type 9 inhibitors is associated with baseline or on-treatment triglyceride concentrations. OBJECTIVES: This study sought to examine relations between triglyceride levels and the effect of alirocumab vs placebo on cardiovascular outcomes using prespecified and post hoc analyses of the ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial. METHODS: Patients with recent acute coronary syndrome (ACS) (n = 18,924) and elevated atherogenic lipoproteins despite optimized statin therapy were randomized to alirocumab 75 to 150 mg or matching placebo every 2 weeks subcutaneously. Major adverse cardiovascular events (MACE) were examined in relation to continuous or dichotomous triglyceride concentrations. RESULTS: Median baseline triglyceride concentration was 129 mg/dL. In both treatment groups, a 10-mg/dL higher baseline concentration was associated with an adjusted MACE HR of 1.008 (95% CI: 1.003-1.013; P < 0.005). Baseline triglycerides ≥150 vs <150 mg/dL were associated with a HR of 1.184 (95% CI: 1.080-1.297; P < 0.005). Versus placebo, alirocumab reduced low-density lipoprotein cholesterol from baseline (average, 54.7%) and reduced MACE (HR: 0.85; 95% CI: 0.78-0.93). At month 4, triglyceride levels were reduced from baseline by median 17.7 mg/dL (P < 0.001) and 0.9 mg/dL (P = NS) with alirocumab and placebo, respectively. A 10-mg/dL decline from baseline in triglycerides was associated with lower subsequent risk of MACE with placebo (HR: 0.988; 95% CI: 0.982-0.995; P < 0.005) but not with alirocumab (HR: 0.999; 95% CI: 0.987-1.010; P = 0.82). CONCLUSIONS: Among patients with recent ACS on optimized statin therapy, baseline triglycerides was associated with cardiovascular risk. However, the reduction in triglycerides with alirocumab did not contribute to its clinical benefit. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).

Alirocumab and cardiovascular outcomes according to sex and lipoprotein(a) after acute coronary syndrome: a report from the ODYSSEY OUTCOMES study.

BACKGROUND: The ODYSSEY OUTCOMES trial (NCT01663402) compared the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo on major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS). OBJECTIVE: We assessed efficacy and safety of alirocumab versus placebo according to sex and lipoprotein(a) level. METHODS: This prespecified analysis compared the effects of alirocumab versus placebo on lipoproteins, MACE (coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischemic stroke, unstable angina requiring hospitalization), death, total cardiovascular events, and adverse events in 4762 women and 14,162 men followed for a median of 2.8 years. In post-hoc analysis, we evaluated total cardiovascular events according to sex, baseline lipoprotein(a), and treatment. RESULTS: Women were older, had higher baseline low-density lipoprotein cholesterol (LDL-C) levels (89.6 vs 85.3 mg/dL) and lipoprotein(a) (28.0 vs 19.3 mg/dL) and had more co-morbidities than men. At 4 months, alirocumab lowered LDL-C by 49.4 mg/dL in women and 54.0 mg/dL in men and lipoprotein(a) by 9.7 and 8.1 mg/dL, respectively (both p < 0.0001). Alirocumab reduced MACE, death, and total cardiovascular events similarly in both sexes. In the placebo group, lipoprotein(a) was a risk factor for total cardiovascular events in women and men. In both sexes, reduction of total cardiovascular events was greater at higher baseline lipoprotein(a), but this effect was more evident in women than men (pinteraction=0.08). Medication adherence and adverse event rates were similar in both sexes. CONCLUSIONS: Alirocumab improves cardiovascular outcomes after ACS irrespective of sex. Reduction of total cardiovascular events was greater at higher baseline lipoprotein(a).

Low-Density Lipoprotein Cholesterol Testing Following Myocardial Infarction Hospitalization Among Medicare Beneficiaries.

