Concomitant coronary artery disease development in identical twins: a case report and a systematic literature review
Authors: Papazoglou A , Gemousakakis E , Kamzolas O , Moysidis D , Milkas A 
Published: November 2023

Abstract

Case summary: Two 47-year-old monozygotic male twins presented to a tertiary hospital with chest pain (having a 3-month difference in their presentation). They were both smokers without any other standard modifiable risk factor or positive family history. Coronary angiograms of both twins demonstrated concordant coronary anatomy and obstructive CAD in two major epicardial coronary vessels with nearly identical lesions. Lipoprotein(a) [lp(a)] levels were substantially elevated in both twins (170 and 120 mg/dl respectively). Aiming to explain the almost identical CAD observed, next-generation whole-exome sequencing analyses were performed; however, no disease-causing CAD- or lp(a)-related mutation could be identified.

Background
The occurrence of CAD is strongly affected by genetic, epigenetic and environmental factors. Currently, a growing yet heterogeneous body of evidence reports the development of concomitant CAD in identical twins; however, no systematic approach has been attempted so far to gather and quantify the existing evidence.

Methods
A systematic literature review was conducted by searching for original studies in PubMed, WebOfScience and Scopus databases through February 28, 2023 to identify every study reporting the incidence of CAD in monozygotic twin pairs according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and predetermined eligibility criteria (https://doi.org/10.17605/OSF.IO/TWXKP).

Results
Our search yielded 28 eligible studies encompassing a total of 37 monozygotic twin pairs suffering from CAD and presenting (simultaneously most of them) with acute coronary syndrome (mean age of presentation: 46 years, male percentage: 78%). Coronary angiograms demonstrated lesion and anatomy concordance at a 86% and 79% of the twin pairs, respectively. Concordance of the standard modifiable (environmental) cardiovascular risk factors was identified in at least 75% of the twin pairs, whereas only 4 genetic polymorphisms were identified (i.e., erythrocyte/leucocyte, ACE, LDLR, APOB genes and HLA polymorphisms).

Conclusion
This is the first systematic literature review of studies reporting identical twin pairs who suffer concomitantly from CAD. Most pairs shared similar environmental risk factors; however, their premature CAD could not be sufficiently explained in most cases leading us to speculate underlying (non-recognized) epigenetic interplay. Monozygotic twin studies -unbiased by age effects- can provide insights into CAD heritability on the grounds of their ability to disentangle the traditional dyad of genetic and environmental factors. Given the limited evidence on disease-causing mutations in the eligible studies, future twin studies are warranted to shed light on non-investigated genetic polymorphisms [such as lp(a)-related single nucleotide polymorphisms] and investigate the within-pair epigenetic drift through novel biomarkers of epigenetic regulation.PRISMA flow diagram of the reviewConcordance of CAD-related risk factors