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ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 68
| Issue : 4 | Page : 359-365 |
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| Hidradenitis suppurativa and risk of coronary artery disease: A systematic review and meta-analysis |
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Pitchaya Worapongsatitaya1, Thanat Chaikijurajai2, Ben Ponvilawan3, Patompong Ungprasert4
1 From the Internal Medicine Residency Program, University of Minnesota Medical School, Minneapolis, MN, USA
2 From the Internal Medicine Residency Program, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand
3 Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
4 Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH, USA
| Date of Web Publication | 31-Aug-2023 |
Correspondence Address:
Patompong Ungprasert
Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, 9500 Euclid Avenue, Cleveland - 44195, Ohio
USA
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijd.ijd_245_22
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 Abstract | | |
Background: Patients with hidradenitis suppurativa (HS) may have a higher risk of coronary artery disease (CAD) due to the excessive inflammatory burden. However, data on this association is still relatively limited. Aims: To investigate the association between HS and risk of prevalent and incident CAD by combining result from all available studies using systematic review and meta-analysis technique. Materials and Methods: Potentially eligible studies were identified from Medline and EMBASE databases from inception to November 2021 using search strategy that comprised of terms for 'hidradenitis suppurativa' (HS) and 'coronary artery disease' (CAD). Eligible study must be cohort study that consisted of one cohort of patients with HS and another cohort of individuals without HS. The study must report incidence or prevalence of CAD in both groups. The retrieved point estimates with standard errors from each study were summarized into pooled result using random-effect model and generic inverse variance method. Meta-analyses of the prevalent and incident CAD were conducted separately. Results: A total of 876 articles were identified. After two rounds of independent review by three investigators, seven cohort studies (four incident studies and three prevalent studies) met the eligibility criteria and were analysed in the meta-analyses. The meta-analysis found a significantly elevated risk of both incident and prevalent CAD in patients with HS compared to individuals without psoriasis with the pooled risk ratio of 1.38 (95% CI, 1.21–1.58; I2 83%) and 1.70 (95% CI, 1.13–2.57; I2 89%), respectively. Limitations: Limited accuracy of diagnosis of HS and CSD as most included studies relied on diagnostic codes and high between-study statistical heterogeneity. Conclusions: The current systematic review and meta-analysis found a significantly increased risk of both prevalent and incident CAD among patients with HS.
Keywords: Coronary artery disease, hidradenitis suppurativa, meta-analysis
How to cite this article:
Worapongsatitaya P, Chaikijurajai T, Ponvilawan B, Ungprasert P. Hidradenitis suppurativa and risk of coronary artery disease: A systematic review and meta-analysis. Indian J Dermatol 2023;68:359-65 |
How to cite this URL:
Worapongsatitaya P, Chaikijurajai T, Ponvilawan B, Ungprasert P. Hidradenitis suppurativa and risk of coronary artery disease: A systematic review and meta-analysis. Indian J Dermatol [serial online] 2023 [cited 2023 Sep 24];68:359-65. Available from: https://www.e-ijd.org/text.asp?2023/68/4/359/384843 |
| Introduction | |  |
The causative role of chronic inflammation in the development of premature atherosclerosis is well-recognized.[1],[2] Several studies have demonstrated the deleterious effects of inflammatory cytokine, reactive oxygen species and activated leukocytes on endothelial function, resulting in the initiation and progression of atherosclerotic plaque.[3],[4],[5],[6] Both in vivo and in vitro studies have demonstrated hypercoagulable state associated with chronic inflammation as a result of activated coagulation cascade as well as impaired anti-coagulation pathway and fibrinolysis.[7],[8] These factors may serve as the foundation of the development of significant compromised coronary arterial blood flow and clinically evident coronary artery disease (CAD). Moreover, an increased incidence and prevalence of CAD among patients with inflammatory disorders, such as rheumatoid arthritis, psoriasis and systemic lupus erythematosus and polymyalgia rheumatica, have been reported.[9],[10],[11],[12],[13]
Hidradenitis suppurativa (HS) is a chronic skin disorder characterized by recurrent inflammation of the pilosebaceous unit. HS usually presents as inflammatory nodules in intertriginous areas that can progress to abscesses, fistula, scarring and contractures.[14] It is a relatively common disease with the reported prevalence of approximately 0.1% with female to male ratio of 2:1.[15]
Due to the higher inflammatory burden, patients with HS may also carry a higher risk of CAD similar to other chronic inflammatory disorders. The current systematic review and meta-analysis aim to comprehensively review and summarize the results of all available studies that compare the incidence and prevalence of CAD among patients with HS versus individual without HS.
| Materials and Methods | | |
Search strategy
Published studies indexed in Medline and EMBASE database from inception to November 2021 were independently reviewed by two investigators (T.C. and P.W.). Search strategy was developed using terms associated with HS and CADs. The search strategy is described in detail in Supplemental Material 1. No language restriction was applied.
