As the clinical applications of immune checkpoint inhibitors (ICIs) expand, our knowledge of the potential adverse effects of these drugs continues to broaden. Emerging evidence supports the association between ICI therapy with accelerated atherosclerosis and atherosclerotic cardiovascular (CV) events. We discuss the biological plausibility and the clinical evidence supporting an effect of inhibition of these immune checkpoints on atherosclerotic CV disease. Further, we provide a perspective on potential diagnostic and pharmacological strategies to reduce atherosclerotic risk in ICI-treated patients. Our understanding of the pathophysiology of ICI-related atherosclerosis is in its early stages. Further research is needed to identify the mechanisms linking ICI therapy to atherosclerosis, leverage the insight that ICI therapy provides into CV biology, and develop robust approaches to manage the expanding cohort of patients who may be at risk for atherosclerotic CV disease.

Risk assessment is a fundamental step in the current approach to primary prevention of atherosclerotic cardiovascular disease (ASCVD). When considering pharmacotherapy for primary prevention of ASCVD, current prevention guidelines in the United States recommend the use of the pooled cohort equations (PCE) to assess 10-year ASCVD risk and begin the important process of shared decision-making between patients and clinicians. Clinicians should support patients in the decisionmaking process by turning raw data into information that is easily understood and more effectively utilized for decisions around the treatment plan. In this work, we present a tool to help patients visualize ASCVD risk and the projected impact of risk-lowering interventions. We believe this visual tool can facilitate communication of ASCVD risk to patients, and improve patient understanding of risk and the potential impact of risklowering interventions, which we believe may help patients make more informed, empowered decisions that achieve greater risk reduction.

This case report describes a 67-year-old African-American woman with homozygous familial hypercholesterolemia caused by 2 pathogenic variants in the LDLR gene. Initial surgical, pharmacological, and low-density lipoprotein apheresis interventions were insufficient; the addition of proprotein convertase subtilisin-kexin type 9 and angiopoietin-like 3 inhibitors lowered her low-density lipoprotein cholesterol to <70 mg/dL. (Level of Difficulty: Advanced.).

Elevated concentration of lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease, including coronary artery disease, stroke, peripheral artery disease, and so on. Emerging data suggest that Lp(a) contributes to the increased risk for cardiovascular events even in the setting of effective reduction of plasma low-density lipoprotein cholesterol. Nevertheless, puzzling issues exist covering potential genetic factors, Lp(a) assay, possible individuals for analysis, a cutoff point of increased risk, and clinical interventions. In the Chinese population, Lp(a) exhibited a distinctive prevalence and regulated various cardiovascular diseases in specific ways. Hence, it is valuable to clarify the role of Lp(a) in cardiovascular diseases and explore prevention and control measures for the increase in Lp(a) prevalence in the Chinese population. This Beijing Heart Society experts\' scientific statement will present the detailed knowledge concerning Lp(a)-related studies combined with Chinese population observations to provide the key points of reference.

Aspirin has been a cornerstone for primary prevention of cardiovascular disease for decades, however its use in primary prevention has been challenged in recent years. The 2022 USPSTF guidelines lowered the recommendation for the use of aspirin in primary prevention based on the recent trials that demonstrated a low to neutral benefit and an increased bleeding risk with the use of aspirin in primary prevention. However, these trials enrolled patients at a relatively low risk for atherosclerotic cardiovascular disease (ASCVD) and higher bleeding risk which could have contributed to the negative results of the trials. ASCVD prevention is ideal when therapies are personalized based on individual risk. Coronary artery calcium (CAC) score is a robust marker of atherosclerosis and reliably predicts the ASCVD risk in a graded fashion. Several studies have demonstrated the use of a CAC≥100 to identify patients who will benefit from the use of aspirin in primary prevention. Furthermore, a CAC=0 identifies patients in whom aspirin would lead to net harm. In the continuum of risk from primary to secondary prevention, CAC is likely to identify the level of risk that warrants aspirin use in patients with subclinical ASCVD. The ACC/AHA 2019 primary prevention guidelines recommend the use of CAC to reclassify risk and guide personalized allocation of statins and aspirin. Although the USPSTF has not endorsed the use of CAC in the past, given an extensive body of evidence for use of CAC to guide primary preventive therapies including aspirin, it seems reasonable to use CAC to identify the level of plaque burden at which the benefit of aspirin outweighs its risk in clinical practice and personalize theallocation of aspirin in primary prevention. Future studies and randomized trials assessing the role of preventive therapies should use CAC score for risk stratification.

Approximately one-half of the phenotypic susceptibility to atherosclerotic cardiovascular disease (ASCVD) has a genetic basis. Although individual allelic variants generally impart a small effect on risk for ASCVD, an emerging body of data has shown that the aggregation and weighting of many of these genetic variations into \"scores\" can further discriminate an individual\'s risk beyond traditional risk factors alone. Consistent with the theory of population genetics, such polygenic risk scores (PRS) appear to be ethnicity specific because their elements comprise single-nucleotide variants that are always ethnicity specific. The currently available PRS are derived predominantly from European ancestry and thus predictably perform less well among non-European participants, a fact that has implications for their use in the Asia-Pacific region. This paper describes the current state of knowledge of PRS, the available data that support their use in this region, and highlights the needs moving forward to safely and effectively implement them in clinical care in the Asia-Pacific region.

