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Bishnu H Subedi,1,2 Parag H Joshi,1 Steven R Jones,1 Seth S Martin,1 Michael J Blaha,1 Erin D Michos1 1Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 2Greater Baltimore Medical Center, Baltimore, MD, USA Abstract: Many studies have suggested that a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) is low high-density lipoprotein cholesterol (HDL-C). Therefore, increasing HDL-C with therapeutic agents has been considered an attractive strategy. In the prestatin era, fibrates and niacin monotherapy, which cause modest increases in HDL-C, reduced ASCVD events. Since their introduction, statins have become the cornerstone of lipoprotein therapy, the benefits of which are primarily attributed to decrease in low-density lipoprotein cholesterol. Findings from several randomized trials involving niacin or cholesteryl ester transfer protein inhibitors have challenged the concept that a quantitative elevation of plasma HDL-C will uniformly translate into ASCVD benefits. Consequently, the HDL, or more correctly, HDL-C hypothesis has become more controversial. There are no clear guidelines thus far for targeting HDL-C or HDL due to lack of solid outcomes data for HDL specific therapies. HDL-C levels are only one marker of HDL out of its several structural or functional properties. Novel approaches are ongoing in developing and assessing agents that closely mimic the structure of natural HDL or replicate its various functions, for example, reverse cholesterol transport, vasodilation, anti-inflammation, or inhibition of platelet aggregation. Potential new approaches like HDL infusions, delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics, and gene therapy are in early phase trials. This review will outline current therapies and describe future directions for HDL therapeutics. Keywords: high-density lipoprotein, lipids, cholesterol, atherosclerosis, cardiovascular disease, therapy

Background: Cardiovascular calcification outside of the coronary tree, known as extracoronary calcification (ECC), is highly prevalent, often occurs concurrently in multiple sites, and yet its prognostic value is unclear. Objective: To determine whether multisite ECC is associated with coronary heart disease (CHD) events, CHD mortality, and all-cause mortality. Methods: We evaluated 5903 participants from the Multi-Ethnic Study of Atherosclerosis without diabetes who underwent CT imaging for calcification of the aortic valve, aortic root, mitral valve, and thoracic aorta. Participants were followed for 10.3 years. Multivariable adjusted hazard ratios estimated risk of outcomes for increasing numbers of ECC sites (0, 1, 2, 3, and 4), and receiver operator characteristic analysis assessed model discrimination. Results: Prevalence of any ECC was 45%; median age was 62 years. Compared with those without ECC, those with ECC in 4 sites had increased hazards of 4.5, 7.1 and 2.3 for CHD events, CHD mortality, and all-cause mortality, respectively, independent of traditional risk factors (TRF; all P ≤.05), and had ≥2-fold increased hazards for outcomes independent of coronary artery calcification (CAC). Each additional site of ECC was positively associated with each outcome in a graded fashion. When added to TRF, ECC significantly increased the area under the receiver operator characteristic curve for all outcomes and modestly increased the area under the curve for mortality beyond TRF + CAC (0.799 to 0.802; P =03). Conclusion: Increasing multisite ECC has a graded association with higher CHD and mortality risk, contributing information beyond TRF. Multisite ECC incidentally identified on imaging can be used to improve individualized risk prediction.

