The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Review Early identification of coronary atherosclerotic pathogenic mechanisms is useful for predicting the risk of coronary heart disease (CHD) and future cardiac events. Epigenome changes may clarify a significant fraction of this "missing hereditability", thus offering novel potential biomarkers for prevention and care of CHD. The rapidly growing disciplines of systems biology and network science are now poised to meet the fields of precision medicine and personalized therapy. Network medicine integrates standard clinical recording and non-invasive, advanced cardiac imaging tools with epigenetics into deep learning for in-depth CHD molecular phenotyping. This approach could potentially explore developing novel drugs from natural compounds (i.e. polyphenols, folic acid) and repurposing current drugs, such as statins and metformin. Several clinical trials have exploited epigenetic tags and epigenetic sensitive drugs both in primary and secondary prevention. Due to their stability in plasma and easiness of detection, many ongoing clinical trials are focused on the evaluation of circulating miRNAs (e.g. miR-8059 and miR-320a) in blood, in association with imaging parameters such as coronary calcifications and stenosis degree detected by coronary computed tomography angiography (CCTA), or functional parameters provided by FFR/CT and PET/CT. Although epigenetic modifications have also been prioritized through network based approaches, the whole set of molecular interactions (interactome) in CHD is still under investigation for primary prevention strategies. events 10, 11). In the era of next generation sequencing, the development of a plethora of high-throughput platforms has provided significant impact concerning the knowledge of CHD molecular characterization generating big "omics" data sets 12-14). Furthermore, several non-invasive imaging techniques have been developed over the last few years to detect CHD with the aim to guide optimal patient management, such as coronary computed tomography angiography (CCTA), cardiac magnetic resonance (CMR), and nuclear medicine technique positron emission tomography (PET) 15). These advances have raised challenges Copyright©2020 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

PCSK9 inhibitors (PCSK9i) are monoclonal antibodies that have been shown to be effective in reducing both LDL cholesterol (LDL-C) values and major cardiovascular events in patients at high cardiovascular risk. Adherence to PCSK9i is critical for the success of the treatment. The aim of the present study is to evaluate patients’ adherence to PCSK9i during the COVID-19 pandemic. Patients referred to the Cardiac Diagnostic Unit of the University of Campania “Luigi Vanvitelli” Naples, taking PCSK9i, and who missed the cardiological follow-up visit during the first national COVID-19 lockdown (9 March–17 May 2020), were included. Each patient underwent medical teleconsultation to collect current clinical conditions, adherence to drug treatments, and lipid profile laboratory tests. Among 151 eligible patients, 20 were excluded for missing or untraceable telephone numbers and one for refusing to join the interview. The selected study population consisted of 130 patients (64 ± 9 years, 68% males), of whom 11 (8.5%) reported a temporary interruption of the PCSK-9 therapy for a mean period of 65 ± 1.5 days. The non-adherent patients showed a marked increase in LDL-C than in the pre-pandemic period (90.8 ± 6.0 vs. 54.4 ± 7.7 mg/dL, p < 0.0001), and 82% of patients moved out of the LDL-C therapeutic range. The non-adherent group was more likely to have a very high cardiovascular risk compared to the adherent group (81.8 vs. 33.6%, p < 0.001). Causes of interruption included drug prescription failure (63.6%) due to temporary interruption of the non-urgent outpatient visits and failure in drug withdrawal (36.4%) due to patients’ fear of becoming infected during the pandemic. The COVID-19 lockdown caused a remarkable lack of adherence to PCSK9i therapy, risking negative implications for the health status of patients at high cardiovascular risk. Facilitating patients’ access to PCSK9i and enhancing telemedicine seem to be effective strategies to ensure the continuity of care and appropriate management of these patients.

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