Inclusion criteria
Eligible study must be cohort study that consisted of one cohort of patients with HS and another cohort of individuals without HS. The study must report incidence or prevalence of CAD in both groups. Alternatively, the study may report relative risk (RR), hazard risk ratio (HR), standardized incidence ratio (SIR) or incidence rate ratio (IRR) with associated 95% confidence interval (CI) comparing the incidence or prevalence of CAD between the two groups.
The same two investigators independently reviewed each retrieved study for its eligibility. Difference in the determination of study eligibility was resolved by discussion with the senior investigator (P.U.). The quality of studies that reported incident CAD was assessed by two investigators (P.U. and P.W.) using the Newcastle-Ottawa quality assessment scale for cohort study.[16]
Data extraction
A standardized data collection form was utilized for extraction of the following data from each included study: last name of the first author, country where the study was conducted, year (s) of study, publication year, number of participants, recruitment of participants, diagnosis of HS, diagnosis of CAD, average follow-up duration (for incident study), mean age of participants, percentage of female participants, comorbidities of participants and variables that were adjusted in multivariate analysis.
Statistical analysis
Review Manager 5.3 software from the Cochrane Collaboration was used for all of the analyses. Point estimates with standard errors were extracted from each study and were combined to calculate pooled effect estimates using the generic inverse variance method as described by DerSimonian and Laird.[17] Random-effect model, instead of fixed-effect model, was used as the underlying assumption of fixed-effect model that every study should yield the same effect estimate is almost always not true for meta-analysis of observational study. Meta-analyses of the prevalent and incident CAD were conducted separately. Cochran's Q test and I2 statistic were used to assess between-study heterogeneity. A value of I2 of 0–25% represents insignificant heterogeneity, 26–50% low heterogeneity, 51–75% moderate heterogeneity and >75% high heterogeneity.[18] We planned to create funnel plot to assess for the presence of publication bias if there were enough eligible studies.
| Results | | |
Search results
A total of 876 articles were retrieved from EMBASE and Medline database using the aforementioned search strategy. There were 82 duplicated articles between the two databases which were eliminated, leaving 794 articles for title and abstract review. At this stage, 761 articles were eliminated as they obviously did not meet the eligibility criteria based on study design and type of article. This left a total of 33 articles for the full-length article review. After full-length review, 26 articles were further eliminated as they did not report the outcome of interest. Finally, seven cohort studies (four incident studies[19],[20],[21],[22] and three prevalent studies[23],[24],[25]) met the eligibility criteria and were analysed in the meta-analyses. [Figure 1] demonstrates the systematic review process of this study. [Table 1] and [Table 2] describe the methodology and baseline characteristics of the included cohort studies for incident and prevalent meta-analysis, respectively. | Table 1: Main characteristics of the cohort studies included in the meta-analysis of incident CAD in hidradenitis suppurativa
Click here to view |
 | Table 2: Main characteristics of the cohort studies included in the meta-analysis of prevalent CAD in hidradenitis suppurative
Click here to view |
Risk of incident coronary artery disease in patients with hidradenitis suppurativa
The meta-analysis found a significantly elevated risk of incident CAD in patients with HS compared to individuals without HS with the pooled risk ratio of 1.38 (95% CI, 1.21–1.58). This meta-analysis had high statistical heterogeneity with I2 of 83% [Figure 2]. | Figure 2: Forest plot of the meta-analysis of risk of incident coronary artery disease in patients with hidradenitis suppurativa
Click here to view |
Risk of prevalent coronary artery disease in patients with hidradenitis suppurativa
The meta-analysis found a significantly elevated risk of prevalent CAD in patients with HS compared to individuals without HS with the pooled risk ratio of 1.70 (95% CI, 1.13–2.57). This meta-analysis had high statistical heterogeneity with I2 of 89% [Figure 3]. | Figure 3: Forest plot of the meta-analysis of risk of prevalent coronary artery disease in patients with hidradenitis suppurativa
Click here to view |
Evaluation for publication bias
Funnel plot for assessment of publication bias was not created due to the limited number of eligible studies for both meta-analyses.
| Discussion | | |
The current systematic review and meta-analysis summarizes data from seven studies, involving over 80,000 patients with HS. There was a significantly increased risk of both incident and prevalent CAD among patients with HS compared with individuals without HS. All included studies reported a positive association between HS and CAD, but the risk estimates varied considerably, ranging from 1.3 to 2.7-fold increase.