We hypothesized that anthropometric measures of abdominal obesity would have a stronger positive association with nonalcoholic fatty liver disease (NAFLD) measured by noncontrast computed tomography versus general measures of obesity. The Multiethnic Study of Atherosclerosis comprised participants aged 45 to 84 years free of known cardiovascular disease. We studied 4,088 participants with adequate liver and spleen computed tomography imaging and no previous use of oral steroids, class 3 antiarrhythmics, moderately heavy alcohol use, or cirrhosis. Prevalent NAFLD was defined as a liver:spleen Hounsfield attenuation ratio of

OBJECTIVE We compared South Asians with four other racial/ethnic groups in the U.S. to determine whether sociodemographic, lifestyle, or metabolic factors could explain the higher diabetes prevalence and whether insulin resistance and b-cell dysfunction oc

Patients with obstructive sleep apnea (OSA) have a high burden of cardiovascular disease (CVD) but a causal relationship between OSA and atherosclerotic CVD remains unclear. We systematically reviewed the literature analyzing the relationship. A review of the Medline database for studies noninvasively evaluating subclinical CVD in OSA was conducted. A total of fifty-two studies were included in this review.Across the studies the prevalence of atherosclerosis, as assessed by coronary artery calcification, carotid intima-media thickness, brachial artery flow-mediated dilation and pulse wave velocity was higher in patients with OSA and correlated with increasing severity and duration of OSA.This study shows OSA is an independent predictor of subclinical CVD as CVD is more likely to occur in patients with long standing and severe OSA. Further research is however necessary to identify specific OSA populations that would benefit from aggressive screening.

Cardiovascular imaging modalities such as coronary computed tomography, carotid ultrasonography, and cardiovascular magnetic resonance imaging are increasingly being used to measure cardiovascular disease progression. Imaging measures, most notably carotid intima-media thickness (CIMT), are being applied as surrogate markers for clinical end points such as myocardial infarction and death in clinical trials. Clinicians and their patients are faced with the challenge of evaluating these imaging measures for their efficacy and practicality in clinical practice, as well as in clinical trials. The investigators determined from a review of clinical trials and guidelines that CIMT measurement may be useful in evaluating cardiovascular disease risk in select patient populations but may not always be an appropriate surrogate for clinical end points. In conclusion, although CIMT has clear advantages over alternative cardiovascular imaging modalities, ultimately, prospective trials comparing the effectiveness of CIMT as a predictive tool of cardiovascular risk with that of other novel markers would best direct clinical recommendations for this imaging measure. [ABSTRACT FROM AUTHOR]

Objective: It is unclear whether coronary artery calcium (CAC) is effective for risk stratifying patients with diabetes in whom treatment decisions are uncertain.Research Design and Methods: Of 44,052 asymptomatic individuals referred for CAC testing, we studied 2,384 individuals with diabetes. Subjects were followed for a mean of 5.6 ± 2.6 years for the end point of all-cause mortality.Results: There were 162 deaths (6.8%) in the population. CAC was a strong predictor of mortality across age-groups (age <50, 50-59, ≥60), sex, and risk factor burden (0 vs. ≥1 additional risk factor). In individuals without a clear indication for aspirin per current guidelines, CAC stratified risk, identifying patients above and below the 10% risk threshold of presumed aspirin benefit.Conclusions: CAC can help risk stratify individuals with diabetes and may aid in selection of patients who may benefit from therapies such as low-dose aspirin for primary prevention. [ABSTRACT FROM AUTHOR]

Objective: We sought to determine whether insulin resistance predicts the incidence and progression of coronary artery calcification (CAC).Research Design and Methods: We studied 5,464 participants not on hypoglycemic therapy from the Multi-Ethnic Study of Atherosclerosis (MESA). Each had baseline homeostasis model assessment of insulin resistance (HOMA-IR) and baseline and follow-up CAC scores. Incident CAC was defined as newly detectable CAC; progression was defined as advancing CAC volume score at follow-up.Results: Median HOMA-IR was 1.2 (0.8-2.0). Across all ethnicities, there was a graded increase in CAC incidence and progression with increasing HOMA-IR. When compared with those in the 1st quartile, participants in the 2nd-4th quartiles had 1.2, 1.5, and 1.8 times greater risk of developing CAC. Median annualized CAC score progression was 8, 14, and 17 higher, respectively. However, HOMA-IR was not predictive after adjustment for metabolic syndrome components.Conclusions: HOMA-IR predicts CAC incidence and progression, but not independently of metabolic syndrome. [ABSTRACT FROM AUTHOR]

