The handedness of the cell regulates the permeability of blood vessels.

The strong association between lipoprotein (a) [Lp(a)] and atherosclerotic cardiovascular disease has led to considerations of Lp(a) being a potential target for mitigating residual cardiovascular risk. While approximately 20 % of the population has an Lp(a) level greater than 50 mg/dL, there are no currently available pharmacological lipid-lowering therapies that have demonstrated substantial reduction in Lp(a). Novel therapies to lower Lp(a) include antisense oligonucleotides and small-interfering ribonucleic acid molecules and have shown promising results in phase 2 trials. Phase 3 trials are currently underway and will test the causal relationship between Lp(a) and ASCVD and whether lowering Lp(a) reduces cardiovascular outcomes. In this review, we summarize emerging insights related to Lp(a)’s role as a risk-enhancing factor for ASCVD, association with calcific aortic stenosis, effects of existing therapies on Lp(a) levels, and variations amongst patient populations. The evolving therapeutic landscape of emerging therapeutics is further discussed.

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.

Chest pain is a common concern of women evaluated in both the inpatient and outpatient setting. There are significant differences in pathophysiology when comparing coronary artery disease (CAD) in women and men, including a higher prevalence of nonobstructive CAD. Furthermore, significant sex disparities exist in the care of women with acute coronary syndromes that stem from factors such as delays in diagnosis and inconsistencies in treatment. The 2021 AHA/ACC/Multisociety Guideline for the Evaluation and Diagnosis of Chest pain is an important document comprised of recommendations for the assessment of acute and stable chest pain. In this review, we discuss key points from the guideline in the context of evaluating chest pain in women. We discuss the similarities and differences of chest pain presentation between the sexes, evaluation of chest pain in patients with known nonobstructive CAD and ischemia with no obstructive coronary arteries, and considerations for cardiac imaging during pregnancy.

Background: Sex‐based differences in the association of lipoprotein(a) with cardiovascular outcomes have not been well established for those without prior atherosclerotic cardiovascular disease. Methods and Results: Patients with no baseline atherosclerotic cardiovascular disease were identified in the MGB (Mass General Brigham) Lp(a) Registry, a retrospective cohort of patients who had lipoprotein(a) measured from 2000 to 2019. Lipoprotein(a) percentile groups were categorized as 1st to 50th (reference), 51st to 70th, 71st to 90th, and 91st to 100th. The primary outcome was a composite of fatal or nonfatal myocardial infarction, or fatal or nonfatal ischemic stroke. Cox proportional hazard modeling was used to assess the association of lipoprotein(a) with the primary outcome. Among 6238 patients with no baseline atherosclerotic cardiovascular disease, 45% were women. Women had higher total cholesterol, low‐density lipoprotein cholesterol, and median lipoprotein(a) (33.2 versus 28.9 nmol/L; P <0.001), whereas men had higher rates of diabetes and atrial fibrillation. Higher lipoprotein(a) was associated with an increased incidence of the primary composite outcome, with patients in the 91st to 100th percentile group (≥216 nmol/L) having an adjusted hazard ratio (HR) of 2.07 (95% CI, 1.31–3.25; P <0.01) in women and 2.39 (95% CI, 1.57–3.65; P <0.01) in men, with no interaction based on sex. When examining individual outcomes, the strongest association was present between lipoprotein(a) and fatal or nonfatal myocardial infarction (women: adjusted HR, 2.61 [95% CI, 1.48–4.61]; men: adjusted HR, 3.36 [95% CI, 2.01–5.60]). When stratifying by age, female sex was associated with a lower risk of fatal or nonfatal myocardial infarction in those aged <60 years; however, among older individuals, the risk conferred by elevated lipoprotein(a) was similar between men and women. Conclusions: Among individuals with no prior atherosclerotic cardiovascular disease, elevated lipoprotein(a) is associated with higher rates of cardiovascular outcomes, particularly myocardial infarction, in both women and men.