Association of Lipoprotein(a) With Major Adverse Cardiovascular Events Across hs-CRP: A Systematic Review and Meta-Analysis.

Background: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. The relationship between Lp(a) and major adverse cardiovascular events (MACE) in the context of high-sensitivity C-reactive protein (hs-CRP) levels remains controversial due to conflicting results from previous studies.

Objectives: This systematic review and meta-analysis aimed to clarify the association between Lp(a) and risk of MACE across different hs-CRP levels in both primary and secondary prevention settings.

Integrative proteomic analyses across common cardiac diseases yield mechanistic insights and enhanced prediction.

Cardiac diseases represent common highly morbid conditions for which molecular mechanisms remain incompletely understood. Here we report the analysis of 1,459 protein measurements in 44,313 UK Biobank participants to characterize the circulating proteome associated with incident coronary artery disease, heart failure, atrial fibrillation and aortic stenosis. Multivariable-adjusted Cox regression identified 820 protein-disease associations-including 441 proteins-at Bonferroni-adjusted P < 8.

Distinct Genetic Risk Profile in Aortic Stenosis Compared With Coronary Artery Disease.

Importance: Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist. However, it is unknown which genetic and cardiovascular risk factors might be AS-specific and which could be shared between AS and CAD.

Objective: To identify genetic risk loci and cardiovascular risk factors with AS-specific associations.

Clonal hematopoiesis and atherosclerosis.

Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a previously unrecognized, potent, age-related, and common risk factor for atherosclerosis. Somatic mutations in certain known leukemia driver genes give rise to clones of mutant cells in peripheral blood. The increased risk of developing hematologic malignancy does not, on its own, explain excess mortality in individuals with CHIP.

Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets: A Scientific Statement From the American Heart Association.

Valvular heart disease is a common cause of morbidity and mortality worldwide and has no effective medical therapy. Severe disease is managed with valve replacement procedures, which entail high health care-related costs and postprocedural morbidity and mortality. Robust ongoing research programs have elucidated many important molecular pathways contributing to primary valvular heart disease.

Major Facilitator Superfamily Domain Containing 5 Inhibition Reduces Lipoprotein(a) Uptake and Calcification in Valvular Heart Disease.

Background: High circulating levels of Lp(a) (lipoprotein[a]) increase the risk of atherosclerosis and calcific aortic valve disease, affecting millions of patients worldwide. Although atherosclerosis is commonly treated with low-density lipoprotein-targeting therapies, these do not reduce Lp(a) or risk of calcific aortic valve disease, which has no available drug therapies. Targeting Lp(a) production and catabolism may provide therapeutic benefit, but little is known about Lp(a) cellular uptake.

Multiancestry Genome-Wide Association Study of Aortic Stenosis Identifies Multiple Novel Loci in the Million Veteran Program.

Background: Calcific aortic stenosis (CAS) is the most common valvular heart disease in older adults and has no effective preventive therapies. Genome-wide association studies (GWAS) can identify genes influencing disease and may help prioritize therapeutic targets for CAS.

Methods: We performed a GWAS and gene association study of 14 451 patients with CAS and 398 544 controls in the Million Veteran Program.

Plasma biomarkers associated with adverse outcomes in patients with calcific aortic stenosis.

Aims: Enhanced risk stratification of patients with aortic stenosis (AS) is necessary to identify patients at high risk for adverse outcomes, and may allow for better management of patient subgroups at high risk of myocardial damage. The objective of this study was to identify plasma biomarkers and multimarker profiles associated with adverse outcomes in AS.

Methods And Results: We studied 708 patients with calcific AS and measured 49 biomarkers using a Luminex platform.

The impact of removing former drinkers from genome-wide association studies of AUDIT-C.

Background And Aims: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire screens for harmful drinking using a 12-month timeframe. A score of 0 is assigned to individuals who report abstaining from alcohol in the past year. However, many middle-age individuals reporting current abstinence are former drinkers (FDs).

PCSK9 loss of function is protective against extra-coronary atherosclerotic cardiovascular disease in a large multi-ethnic cohort.

Background: Therapeutic inhibition of PCSK9 protects against coronary artery disease (CAD) and ischemic stroke (IS). The impact on other diseases remains less well characterized.

Methods: We created a genetic risk score (GRS) for PCSK9 using four single nucleotide polymorphisms (SNPs) at or near the PCSK9 locus known to impact lower LDL-Cholesterol (LDL-C): rs11583680, rs11591147, rs2479409, and rs11206510.

Mendelian Randomization Analysis of Hemostatic Factors and Their Contribution to Peripheral Artery Disease-Brief Report.

Background And Objective: Peripheral artery disease (PAD) is the third most common form of atherosclerotic vascular disease and is characterized by significant functional disability and increased cardiovascular mortality. Recent genetic data support a role for a procoagulation protein variant, the factor V Leiden mutation, in PAD. The role of other hemostatic factors in PAD remains unknown.

Phenome-wide association analysis suggests the APOL1 linked disease spectrum primarily drives kidney-specific pathways.

The relationship between commonly occurring genetic variants (G1 and G2) in the APOL1 gene in African Americans and different disease traits, such as kidney disease, cardiovascular disease, and pre-eclampsia, remains the subject of controversy. Here we took a genotype-first approach, a phenome-wide association study, to define the spectrum of phenotypes associated with APOL1 high-risk variants in 1,837 African American participants of Penn Medicine Biobank and 4,742 African American participants of Vanderbilt BioVU. In the Penn Medicine Biobank, outpatient creatinine measurement-based estimated glomerular filtration rate and multivariable regression models were used to evaluate the association between high-risk APOL1 status and renal outcomes.

Case contamination in electronic health records based case-control studies.

Clinically relevant information from electronic health records (EHRs) permits derivation of a rich collection of phenotypes. Unlike traditionally designed studies where scientific hypotheses are specified a priori before data collection, the true phenotype status of any given individual in EHR-based studies is not directly available. Structured and unstructured data elements need to be queried through preconstructed rules to identify case and control groups.

Circulating and tissue matricellular RNA and protein expression in calcific aortic valve disease.

Aortic valve sclerosis is a highly prevalent, poorly characterized asymptomatic manifestation of calcific aortic valve disease and may represent a therapeutic target for disease mitigation. Human aortic valve cusps and blood were obtained from 333 patients undergoing cardiac surgery ( = 236 for severe aortic stenosis, = 35 for asymptomatic aortic valve sclerosis, = 62 for no valvular disease), and a multiplex assay was used to evaluate protein expression across the spectrum of calcific aortic valve disease. A subset of six valvular tissue samples ( = 3 for asymptomatic aortic valve sclerosis, = 3 for severe aortic stenosis) was used to create RNA sequencing profiles, which were subsequently organized into clinically relevant gene modules.