This cross-sectional study included 18,797 participants from six longitudinal cohorts (CARDIA, FHS Gen III, HCHS/SOL, MESA, MiHeart, and REGARDS). 5,806 of them were with high-sensitivity C-reactive protein (hs-CRP) measurements. We found that among exclusive electronic cigarette (EC) use was associated with significantly lower high-sensitivity C-reactive protein (hs-CRP) levels compared to exclusive combustible cigarette use, suggesting a potentially lower inflammatory burden. hs-CRP levels in dual users and former smokers currently using EC were comparable to those observed in exclusive cigarette smokers. In contrast, individuals who exclusively used ECs showed no significant difference in hs-CRP levels compared to never smokers. These findings have important implications for tobacco regulation, public health, and clinical practice, highlighting the need for continued monitoring of EC-related health impacts., Competing Interests: Declaration of competing interest The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Colchicine has emerged as an effective agent for reducing ASCVD based on recent large cardiovascular outcome trials and exerts its benefit through targeting inflammation. In light of the robust body of data and FDA approval of low-dose colchicine for ASCVD prevention, this paper aimed to use the National Prescription Audie to quantify the volume and trends of colchicine prescriptions dispensed rough U.S. retail pharmacies between March 2018 and February 2024. Despite a 6% increase in total monthly prescriptions since 2020, driven primarily by cardiologists, this specialty still represents only 2.8-4% of the national monthly totals with small absolute numbers (i.e. estimated ∼4000 incremental prescriptions/month since 2020), suggesting limited cardiologist adoption of colchicine for ASCVD prevention despite favorable clinical trial data., Competing Interests: Declaration of competing interest Michael Blaha reports grants from the National Institutes of Health, US Food and Drug Administration, American Heart Association; grants and personal fees from Amgen, Bayer, and Novo Nordisk, and personal fees from Novartis, Roche, Merck, Boehringer Ingelheim, Vectura, Agepha, Astra Zeneca, Eli Lilly, and New Amsterdam outside the submitted work. Dr. Alexander is past Chair of FDA's Peripheral and Central Nervous System Advisory Committee and is a co-founding Principal and equity holder in Stage Analytics. These arrangements have been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies. Erfan Tasdighi has received support from the NIH (grant T32 HL007227). No other disclosures for other authors are reported., (Copyright © 2024. Published by Elsevier Inc.)

Purpose of Review: To review the current evidence and highlight future strategies regarding consideration of coronary artery calcium (CAC) density in cardiovascular disease (CVD) risk stratification., Recent Findings: Expressed as the product of plaque area and a peak calcium density weighting factor, the Agatston method is the gold-standard for measuring CAC on noncontrast cardiac computed tomography. Over the last decade, observational data have suggested that calcium density is inversely associated with CVD events and confers additional prognostic information independent of traditional risk factors and Agatston CAC scores. Specific density measures have been assessed including peak calcium density, mean CAC density, and CAC area-density discordance. Beyond calcium density, the number of affected arteries and regional distribution of CAC which may be correlated with CAC density have also improved the predictive utility of the Agatston score., Summary: Calcium density is inversely associated with CVD risk after considering plaque area and/or volume. Calcium markers including density, vessel involvement, and regional distribution confer additional prognostic information for the prediction of incident CVD among those with prevalent subclinical atherosclerosis. A future area of study includes calcium radiomics ('calcium-omics') and whether the artificial intelligence-derived automated measurement of calcium markers beyond the Agatston score may be of value in CVD risk stratification among individuals with early to advanced subclinical atherosclerosis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: We aimed to investigate