Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2023;13(4):e2023201 1 Hidradenitis Suppurativa and Risk of Myocardial Infarction: A Plausible Association? Husein Husein-ElAhmed1,2, Martin Steinhoff2-6 1 Department of Dermatology and Venereology, Hospital de Baza, Granada, Spain 2 Translational Research Institute, Hamad Medical Corporation, Doha, Qatar 3 Department of Dermatology and Venereology, Hamad Medical Corporation, Doha, Qatar 4 Weill Cornell Medicine-Qatar, College of Medicine, Doha, Qatar 5 Qatar University, Medical School, Doha, Qatar 6 Deptartment of Dermatology, Weill Cornell Medicine, New York, NY, USA Key words: myocardial infarction, hidradenitis suppurativa, systemic inflammation, hazard rate, meta-analysis Citation: Hussein-ElAhmed H, Steinhoff M. Hidradenitis Suppurativa and Risk of Myocardial Infarction: A Plausible Association? Dermatol Pract Concept. 2023;13(4):e2023201. DOI: https://doi.org/10.5826/dpc.1304a201 Accepted: February 20, 2023; Published: October 2023 Copyright: ©2023 Hussein-ElAhmed et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Husein Husein-ElAhmed MD, PhD, Dept. of Dermatology and Venereology, Hospital de Baza, Granada, Spain. Phone: 0034605506589 FAX: 0034958023136 Email: huseinelahmed@hotmail.com Introduction Hidradenitis suppurativa (HS) is a chronic, inflammatory and relapsing skin disease. Cumulative evidence has estab- lished an association between HS and certain cardiovascular risk factors such as metabolic syndrome, diabetes, hypertri- glyceridemia and obesity. However, whether HS is an inde- pendent risk factor for myocardial infarction (MI) remains controversial. Objectives A systemic review and meta-analysis were conducted to ac- curately evaluate the association between HS and risk of MI. Eligible records comprised case-control, cross-sectional and cohort designs that compared rates of MI in HS to control groups. All studies without control groups (eg analysis of prevalence or assessment of comorbidity burden) were ex- cluded. Five databases (Pubmed, Scopus, Embase, Cochrane Library and clinicaltrial.gov) were searched. Two authors extracted independently the data of the studies. Results The search retrieved 15 records. After applying the inclusion criteria and removing duplicates, five records comprising 58.494 HS patients and 4.010.171 matched controls were finally analyzed. The complete flow chart of the literature search is depicted in Figure 1 and full references of the five included records are presented in the Supplementary File 1. The meta-analysis showed the relative risk of MI was simi- lar among both cohorts: 1.00 (95%CI: 0.49-2.02, I2=97%; Figure 2). To test the robustness of the meta-analysis, the combined results were recalculated by excluding one study 2 Research Letter | Dermatol Pract Concept. 2023;13(4):e2023201 per iteration. The exclusion of any single study did not alter the overall pooled outcome. Conclusions MI is mainly attributed to atherosclerosis. Atherosclerosis is a chronic inflammatory disease that shares precise pathways with HS such as overexpression of the T helper cell (Th)1/ (Th)17 [1]. Our work aggregates all available literature so far, and after pooling the largest cohort of HS patients, we found a negative correlation between HS and MI. The trim and fill sensitivity analysis did not change the general result, suggesting our outcome is not an artefact. Though analyses of hazard ratio were conducted independently of HS severity, this does not seem to affect the final result: Pinter et al ob- served the cardiovascular risk of MI in HS patients is largely attributed to smoking and not to HS-related processes such as chronic systemic inflammation [2]. In fact, these authors found matching for nicotine dependence reduced the risk of MI in HS subjects to almost levels of the control participants. Figure 1. Flow chart of data extraction and selection process throughout the databases. Figure 2. Forest plot of myocardial infarction in hidradenitis suppurativa individuals. Research Letter | Dermatol Pract Concept. 2023;13(4):e2023201 3 Accordingly, other authors noticed smoking is more frequent in severe HS patients and smoking increased likelihood of suffering from more severe HS form [3,4]. Together, these data indicate any potential increased incidence of MI related to severity of HS is driven more to the smoking habit rather than the enhanced systemic inflammation in severe HS. Along this line, a recent meta-analysis addressing this question have showed the odds ratio of MI of HS patients is similar to healthy controls, while the risk ratio from cohort studies cannot be assessed accurately due to the high hetero- geneity of the current evidence [5]. In psoriasis which shares immunological characteristics with HS, such as Th1/Th17 pathways and involvement of TNF-alpha, a meta-analysis showed slight increased risk of MI with an overall relative risk of 1.22 [3,6]. Unlike psori- asis, this work shows HS does not influence the coronary arterial vessels, possibly due to differences in the pathologi- cal inflammatory pathways acting on blood vessels. In sup- port of this, any potential clinical impact of HS to vascular function in precise areas of the arterial and venous vascular system such as brain or lower extremities can be soundly questioned according to recent reports in which hazards of stroke, arterial peripheral disease and venous thromboem- bolia were comparable to controls [7]. In sum, all these data indicate the HS-related chronic inflammation is not a trigger of cardiovascular comorbidities, but other factors and be- haviors may play a more dominant role. The major strength of our work is the sample size and the statistical power. On the basis of their characteristics, all included records can be considered good quality, well- conducted studies with long follow-up, reliable exposure and outcome assessment: most of patient groups comprised hospital-based individuals diagnosed of HS by dermatolo- gists. Thus, potential misdiagnosis is minimized. Addition- ally, hospital and population-based patients differ from each other since the former may have more severe forms of HS and eventually, higher probability of cardiovascular comor- bidities; hence, the significant negative association is stron- ger. Finally, four records of the meta-analysis consisted of general population instead of hospital controls, and although the comparability of hospital versus population controls has not been explored in detail in case-control studies for HS, it is feasible to assume the matched-controls from general pop- ulation are healthier than hospital controls, and thus, any negative correlation is even more robust. On summary, the association between HS and MI is not evident from current literature and has yet to be elucidated. Further research is warranted to clarify as to whether the HS population have an increased trend of suffering from this major cardiovascular event. References 1. Schlapbach C, Hänni T, Yawalkar N, Hunger RE. Expression of the IL-23/Th17 pathway in lesions of hidradenitis suppura- tiva. J Am Acad Dermatol. 2011;65(4):790-798. DOI: 10.1016/j .jaad.2010.07.010. PMID: 21641076. 2. Pinter A, Kokolakis G, Rech J, et al. Hidradenitis Suppurativa and Concurrent Psoriasis: Comparison of Epidemiology, Co- morbidity Profiles, and Risk Factors. Dermatol Ther (Heidelb). 2020;10(4):721-734. DOI: 10.1007/s13555-020-00401-y. PMID: 32500484. PMCID: PMC7367943. 3. Sartorius K, Emtestam L, Jemec GB, Lapins J. Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smok- ing and obesity. Br J Dermatol. 2009;161(4):831-839. DOI: 10.1111/j.1365-2133.2009.09198.x. 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