Background: Low-density lipoprotein cholesterol (LDL-C) is used to guide lipid-lowering therapy after a myocardial infarction (MI). Lack of LDL-C testing represents a missed opportunity for optimizing therapy and reducing cardiovascular risk. Objectives: The purpose of this study was to estimate the proportion of Medicare beneficiaries who had their LDL-C measured within 90 days following MI hospital discharge. Methods: We conducted a retrospective cohort study of Medicare beneficiaries ≥66 years of age with an MI hospitalization between 2016 and 2020. The primary analysis used data from all beneficiaries with fee-for-service coverage and pharmacy benefits (532,767 MI hospitalizations). In secondary analyses, we used data from a 5% random sample of beneficiaries with fee-for-service coverage without pharmacy benefits (10,394 MI hospitalizations), and from beneficiaries with Medicare Advantage (176,268 MI hospitalizations). The proportion of beneficiaries who had their LDL-C measured following MI hospital discharge was estimated accounting for the competing risk of death. Results: In the primary analysis (mean age 76.9 years, 84.4% non-Hispanic White), 29.9% of beneficiaries had their LDL-C measured within 90 days following MI hospital discharge. Among Hispanic, Asian, non-Hispanic White, and non-Hispanic Black beneficiaries, the 90-day postdischarge LDL-C testing was 33.8%, 32.5%, 30.0%, and 26.0%, respectively. Postdischarge LDL-C testing within 90 days was highest in the Middle Atlantic (36.4%) and lowest in the West North Central (23.4%) U.S. regions. In secondary analyses, the 90-day postdischarge LDL-C testing was 26.9% among beneficiaries with fee-for-service coverage without pharmacy benefits, and 28.6% among beneficiaries with Medicare Advantage coverage. Conclusions: LDL-C testing following MI hospital discharge among Medicare beneficiaries was low.

Endogenous androgens, coronary atheroma and remodeling in women with suspected ischemic heart disease: A report from the Women's Ischemia Syndrome Evaluation (WISE) study.

Background: Women have smaller coronary size than men independent of body surface area. Female to male heart transplantation demonstrates coronary lumen enlargement. Purpose: To investigate relationships between endogenous androgens and coronary luminal size in women with suspected ischemic heart disease (IHD). Methods: We analyzed 69 women with available androgen levels. Results: Group mean age was 54 ± 10 years with 64 % post-menopausal. Lumen cross-sectional area (CSA) and external elastic membrane (EEM) CSA positively correlated with free testosterone (FT) (r = 0.29, p = 0.049; r = 0.29, p = 0.01), respectively, and negatively correlated with SHBG (r = -0.26, p = 0.03; r = -0.29, p = 0.02), respectively. Atheroma CSA positively correlated with FT (r = 0.24. p = 0.05). These correlations became non-significant after adjusting for waist circumference. Conclusions: In women with suspected ischemic heart disease, endogenous androgens, coronary atheroma and luminal size are related, and may be moderated by waist circumference.

Persistence and Adherence to PCSK9 Inhibitor Monoclonal Antibodies Versus Ezetimibe in Real-World Settings.

INTRODUCTION: The cardiovascular disease risk reduction benefits of proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies (PCSK9i mAb) and ezetimibe are dependent on remaining on treatment and being persistent and adherent. We estimated the percentage of patients on therapy, persistent and adherent at 182 and 365 days among US adults with health insurance who initiated a PCSK9i mAb (n = 16,588) or ezetimibe (n = 83,086) between July 2015 and December 2019. METHODS: Using pharmacy fill claims, being on therapy was defined as having a day of medication supply in the last 60 of 182 and 365 days following treatment initiation, being persistent was defined as not having a gap of 60 days or more between the last day of supply from one prescription fill and the next fill, and being adherent was defined by having medication available to take on ≥ 80% of the 182 and 365 days following treatment initiation. We estimated multivariable-adjusted risk ratios for being persistent and adherent comparing patients initiating PCSK9i mAb versus ezetimibe using Poisson regression. RESULTS: At 182 days following initiation, 80% and 68% were on therapy and 76% and 64% were persistent among patients who initiated a PCSK9i mAb and ezetimibe, respectively. Among patients who were on therapy and persistent at 182 days following initiation, 88% and 81% of those who initiated a PCSK9i mAb and ezetimibe, respectively, were on therapy at 365 days. Among those on therapy and persistent at 182 days following initiation, being persistent and being adherent at 365 days were each more common among PCSK9i mAb versus ezetimibe initiators (persistent: 82% versus 76%, multivariable-adjusted risk ratio 1.07; 95% confidence interval [CI] 1.06-1.08; adherent: 74% versus 71%, multivariable-adjusted risk ratio 1.02; 95% CI 1.01-1.03). CONCLUSIONS: These data suggest approaches to increase persistence and adherence to PCSK9i mAb and ezetimibe should be implemented prior to or within 182 days following treatment initiation.

