Prevention of Coronary Heart Disease: A Translational Clinical Challenge

Introduction: Atherosclerotic cardiovascular disease is a dysmetabolic medical condition resulting in the #1 cause of morbidity and mortality in the United States. Coronary Artery Calcium (CAC) CT non-invasively identifies atherosclerosis in asymptomatic individuals. This translational study tested the hypothesis that clinically overtcardiovascular disease can be prevented in asymptomatic individuals in a medical clinic. Methods: Two hundred and six asymptomatic adults requested a CAC scan to identify subclinical heart disease. Individuals with a positive CAC score > 1 (n = 125) were prescribed targeted medical therapy to reverse their atherosclerosis. The goal was to achieve an LDL Cholesterol (LDL-C) ≤ 60 mg/dl. One hundred and ten individuals reached this goal (67 male, 43 female) receiving 10 mg/d of rosuvastatin and 10 mg/d of ezetimibe plus a low cholesterol diet. Other fifteen individuals with positive CAC scores did not achieve this LDL-C goal. Results: In the group following medical therapy and achieving an LDL-C ≤ 60 mg/dl, no cardiovascular events were observed during a maximum observation period of 5 years (mean observation time = 3.6 years). Based on previously published CVD outcome data in individuals with similar CAC scores, 12.6 cardiovascular events were expected. Two of fifteen individuals with positive CAC scores not following medical therapy had a cardiovascular event. None of the 81 individuals with a zero score had a cardiovascular event during follow-up. No adverse effects of therapy occurred. Conclusion: In a medical clinic, adult population with positive CAC scores and an LDL-C ≤ 60 mg/dl, targeted medical therapy prevented overt cardiovascular disease. These results should encourage other physicians to aggressively treat atherosclerotic cardiovascular disease in their clinic populations.

Preventing Heart Disease via Coronary Artery Calcium Scoring to Make a Definitive Diagnosis of Atherosclerosis

Purpose: Cardiovascular disease is the number one cause of death in the Western world. The purpose of this manuscript is to compare the benefits and deficiencies of coronary artery calcium scanning versus computer generated risk equations in identifying atherosclerotic cardiovascular disease. These two approaches provide significantly different cardiovascular risk assessments and often lead to therapeutic differences in recommendations from the physician to the patient. Methods: Pertinent medical literature is reviewed concerning both risk assessment approaches (i.e., coronary artery scanning and computer generated risk equations). The strengths and weaknesses of both approaches are discussed, and recommendations are provided based upon available data. Results: Cardiovascular risk equations are simple and readily obtained at no charge by physicians. However, their drawbacks are several, including non-applicability to specific populations, disagreements among different cardiovascular society risk equations, wide ranges of risk outputs (e.g., intermediate 10-year risk is between 5% and 20%), inability to definitively identify coronary artery plaques, and lack of definitive anatomical coronary disease. Alternatively, coronary artery calcium scanning costs approximately $100/scan (if not covered by insurance), requires time and effort by the patient, and exposes the patient to a minimal amount of radiation. However, coronary calcium scanning identifies specific atherosclerotic coronary disease and provides additional information about the anatomical location (i.e., coronary artery) of the atherosclerotic plaque. Conclusion: Based on the published literature, coronary artery calcium scanning is the preferred approach for identifying atherosclerotic cardiovascular disease. Although there are minor drawbacks, overall it provides superior clinical information compared with computer generated risk equations.

A novel method for identifying SARS-CoV-2 infection mutants via an epitope-specific CD8^(+)T cell test

Since the outbreak of the coronavirus disease 2019(COVID-19)epidemic in 2019,the public health system has faced enormous challenges.Tracking the individuals who test positive for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a key step for interrupting chains of transmission of SARS-CoV-2 and reducing COVID-19-associated mortality.With the increasing of asymptomatic infections,it is difficult to track asymptomatic infections through epidemiological surveys and virus whole-genome sequencing.However,due to the cross-reactivity of neutralizing antibodies produced by multiple virus subtypes,neutralizing antibody detection cannot be used to determine whether an individual has a history of infection with a specific subtype of SARS-CoV-2.We recruited 4 human leukocyte antigen A2(HLA-A2)infections,15 individuals who received three doses of inactivated vaccines,and 30 breakthrough infections after vaccination and discussed a case-tracking approach to detect epitope-specific CD8^(+)T cells in the peripheral blood of close contacts,including accurate HLA typing based on ribonucleic acid(RNA)-sequencing and flow cytometry data and the comparison and characterization of SARS-CoV-2 HLA-A2 and HLA-A24 epitope-specific CD8^(+)T cells.From individuals who received three doses of inactivated vaccine,we observed that the CD8^(+)T cell specificity for ancestral epitopes was significantly higher than for mutated epitopes,and the fold change of CD8^(+)T cells corresponding to mutated epitopes relative to ancestral epitopes was less than 1.The enzyme-linked immunospot(ELISpot)results further validate this result.This study forms a“method for understanding the infection history of SARS-CoV-2 subtypes based on the proportion of epitope-specific CD8^(+)T cells in the peripheral blood of subjects”,covering up to 46%of the population,including HLA-A2+and HLA-A24+donors,providing a novel method for SARS-CoV-2 infected case tracing.