the interplay between low-density lipoprotein-cholesterol (LDL-C) and coronary plaque in asymptomatic cohorts undergoing coronary tomography angiography (CCTA) assessment in the United States., Methods: A cross-sectional analysis of baseline data from 1808 statin-naïve participants in the Miami Heart Study was conducted. We assessed CCTA-detected atherosclerosis (any plaque, noncalcified plaque, maximal stenosis ≥50%, high-risk plaque) across LDL-C levels, coronary artery calcium (CAC) scores (0, 1-99, ≥100), and 10-year cardiovascular risk categories., Results: Atherosclerosis presence varied across LDL-C levels: 40% of those with LDL-C ≥190 mg/dL had no coronary plaque, while 33% with LDL-C <70 mg/dL had plaque (22.4% with noncalcified plaque). Among those with CAC 0, plaque prevalence ranged from 13.2% (LDL-C <70 mg/dL) to 28.2% (LDL-C ≥190 mg/dL), noncalcified plaque from 13.2% to 25.6%, stenosis ≥50% from 0 to 2.6%, and high-risk plaque from 0 to 5.1%. Conversely, with CAC ≥100, all had coronary plaque, with noncalcified plaque prevalence ranging from 25.0% (LDL-C <70 mg/dL) to 83.3% (LDL-C ≥190 mg/dL), stenosis ≥50% from 25.0% to 50.0%, and high-risk plaque from 0 to 66.7%. Among low-risk participants, 76.7% had CAC 0, yet 31.5% had any plaque and 18.3% had noncalcified plaque. Positive trends between LDL-C and any plaque (17.9%-45.2%) or noncalcified plaque (12.8%-23.8%) were observed in the low-risk group, but no clear trends were seen in higher-risk groups., Conclusions: Heterogeneity exists in subclinical atherosclerosis across LDL-C, CAC, and estimated cardiovascular risk levels. The value of CCTA in risk-stratifying asymptomatic adults should be further explored., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Nasir is on the advisory board of Amgen, Novartis, Novo Nordisk, his research is partly supported by the Jerold B. Katz Academy of Translational Research and is a member of the Steering Committee of the PAK-SEHAT study which is partly funded by an unrestricted research grant from Getz Pharma. Dr. Cainzos-Achirica is on the Steering Committee of the PAK-SEHAT Study, partially funded by an unrestricted research grant from Getz Pharma. Dr. Shapiro has served on Scientific Advisory Boards with Amgen, Ionis, Novartis, Precision BioScience and as a consultant for Ionis, Novartis, Regeneron, EmendoBio, Aidoc. Dr. Cury is a consultant to GE Healthcare, Covera Health and Cleerly., (Copyright © 2024. Published by Elsevier B.V.)

Background and Aims: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: AVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1000 person-years) and multivariable adjusted Cox proportional hazards ratios (HR)., Results: Overall, 6812 participants had AVC quantified with a mean age of 62.1 years old, 52.9 % were women, and the median 10-year estimated atherosclerotic cardiovascular disease (ASCVD) risk was 13.5 %. Participants with AVC >0 were older and less likely to be women compared to those with AVC=0. Over a median 16-year follow-up, there were 535 cases of dementia and 376 cases of stroke. The absolute risk of newly diagnosed dementia increased in a stepwise pattern with higher AVC scores, and stroke increased in a logarithmic pattern. In multivariable analyses, AVC was significantly associated with newly diagnosed dementia as a log-transformed continuous variable (HR 1.09; 95 % CI 1.04-1.14) and persons with AVC ≥300 had nearly a two-fold higher risk (HR 1.77; 95 % CI 1.14-2.76) compared to those with AVC=0. AVC was associated with an increased risk of stroke after adjustment for age, sex, and race/ethnicity, but not after adjustment for ASCVD risk factors., Conclusions: After multivariable adjustment, AVC >0 was significantly associated with an increased risk of newly diagnosed dementia, but not incident stroke. This suggests that AVC may be an important risk factor for the long-term risk of dementia beyond traditional ASCVD risk factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Both diabetes and smoking significantly increase the risk of cardiovascular disease (CVD). Understanding whether a diagnosis of diabetes can be leveraged to promote smoking cessation is a gap in the literature., Methods: We used data from the US National Health Interview Survey, 2006 to 2018, to investigate the relationship between self-report of diagnosis of diabetes and subsequent smoking abstinence among 142,884 respondents who reported regular smoking at baseline. Effect sizes were presented as hazard ratios (HRs) derived from multivariable Cox regression models adjusted for potential confounders using diabetes as a time-dependent covariate. Subgroup-specific estimates were obtained using interaction terms between diabetes and