Safety of the PCSK9 inhibitor alirocumab: insights from 47 296 patient-years of observation.

The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

New approaches to triglyceride reduction: Is there any hope left?

Triglycerides play a crucial role in the efficient storage of energy in the body. Mild and moderate hypertriglyceridemia (HTG) is a heterogeneous disorder with significant association with atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, ischemic stroke, and peripheral artery disease and represents an important component of the residual ASCVD risk in statin treated patients despite optimal low-density lipoprotein cholesterol reduction. Individuals with severe HTG (>1,000 mg/dL) rarely develop atherosclerosis but have an incremental incidence of acute pancreatitis with significant morbidity and mortality. HTG can occur from a combination of genetic (both mono and polygenic) and environmental factors including poor diet, low physical activity, obesity, medications, and diseases like insulin resistance and other endocrine pathologies. HTG represents a potential target for ASCVD risk and pancreatitis risk reduction, however data on ASCVD reduction by treating HTG is still lacking and HTG-associated acute pancreatitis occurs too rarely to effectively demonstrate treatment benefit. In this review, we address the key aspects of HTG pathophysiology and examine the mechanisms and background of current and emerging therapies in the management of HTG.

Elevated high-density lipoprotein cholesterol and adverse outcomes in women with symptoms of ischemic heart disease.

Background: Emerging data in the general population and those with coronary artery disease demonstrate higher risk of adverse outcomes with high (>70 mg/dL) HDL-C levels. There are limited data on the risk of adverse outcomes in women with suspected ischemic heart disease. Objective: To investigate relationships between high (>70 mg/dL), average (50-70 mg/dL), and low (<50 mg/dL) HDL-C levels with major adverse cardiac events (MACE) (death, myocardial infarction, stroke, and heart failure hospitalization), and all-cause mortality in women referred for coronary angiography for suspected myocardial ischemia. Methods: A total of 607 women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) original cohort (NCT00000554) with available HDL-C values were included in this analysis. Associations between HDL-C level and outcomes were evaluated using both multivariate Cox proportional hazard regression and spline regression analysis. Results: The mean age was 59 ± 12 years, 62 % had 3 or more cardiac risk factors, and 66 (10.9 %) had a high HDL-C. High and low HDL-C were both associated with higher MACE risk compared to average HDL-C after adjusting for demographic and clinical characteristics (HR 1.80, CI 1.03-3.14, p = 0.038; HR 1.63, CI 1.09-2.42, p = 0.016, respectively). Similarly, high, and low HDL-C were associated with higher risk of all-cause mortality (HR 3.64, CI 1.84-7.20, p < 0.001; HR 2.81, CI 1.67-4.71, p < 0.001, respectively). Conclusions: High and low HDL-C levels are both independently associated with higher MACE and all-cause mortality in women with suspected ischemia undergoing coronary angiography.

Relating Lipoprotein(a) Concentrations to Cardiovascular Event Risk After Acute Coronary Syndrome: A Comparison of 3 Tests.

