When Does Primary Prevention Encroach on Secondary Prevention?

PURPOSE OF REVIEW: The risk of incident atherosclerotic cardiovascular disease (ASCVD) in primary prevention is typically lower than in secondary prevention. However, there is a spectrum of risk among individuals undergoing primary prevention with the risk in some individuals approaching those of secondary prevention. We review the clinical conditions wherein the risk in primary prevention is similar to that observed in secondary prevention. RECENT FINDINGS: Among individuals without established ASCVD, coronary artery calcium (CAC) scores ≥ 300 AU are associated with ASCVD event rates similar to secondary prevention populations. CAC score ≥ 1,000 AU are associated with an ASCVD risk seen in very high-risk secondary prevention populations. Interpretation of these observations must however consider differences in the risk reduction strategies. Current guidelines dichotomize ASCVD prevention into primary and secondary prevention, but certain primary prevention patients have an ASCVD risk equivalent to that of secondary prevention populations. Identifying higher risk primary prevention populations will allow for better risk mitigation strategies.

Circulating isomiRs May Be Superior Biomarkers Compared to Their Corresponding miRNAs: A Pilot Biomarker Study of Using isomiR-Ome to Detect Coronary Calcium-Based Cardiovascular Risk in Patients with NAFLD.

Circulating miRNAs are increasingly being considered as biomarkers in various medical contexts, but the value of analyzing isomiRs (isoforms of canonical miRNA sequences) has not frequently been assessed. Here we hypothesize that an in-depth analysis of the full circulating miRNA landscape could identify specific isomiRs that are stronger biomarkers, compared to their corresponding miRNA, for identifying increased CV risk in patients with non-alcoholic fatty liver disease (NAFLD)-a clinical unmet need. Plasma miRNAs were sequenced with next-generation sequencing (NGS). Liver fat content was measured with magnetic-resonance spectrometry (MRS); CV risk was determined, beyond using traditional biomarkers, by a CT-based measurement of coronary artery calcium (CAC) score and the calculation of a CAC score-based CV-risk percentile (CAC-CV%). This pilot study included n = 13 patients, age > 45 years, with an MRS-measured liver fat content of ≥5% (wt/wt), and free of overt CVD. NGS identified 1103 miRNAs and 404,022 different isomiRs, of which 280 (25%) and 1418 (0.35%), respectively, passed an abundance threshold. Eighteen (sixteen/two) circulating miRNAs correlated positively/negatively, respectively, with CAC-CV%, nine of which also significantly discriminated between high/low CV risk through ROC-AUC analysis. IsomiR-ome analyses uncovered 67 isomiRs highly correlated (R ≥ 0.55) with CAC-CV%. Specific isomiRs of miRNAs 101-3p, 144-3p, 421, and 484 exhibited stronger associations with CAC-CV% compared to their corresponding miRNA. Additionally, while miRNAs 140-3p, 223-3p, 30e-5p, and 342-3p did not correlate with CAC-CV%, specific isomiRs with altered seed sequences exhibited a strong correlation with coronary atherosclerosis burden. Their predicted isomiRs-specific targets were uniquely enriched (compared to their canonical miRNA sequence) in CV Disease (CVD)-related pathways. Two of the isomiRs exhibited discriminative ROC-AUC, and another two showed a correlation with reverse cholesterol transport from cholesterol-loaded macrophages to ApoB-depleted plasma. In summary, we propose a pipeline for exploring circulating isomiR-ome as an approach to uncover novel and strong CVD biomarkers.

Transient ischaemic dilation ratio thresholds in patients with zero coronary calcium score undergoing exercise or dipyridamole stress SPECT myocardial perfusion imaging using a cadmium-zinc-telluride camera.

Aims: Transient ischaemic dilation (TID) is a marker of underlying extensive coronary artery disease (CAD) during myocardial perfusion imaging (MPI). The cut-off for a normal TID ratio (TIDr) value is often derived from a cohort of individuals with no apparent CAD. Varying criteria have been used to define the absence of CAD. We aim to derive TIDr cut-offs using patients with normal MPI and coronary artery calcium (CAC) score of zero, and compare the TIDr obtained from different software packages. Methods and results: We studied 232 patients with zero CAC and normal MPI undergoing exercise or dipyridamole stress using either a 1- or 2-day protocol. All patients were scanned in the supine position with a cadmium-zinc-telluride camera. TIDr was automatically generated using quantitative perfusion SPECT (QPS) software initially, and subsequently using Myometrix for comparison. The TIDr cut-offs calculated using the mean + 2 standard deviation were 1.29 and 1.24 for the 1- and 2-day protocol groups, respectively. In patients undergoing a 2-day protocol, dipyridamole stress resulted in significantly higher mean TIDr when compared to exercise stress (1.07 ± 0.13 vs. 1.01 ± 0.12, P = 0.035). Myometrix-derived TIDr were also significantly lower compared to QPS-derived values for most protocols except for 2-day exercise stress. Conclusion: This study is the first to derive TIDr threshold values using a normal population defined by zero CAC and normal MPI. TIDr was found to vary depending on stress modality, protocol as well as the software used.

Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil

Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Valor predictivo de la tomografía multicorte para evaluar lesiones obstructivas coronarias, en el preoperatorio de cirugía cardiaca no coronaria / Predictive value of multi-sliced computed tomography to evaluate obstructive coronary vessel, in the preoperative assessment of non-coronary cardiac surgery

Introducción: En la actualidad la enfermedad coronaria obstructiva (obstrucción mayor de 50%) puede ser fácilmente evaluada por medio de la tomografía coronaria multicorte. Sin embargo, aún no se define si ésta puede reemplazar a la angiografía coronaria invasiva, en pacientes que van a cirugía cardiaca no coronaria. Objetivo: Conocer si la tomografía coronaria multicorte puede sustituir a la angiografía coronaria invasiva en la detección de enfermedad coronaria en pacientes que van a ser operados de cirugía cardiaca no coronaria; comparando entre si la sensibilidad y especificidad de ambos métodos en la detección de enfermedad coronaria. Método: Se incluyeron consecutivamente 64 pacientes con edades de 55.17 ± 12.73 años, en Clase I de las guías del Colegio Americano de Cardiología/Asociación Americana de Corazón para realizar angiografía coronaria en el preoperatorio de cirugía cardiaca no coronaria. Se excluyeron enfermos con angina de pecho, alergia al medio de contraste, creatinina sérica por arriba de 2.0 mg/dL, que tuvieran previamente cirugía cardiaca o angioplastia coronaria y arritmias supra-ventriculares. Se analizó la anatomía coronaria y se cuantificó la cantidad de calcio coronario. Resultados: La prevalencia de obstrucción coronaria mayor de 50% fue 12.5%. La tomografía coronaria multicorte mostró sensibilidad de 87.5%, especificidad de 92.8%, valor predictivo negativo de 98.1% y área bajo la curva de 0.90, para predecir obstrucción coronaria. Ningún paciente con valvulopatía reumática tuvo obstrucción coronaria mayor de 50% o score de calcio > 400 U A (RR = 0.80, IC 95% 0.69-0.94). La estenosis valvular aórtica degenerativa tuvo mayor probabilidad de obstrucción coronaria mayor de 50% (RR = 9.0: IC 95% 1.64-49.8). Con análisis multivariado usando regresión logística, el score de calcio mayor de 400 UA (Coef ß 0.342, t = 4.297, p = 0.000) y sexo masculino (Coef ß 0.174, t = 2.214, p = 0.031), fueron las variables predictoras de más peso. Este estudio muestra poblaciones diferentes en el grupo de pacientes que van a cirugía cardiaca no coronaria. Conclusiones: El género masculino, el calcio coronario mayor de 400 UA y el tipo de enfermedad cardiaca previa a la cirugía cardiaca no coronaria pueden ser variables útiles para realizar la selección de pacientes que pueden evaluarse con tomografía coronaria multicorte o con angiografía coronaria invasiva. La angiografía coronaria invasiva puede indicarse necesariamente en algunos pacientes que van a cirugía cardiaca no coronaria, pero no es absolutamente necesaria en todos los enfermos como hasta hoy se recomienda en las guías del Colegio Americano de Cardiología y la Asociación Americana de Corazón.

Introduction: Significant Coronary Artery Disease (CAD>50%) it can easily detected with Multislice Computed Tomography (MSCT), nevertheless if MSCT may replace Invasive Coronary Angiography (ICA) in the preoperative assessment of the patient undergoing to non-coronary cardiac surgery is not well defined. The objective of this study was to know if the MSCT can replace ICA in the preoperative valuation of patients who go to cardiac surgery Method: 64 consecutive patients in Class I recommendation of American College of Cardiology / American Heart Association (ACC/AHA) guidelines for preoperative ICA were evaluated. Patients with angina, contrast medium allergy, serum creatinine up to 2.0 mg/dL, previous coronary cardiac surgery or coronary angioplasty and supraventricular arrhythmias were excluded. Both, Coronary artery calcium (CAC) and coronary angiography were evaluated. Results: The prevalence of significant (>50%) CAD was 12.5%. The Sensitivity of MSCT to detect significant CAD was 87.5%, its Specificity of 92.8%, Predictive Negative Value was 98.1% and Area Under the Curve (ROC analysis) = 0.90. Anyone with Rheumatic Valvular Disease had significant CAD or CAC>400 UA (RR = 0.80, IC95% 0.69-0.94). Degenerative Aortic Valve Stenosis had a major probability of significant CAD (RR of 9.0; IC 95% 1.64-49.80). Logistic Regression Analysis showed than CAC>400 UA (Coef ß 0,351, t = 4.402 p = 0.000) and male gender (Coef ß 0,179, t = 2.445, p = 0.017), were the best predicting variables of CAD. This study shows different populations in patients undergoing to non-coronary cardiac surgery. Conclusions: Gender, CAC> 400 UA and type of cardiac disease previously surgery may be useful for triage to MSCT or ICA in the preoperative assessment. This study shows that ICA may be necessarily indicated in some patients in assessment of non-coronary cardiac surgery but not absolutely indicated in all patients that Guidelines of ACC/AHA have recommended.