variables of interest., Results: A self-reported diagnosis of diabetes was associated with smoking abstinence (HR: 1.21; 95% CI: 1.16 to 1.27). The strength of the association varied based on race (P for interaction: 0.004), where it was strongest in African Americans (HR: 1.44; 95% CI: 1.29 to 1.60); income (P for interaction <0.001), where it was strongest in those with a yearly income less than $35,000 (HR: 1.45; 95% CI: 1.36 to 1.53); and educational attainment (P for interaction <0.001), where it was strongest in those who did not attend college (HR: 1.48; 95% CI: 1.40 to 1.57)., Conclusion: Among adults who smoke, a diagnosis of diabetes is significantly associated with subsequent smoking abstinence. The association is strongest in socially disadvantaged demographics, including African Americans, low-income individuals, and those who did not attend college., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Understanding the association between initial experimentation with a tobacco product and subsequent patterns of tobacco use among youth is important to informing prevention activities for youth in the US. We conducted an online survey from August to October 2017 among youth aged 13-18 years. The current analysis focused on respondents reporting initial experimentation with any tobacco product (n = 2,022). Using multinomial logistic regression, we examined the association between first tobacco product tried (cigarettes; cigars including cigarillos, little cigars, and bidis; electronic nicotine delivery systems (ENDS); smokeless and chewing tobacco; or hookah) with subsequent patterns of tobacco use while adjusting for covariates. Of the youth who experimented, 56.8% were non-current tobacco users. Of current tobacco users (n = 934), 13% were exclusive ENDS users, 5.3% exclusive combustible mono-users, 13.4% ENDS plus combustible poly-users, 3.3% combustible product only poly-users, and 8.2% other tobacco poly-users. The most common type of first tobacco product tried was ENDS (44.7%), followed by cigarettes (35.0%) and cigars (8.6%). Those who experimented with combustible tobacco products were less likely to be exclusive ENDS users [Relative Risk Ratio (RRR) = 0.46; 95% CI = 0.28, 0.73 for cigarettes; RRR = 0.32; 95% CI = 0.13, 0.81 for cigars; and RRR = 0.33; 95% CI = 0.14, 0.79 for hookah] when compared to non-current tobacco users (reference group). Tobacco product choices for initial experimentation appear to play a role in subsequent tobacco use patterns among youth. Understanding the reasons behind initial product choice may inform our understanding regarding the reasons for subsequent current tobacco product use, thus informing youth prevention efforts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 El-Shahawy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Prior consensus meetings have addressed the relationship between phosphodiesterase type 5 (PDE5) inhibition and cardiac health. Given significant accumulation of new data in the past decade, a fourth consensus conference on this topic was convened in Pasadena, California, on March 10 and 11, 2023., Objectives: Our meeting aimed to update existing knowledge, assess current guidelines, and make recommendations for future research and practice in this area., Methods: An expert panel reviewed existing research and clinical practice guidelines., Results: Key findings and clinical recommendations are the following: First, erectile dysfunction (ED) is a risk marker and enhancer for cardiovascular (CV) disease. For men with ED and intermediate levels of CV risk, coronary artery calcium (CAC) computed tomography should be considered in addition to previous management algorithms. Second, sexual activity is generally safe for men with ED, although stress testing should still be considered for men with reduced exercise tolerance or ischemia. Third, the safety of PDE5 inhibitor use with concomitant medications was reviewed in depth, particularly concomitant use with nitrates or alpha-blockers. With rare exceptions, PDE5 inhibitors can be safely used in men being treated for hypertension, lower urinary tract symptoms and other common male disorders. Fourth, for men unresponsive to oral therapy or with absolute contraindications for PDE5 inhibitor administration, multiple treatment options can be selected. These were reviewed in depth with clinical recommendations. Fifth, evidence from retrospective studies points strongly toward cardioprotective effects of chronic PDE5-inhibitor use in men. Decreased rates of adverse cardiac outcomes in men taking PDE-5 inhibitors has been consistently reported from multiple studies. Sixth, recommendations were made regarding over-the-counter access and potential