BACKGROUND: Lipoprotein(a) is a risk factor for cardiovascular events and modifies the benefit of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. Lipoprotein(a) concentration can be measured with immunoassays reporting mass or molar concentration or a reference measurement system using mass spectrometry. Whether the relationships between lipoprotein(a) concentrations and cardiovascular events in a high-risk cohort differ across lipoprotein(a) methods is unknown. We compared the prognostic and predictive value of these types of lipoprotein(a) tests for major adverse cardiovascular events (MACE). METHODS: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the PCSK9 inhibitor alirocumab with placebo in patients with recent acute coronary syndrome. We compared risk of a MACE in the placebo group and MACE risk reduction with alirocumab according to baseline lipoprotein(a) concentration measured by Siemens N-latex nephelometric immunoassay (IA-mass; mg/dL), Roche Tina-Quant turbidimetric immunoassay (IA-molar; nmol/L), and a noncommercial mass spectrometry-based test (MS; nmol/L). Lipoprotein(a) values were transformed into percentiles for comparative modeling. Natural cubic splines estimated continuous relationships between baseline lipoprotein(a) and outcomes in each treatment group. Event rates were also determined across baseline lipoprotein(a) quartiles defined by each assay. RESULTS: Among 11 970 trial participants with results from all 3 tests, baseline median (Q1, Q3) lipoprotein(a) concentrations were 21.8 (6.9, 60.0) mg/dL, 45.0 (13.2, 153.8) nmol/L, and 42.2 (14.3, 143.1) nmol/L for IA-mass, IA-molar, and MS, respectively. The strongest correlation was between IA-molar and MS (r=0.990), with nominally weaker correlations between IA-mass and MS (r=0.967) and IA-mass and IA-molar (r=0.972). Relationships of lipoprotein(a) with MACE risk in the placebo group were nearly identical with each test, with estimated cumulative incidences differing by ≤0.4% across lipoprotein(a) percentiles, and all were incrementally prognostic after accounting for low-density lipoprotein cholesterol levels (all spline P≤0.0003). Predicted alirocumab treatment effects were also nearly identical for each of the 3 tests, with estimated treatment hazard ratios differing by ≤0.07 between tests across percentiles and nominally less relative risk reduction by alirocumab at lower percentiles for all 3 tests. Absolute risk reduction with alirocumab increased with increasing lipoprotein(a) measured by each test, with significant linear trends across quartiles. CONCLUSIONS: In patients with recent acute coronary syndrome, 3 lipoprotein(a) tests were similarly prognostic for MACE in the placebo group and predictive of MACE reductions with alirocumab at the cohort level. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01663402.

Association between P-pulmonale and respiratory morbidity in COPD: a secondary analysis of the BLOCK-COPD trial.

RATIONALE: Pulmonary hypertension (PH) in COPD confers increased risk of exacerbations (ECOPD). Electrocardiogram (ECG) indicators of PH are prognostic both in PH and COPD. In the Beta-Blockers for the Prevention of Acute Exacerbations of COPD (BLOCK-COPD) trial, metoprolol increased risk of severe ECOPD through unclear mechanisms. OBJECTIVE: We evaluated whether an ECG indicator of PH, P-pulmonale, would be associated with ECOPD and whether participants with P-pulmonale randomized to metoprolol were at higher risk of ECOPD and worsened respiratory symptoms given the potential detrimental effects of beta-blockers in PH. METHODS: ECGs of 501 participants were analyzed for P-pulmonale (P wave enlargement in lead II). Cox proportional hazards models evaluated for associations between P-pulmonale and time to ECOPD (all and severe) for all participants and by treatment assignment (metoprolol vs. placebo). Linear mixed-effects models evaluated the association between treatment assignment and P-pulmonale on change in symptom scores (measured by CAT and SOBQ). RESULTS: We identified no association between P-pulmonale and risk of any ECOPD or severe ECOPD. However, in individuals with P-pulmonale, metoprolol was associated with increased risk for ECOPD (aHR 2.92, 95% CI: 1.45-5.85). There was no association between metoprolol and ECOPD in individuals without P-pulmonale (aHR 1.01, 95% CI: 0.77-1.31). Individuals with P-pulmonale assigned to metoprolol experienced worsening symptoms (mean increase of 3.95, 95% CI: 1.32-6.58) whereas those assigned to placebo experienced a mean improvement in CAT score of -2.45 (95% CI: -0.30- -4.61). CONCLUSIONS: In individuals with P-pulmonale, metoprolol was associated with increased exacerbation risk and worsened symptoms. These findings may explain the findings observed in BLOCK-COPD.

