Coronary artery calcium in 2023: Guidelines for LDL-C goals, non-statin therapies, and aspirin use.

Personalizing risk assessment and treatment decisions for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) rely on pooled cohort equations and increasingly coronary artery calcium (CAC) score. A growing body of evidence supports that elevated CAC scores correspond to progressively elevated ASCVD risk, and that scores of ≥100, ≥300, and ≥1000 denote risk that is equivalent to certain secondary prevention populations. This has led consensus guidelines to incorporate CAC score thresholds for guiding escalation of preventive therapy for lowering low-density lipoprotein cholesterol goals, initiation of non-statin lipid lowering medications, and use of low-dose daily aspirin. As data on CAC continues to grow, more decision pathways will incorporate CAC score cutoffs to guide management of blood pressure and cardiometabolic medications. CAC score is also being used to enrich clinical trial study populations for elevated ASCVD risk, and to screen for subclinical coronary atherosclerosis in patients who received chest imaging for other diagnostic purposes.

Cardiometabolic medicine: a review of the current proposed approaches to revamped training in the United States.

Cardiovascular disease (CVD) remains the leading cause of mortality in the United States, and the population of patients with cardiometabolic conditions, including obesity, metabolic syndrome and diabetes mellitus, continues to grow. There is a need for physicians with specific training in cardiometabolic medicine to provide a 'medical home' for patients with cardiometabolic disease, rather than the fractured care that currently exists in the United States. Cardiometabolic specialists will head multidisciplinary clinics, develop practice guidelines, and lead through research. Proposals for US training in cardiometabolic medicine include: maintain the current training model, a dedicated 2-3 year fellowship following internal medicine residency, a 1-year fellowship following either internal medicine residency or fellowship in cardiology or endocrinology, and certification available to any interested clinician. This review discusses the pros and cons of these approaches. The authors believe that a dedicated cardiometabolic training fellowship has significant advantages over the other options.

Antigen-driven clonal selection shapes the persistence of HIV-1-infected CD4+ T cells in vivo.

Clonal expansion of infected CD4+ T cells is a major mechanism of HIV-1 persistence and a barrier to achieving a cure. Potential causes are homeostatic proliferation, effects of HIV-1 integration, and interaction with antigens. Here, we show that it is possible to link antigen responsiveness, the full proviral sequence, the integration site, and the T cell receptor ß-chain (TCRß) sequence to examine the role of recurrent antigenic exposure in maintaining the HIV-1 reservoir. We isolated CMV- and Gag-responding CD4+ T cells from 10 treated individuals. Proviral populations in CMV-responding cells were dominated by large clones, including clones harboring replication-competent proviruses. TCRß repertoires showed high clonality driven by converging adaptive responses. Although some proviruses were in genes linked to HIV-1 persistence (BACH2, STAT5B, MKL1), the proliferation of infected cells under antigenic stimulation occurred regardless of the site of integration. Paired TCRß and integration site analysis showed that infection could occur early or late in the course of a clone's response to antigen and could generate infected cell populations too large to be explained solely by homeostatic proliferation. Together, these findings implicate antigen-driven clonal selection as a major factor in HIV-1 persistence, a finding that will be a difficult challenge to eradication efforts.