risks of dietary supplement adulteration. Seventh, although limited data exist in women, PDE5 inhibitors are generally safe and are being tested for use in multiple new indications., Conclusion: Studies support the overall cardiovascular safety of the PDE5 inhibitors. New indications and applications were reviewed in depth., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The absence of coronary artery calcium (CAC = 0) is associated with low risk of stroke events; however, predictors of incident stroke among those with CAC = 0 are not known., Methods: Individual participant-level data were pooled from three prospective cohorts (Multi-Ethnic Study of Atherosclerosis, Jackson Heart Study, and Framingham Heart Study). Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors and incident adjudicated stroke among individuals with CAC = 0 who were free of clinical atherosclerotic cardiovascular disease at baseline., Results: Among 6180 participants (mean age 53 [SD 11] years, 62% women, and 44% White, 36% Black, and 20% other individuals), over a median (IQR) follow up of 15 (12-16) years, there were 122 strokes (95 ischemic, 27 hemorrhagic) with an overall unadjusted event rate of 2.0 per 1000 person-years. After multivariable adjustment, risk factors associated with overall stroke included (hazard ratio [95% CI]) systolic blood pressure (SBP): 1.19 (1.05-1.36) per 10-mmHg increase and carotid intima-media thickness (CIMT): 1.21 (1.04-1.42) per 0.1-mm increment. Current cigarette smoking: 2.68 (1.11-6.50), SBP: 1.23 (1.06-1.42) per 10-mmHg increase, and CIMT: 1.25 (1.04-1.49) per 0.1-mm increment were associated with ischemic stroke, whereas C-reactive protein was associated with hemorrhagic stroke risk (0.49, 0.25-0.93)., Conclusion: In a large cohort of individuals with CAC = 0, the rate for incident stroke was low (2.0 per 1000-person years) and was associated with modifiable risk factors., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Vijay Nambi: site PI study sponsored by Merck and Amgen. Christie M Ballantyne: received grant/research support (to his institution) from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostic; and has been a consultant for 89bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Matinas BioPharma Inc., Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostic. Salim S Virani: received research funding from Department of Veterans Affairs, NIH, World Heart Federation, and Tahir and Jooma Family; and receives honorarium from the American College of Cardiology. The remaining authors have no conflicts of interest.

The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative symposium dedicated to optimizing sexual function and preserving cardiovascular health. The Fourth Princeton Consensus Conference was convened on March 10-11, 2023, at the Huntington Medical Research Institutes in Pasadena, California. Princeton panels I to III addressed the clinical management of men with erectile dysfunction (ED) who also had cardiovascular disease. Thirteen years since Princeton III, Princeton IV builds on previous foundations in several key areas. Mounting evidence supports the need for providers to treat men with ED as being at risk for cardiac events until proven otherwise. Algorithms for the diagnosis and treatment of ED are updated with new recommendations for coronary artery calcium scoring for advanced cardiovascular risk stratification. Optimization of oral phosphodiesterase type 5 inhibitors in the treatment of men with ED and cardiovascular disease is thoroughly explored, including recent evidence of potential cardioprotective effects of these drugs., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Compared to normal high-density lipoprotein (HDL) cholesterol values, very high HDL cholesterol is associated with a higher incidence of mortality and atherosclerotic cardiovascular disease (ASCVD). As such, clinical risk stratification among persons with very high HDL cholesterol is challenging., Objectives: Among persons with very high HDL cholesterol, the purpose was to determine the prevalence of coronary artery calcium (CAC) and compare the association between traditional risk factors vs CAC for all-cause mortality and ASCVD., Methods: The primary analysis was completed among 446 participants from the Cedars-Sinai Medical Center of the CAC Consortium with very high HDL cholesterol (≥77 mg/dL in men, ≥97 mg/dL in women). Cox proportional hazards regression assessed the association of CAC and traditional risk factors with all-cause mortality during a median follow-up of 10.7 years. Replication and validation analyses were performed for all-cause mortality among 119 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with very