Lipoprotein(a) and the Risk for Recurrent Atherosclerotic Cardiovascular Events Among Adults With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & Objective: Many adults with chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD) have high lipoprotein(a) levels. It is unclear whether high lipoprotein(a) levels confer an increased risk for recurrent ASCVD events in this population. We estimated the risk for recurrent ASCVD events associated with lipoprotein(a) in adults with CKD and prevalent ASCVD. Study Design: Observational cohort study. Setting & Participants: We included 1,439 adults with CKD and prevalent ASCVD not on dialysis enrolled in the Chronic Renal Insufficiency Cohort study between 2003 and 2008. Exposure: Baseline lipoprotein(a) mass concentration, measured using a latex-enhanced immunoturbidimetric assay. Outcomes: Recurrent ASCVD events (primary outcome), kidney failure, and death (exploratory outcomes) through 2019. Analytical Approach: We used Cox proportional-hazards regression models to estimate adjusted HR (aHRs) and 95% CIs. Results: Among participants included in the current analysis (mean age 61.6 years, median lipoprotein(a) 29.4 mg/dL [25th-75th percentiles 9.9-70.9 mg/dL]), 641 had a recurrent ASCVD event, 510 developed kidney failure, and 845 died over a median follow-up of 6.6 years. The aHR for ASCVD events associated with 1 standard deviation (SD) higher log-transformed lipoprotein(a) was 1.04 (95% CI, 0.95-1.15). In subgroup analyses, 1 SD higher log-lipoprotein(a) was associated with an increased risk for ASCVD events in participants without diabetes (aHR, 1.23; 95% CI, 1.02-1.48), but there was no evidence of an association among those with diabetes (aHR, 0.99; 95% CI, 0.88-1.10, P comparing aHRs = 0.031). The aHR associated with 1 SD higher log-lipoprotein(a) in the overall study population was 1.16 (95% CI, 1.04-1.28) for kidney failure and 1.02 (95% CI, 0.94-1.11) for death. Limitations: Lipoprotein(a) was not available in molar concentration. Conclusions: Lipoprotein(a) was not associated with the risk for recurrent ASCVD events in adults with CKD, although it was associated with a risk for kidney failure.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Incident CHD and ischemic stroke associated with lipoprotein(a) by levels of Factor VIII and inflammation.

BACKGROUND: Inflammation and coagulation may contribute to the increased risk for atherosclerotic cardiovascular disease (ASCVD) associated with high lipoprotein(a). The association of lipoprotein(a) with ASCVD is stronger in individuals with high versus low high-sensitivity C-reactive protein (hs-CRP), a marker of inflammation. OBJECTIVES: Determine the association of lipoprotein(a) with incident ASCVD by levels of coagulation Factor VIII controlling for hs-CRP. METHODS: We analyzed data from 6,495 men and women 45 to 84 years of age in the Multi-Ethnic Study of Atherosclerosis (MESA) without prevalent ASCVD at baseline (2000-2002). Lipoprotein(a) mass concentration, Factor VIII coagulant activity, and hs-CRP were measured at baseline and categorized as high or low (≥75th or <75th percentile of the distribution). Participants were followed for incident coronary heart disease (CHD) and ischemic stroke through 2015. RESULTS: Over a median follow-up of 13.9 years, there were 390 CHD and 247 ischemic stroke events. The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) (≥40.1 versus <40.1 mg/dL) including adjustment for hs-CRP among participants with low and high Factor VIII was 1.07 (0.80-1.44) and 2.00 (1.33-3.01), respectively (p-value for interaction 0.016). The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) including adjustment for Factor VIII was 1.16 (0.87-1.54) and 2.00 (1.29-3.09) among participants with low and high hs-CRP, respectively (p-value for interaction 0.042). Lp(a) was not associated with ischemic stroke regardless of Factor VIII or hs-CRP levels. CONCLUSION: High lipoprotein(a) is a risk factor for CHD in adults with high levels of hemostatic or inflammatory markers.