Compound heterozygous familial hypercholesterolemia patients are phenotypically similar to homozygous familial hypercholesterolemia patients, present with significant elevations of low-density lipoprotein cholesterol, and are at risk of cardiovascular disease. Although new treatment options are emerging, the stepwise approach to the use of different therapies has not been well described. (Level of Difficulty: Intermediate.).

UNASSIGNED: Contemporary prevalence, awareness, and control of severe hypercholesterolemia (SH) and familial hypercholesterolemia (FH) and the associated atherosclerotic cardiovascular disease risk in the US are unknown.
UNASSIGNED: Using electronic health records, we assessed the burden of SH and FH in Olmsted County, Minnesota, US, between 2004 and 2015. We defined SH as low-density lipoprotein cholesterol (LDL-C) level ≥190 mg/dl without secondary causes of hypercholesterolemia and FH as a Dutch Lipid Clinic Network score ≥6. Controls were age- and sex-matched individuals with LDL-C level <190 mg/dl.
UNASSIGNED: The age- and sex-adjusted point and period prevalence (age-recursive method) of SH was 4.44% and 8.95%, respectively; 1 in 21 had FH (∼1:233 adults), and 46.2% had a recorded diagnosis. Guideline recommended targets (LDL-C <100 mg/dl and <70 mg/dl in the primary and secondary prevention settings, respectively) were achieved in 33.1% and 21.2% of SH cases, with less women overall achieving the target than men (18.6% vs. 23.7%, p=0.022). After adjustment for conventional risk factors, the hazard ratio for incident coronary heart disease (CHD) in those with SH was 1.21 (1.05-1.39; p=0.010), in those with SH and a family history of CHD was 2.16 (1.57-2.96; p<0.001) and in those with FH was 4.61 (2.66-7.97; p<0.001). The association of SH with CHD was modified by age (p-interaction = 0.015), such that the risk was greater at younger ages.
UNASSIGNED: SH was prevalent and an independent risk factor for incident CHD. Awareness and control were low, highlighting a treatment gap (more prominent in women) that needs to be addressed.

UNASSIGNED: To characterize the utility of an existing electrocardiogram (ECG)-artificial intelligence (AI) algorithm of left ventricular dysfunction (LVD) in immune-mediated necrotizing myopathy (IMNM).
UNASSIGNED: A retrospective cohort observational study was conducted within our tertiary-care neuromuscular clinic for patients with IMNM meeting European Neuromuscular Centre diagnostic criteria (January 1, 2000, to December 31, 2020). A validated AI algorithm using 12-lead standard ECGs to detect LVD was applied. The output was presented as a percent probability of LVD. Electrocardiograms before and while on immunotherapy were reviewed. The LVD-predicted probability scores were compared with echocardiograms, immunotherapy treatment response, and mortality.
UNASSIGNED: The ECG-AI algorithm had acceptable accuracy in LVD prediction in 74% (68 of 89) of patients with IMNM with available echocardiograms (discrimination threshold, 0.74; 95% CI, 0.6-0.87). This translates into a sensitivity of 80.0% and specificity of 62.8% to detect LVD. Best cutoff probability prediction was 7 times more likely to have LVD (odds ratio, 6.75; 95% CI, 2.11-21.51; P=.001). Early detection occurred in 18% (16 of 89) of patients who initially had normal echocardiograms and were without cardiorespiratory symptoms, of which 6 subsequently advanced to LVD cardiorespiratory failure. The LVD probability scores improved for patients on immunotherapy (median slope, -3.96; R = -0.12; P=.002). Mortality risk was 7 times greater with abnormal LVD probability scores (hazard ratio, 7.33; 95% CI, 1.63-32.88; P=.009).
UNASSIGNED: In IMNM, an AI-ECG algorithm assists detection of LVD, enhancing the decision to advance to echocardiogram testing, while also informing on mortality risk, which is important in the decision of immunotherapy escalation and monitoring.

Atherosclerotic cardiovascular disease (ASCVD) is epidemic throughout the world and is etiologic for such acute cardiovascular events as myocardial infarction, ischemic stroke, unstable angina, and death. ASCVD also impacts risk for dementia, chronic kidney disease peripheral arterial disease and mobility, impaired sexual response, and a host of other visceral impairments that adversely impact the quality and rate of progression of aging. The relationship between low-density lipoprotein cholesterol (LDL-C) and risk for ASCVD is one of the most highly established and investigated issues in the entirety of modern medicine. Elevated LDL-C is a necessary condition for atherogenesis induction. Basic scientific investigation, prospective longitudinal cohorts, and randomized clinical trials have all validated this association. Yet despite the enormous number of clinical trials which support the need for reducing the burden of atherogenic lipoprotein in blood, the percentage of high and very high-risk patients who achieve risk stratified LDL-C target reductions is low and has remained low for the last thirty years. Atherosclerosis is a preventable disease. As clinicians, the time has come for us to take primordial and primary prevention more serously. Despite a plethora of therapeutic approaches, the large majority of patients at risk for ASCVD are poorly or inadequately treated, leaving them vulnerable to disease progression, acute cardiovascular events, and poor aging due to loss of function in multiple visceral organs. Herein we discuss the need to greatly intensify efforts to reduce risk, decrease disease burden, and provide more comprehensive and earlier risk assessment to optimally prevent ASCVD and its complications. Evidence is presented to support that treatment should aim for far lower goals in cholesterol management, should take into account many more factors than commonly employed today and should begin significantly earlier in life.