high HDL cholesterol, who also had information on incident ASCVD., Results: The mean age was 57.9 years old, 49% were women, and the median HDL cholesterol was 98 mg/dL. One-half of participants (50%) had prevalent CAC, in whom the median CAC score was 118. Prevalent CAC conferred a 3.6-fold higher risk of all-cause mortality (HR: 3.64; 95% CI: 1.21-11.01), which appeared to be a more robust predictor than individual traditional risk factors beyond age. In the validation sample, prevalent CAC but not individual traditional risk factors were associated with all-cause mortality (HR: 2.39; 95% CI: 1.07-5.34) and a 4.0-fold higher risk of ASCVD (HR: 4.06; 95% CI: 1.11-14.84)., Conclusions: Measurement of CAC may facilitate clinical risk assessment among individuals with very high HDL cholesterol., Competing Interests: This research was supported by R01HL071739 and R01HL146666, and MESA was supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the 10.13039/100000050National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the 10.13039/100006108National Center for Advancing Translational Sciences (NCATS). Dr Blaha has received grants from the 10.13039/100000002National Institutes of Health, 10.13039/100000038U.S. Food and Drug Administration, 10.13039/100000968American Heart Association (AHA) grant number 24POST1195187, and 10.13039/100000045Aetna Foundation; grants and personal fees from Amgen, Bayer, and Novo Nordisk; and personal fees from Novartis, Roche, Merck, Boehringer Ingelheim, Vectura, Agepha, and AstraZeneca outside the submitted work. Dr Dzaye has received support from National Institutes of Health grant T32 HL007227. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have surged in popularity in recent years, with discussions about their on-label and off-label use spilling into the public forum. No study has analyzed online discussions about GLP-1RAs., Objectives: The purpose of this study was to analyze perceptions of GLP-1RAs on social media., Methods: We analyzed GLP-1RA-related posts on Reddit between May 28, 2013, and June 1, 2023. All posts were identified that included generic or brand names of GLP-1RAs. Post volume on Reddit was compared to search interest on Google over time. An artificial intelligence (AI) pipeline consisting of a semi-supervised natural language processing model (Bidirectional Encoder Representations from Transformers [BERT]), a dimensionality reduction technique, and a clustering algorithm was used to cluster posts into related topics. Discussion sentiment was classified using a pretrained BERT model and assessed qualitatively., Results: 14,390 GLP-1RA-related Reddit posts by 8,412 authors were identified. Ninety-four percent of posts were created after 2021, consistent with search interest trend on Google. We used the AI model to categorize posts into 30 topics which were hierarchically grouped by the model based on shared content. Posts were identified among communities for individuals with diabetes and obesity, as well as for diseases without a Food and Drug Administration-approved indication. Most posts had a negative sentiment using the pretrained model, acknowledging the pretrained model is at risk for misclassifying posts., Conclusions: AI can generate insights on perceptions of GLP-1RAs on social media. Common themes included success stories of improving diabetes and obesity management, struggles with insurance coverage, and questions regarding diet, side effects, and medication administration., Competing Interests: Under a license agreement between Corrie Health and Johns Hopkins University, the university owns equity in Corrie Health. The university, Drs Marvel and Martin are entitled to royalty distributions related to Corrie Health. In addition, Drs Marvel and Martin are cofounders of and hold equity in Corrie Health. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies. Drs Marvel and Martin have also received research and material support from 10.13039/100017567Apple. Furthermore, Dr Martin is on the Advisory Board for Care Access and reports personal consulting fees from Amgen, BMS, AstraZeneca, Chroma, Kaneka, NewAmsterdam, Novartis, Novo Nordisk, Premier, Sanofi, and 89bio; and also reports research support from the 10.13039/100000968American Heart Association (20SFRN35380046, 20SFRN35490003, #878924, #882415, #946222), the 10.13039/100006093Patient-Centered Outcomes Research Institute (ME-2019C1-15 328, IHS-2021C3-24147), the 10.13039/100000002National Institutes of Health (NIH) (P01 HL108800 and R01AG071032), the 10.13039/100015926David and June Trone Family Foundation, the Pollin Digital Innovation Fund, Sandra and Larry Small, Google, and Merck. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)