Premature atherosclerosis as a result of excessive inflammatory burden is probably the main pathogenesis behind the increased risk of CAD among patients with HS.[7],[8] Studies have demonstrated that inflammatory cytokines, such as interleukin-1 and tumour necrosis factor, can induce the expression of vascular adhesion molecule-1 (VCAM-1) in endothelial cells, which could promote adhesion and invasion of monocytes to vascular endothelium and tunica intima.[2],[26] Subsequently, those monocytes would internalize and oxidize lipoprotein particle, initiating the process of lipid deposition and plaque formation in the arterial wall. Chronic inflammation also weakens atherosclerotic plaque through the activated leukocytes and increased production of enzymes that could degrade extracellular matrix constituents such as matrix metalloproteinases (MMPs).[27] This would make the plaque more vulnerable to rupture and, thus, increased risk of acute myocardial infarction. Furthermore, chronic inflammation is known to induce hypercoagulable state through activated coagulation cascade and compromised fibrinolytic pathway.[7],[8]
The second explanation is related to shared risk factors between HS and CAD. Smoking and obesity are ones of the most important non-genetic risk factors of HS.[14],[28] The role of smoking and obesity in the pathogenesis of CAD is well-established.[29]
Glucocorticoids, a commonly used medication for the management of HS may also serve as a contributing factor to the increased cardiovascular disease risk as their long-term exposure is associated with several predisposing factors for coronary heart disease, such as diabetes mellitus, hypertension and dyslipidemia.[30]
This study has some limitations, and therefore, the pooled results should be interpreted with caution. First, most of the included studies were conducted using administrative database.
Diagnoses of HS and CAD were made based on the presence of diagnostic codes with no further verification which would jeopardize the accuracy of the identification of cases and event of interest. Second, the between-study heterogeneity was high in both meta-analyses which is likely caused by different methodology and background population. Third, the possibility of publication bias could not be assessed due to small numbers of available studies. Therefore, publication bias in favour of studies that showed positive association may have been present.
| Conclusion | | |
In summary, the current systematic review and meta-analysis found a significantly increased risk of both prevalent and incident CAD among patients with HS.
Financial support and sponsorship
We did not receive any specific grant from funding agencies in the commercial, public or not-for-profit sectors.
Conflicts of interest
We do not have any financial or nonfinancial potential conflict of interest.
| Supplemental Material 1 – Searching strategy | | |
EMBASE Database
- 'suppurative hidradenitis'/exp OR 'suppurative hidradenitis'
- 'hidradenitis suppurativa'/exp OR 'hidradenitis suppurativa'
- 'acne inversa'/exp OR 'acne inversa'
- velpeau
- 'verneuil disease'/exp OR 'verneuil disease'
- 'heart infarction'/exp OR 'heart infarction'
- 'coronary artery disease'/exp OR 'coronary artery disease'
- 'heart muscle ischemia'/exp OR 'heart muscle ischemia'
- 'st segment elevation myocardial infarction'/exp OR 'st segment elevation myocardial infarction'
- 'non st segment elevation myocardial infarction'/exp OR 'non st segment elevation myocardial infarction'
- 'unstable angina pectoris'/exp OR 'unstable angina pectoris'
- 'chronic stable angina'/exp OR 'chronic stable angina'
- 'stable angina pectoris'/exp OR 'stable angina pectoris'
- 'acute coronary syndrome'/exp OR 'acute coronary syndrome'
- 'ischemic heart disease'/exp OR 'ischemic heart disease'
- 'cardiovascular disease'/exp OR 'cardiovascular disease'
- #1 OR #2 OR #3 OR #4 OR #5
- #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16
- #17 AND #18
Ovid Medline Database
- hidradenitis suppurativa.mp. or exp Hidradenitis Suppurativa
- suppurative hidradenitis.mp.
- acne inversa.mp.
- velpeau.mp.
- verneuil's disease.mp.
- coronary artery disease.mp. or exp Coronary Artery Disease/
- myocardial infarction.mp. or exp Myocardial Infarction/
- myocardial ischemia.mp. or exp Myocardial Ischemia/
- st segment elevation myocardial infarction.mp. or exp ST Elevation Myocardial Infarction/
- non st segment elevation myocardial infarction.mp. or exp Non-ST Elevated Myocardial Infarction/
- unstable angina.mp. or exp Angina, Unstable/
- chronic stable angina.mp. or exp Angina, Stable/
- acute coronary syndrome.mp. or exp Acute Coronary Syndrome/
- ischemic heart disease.mp.
- coronary heart disease.mp. or exp Coronary Disease/
- cardiovascular disease.mp. or exp Cardiovascular Diseases/
- 1 or 2 or 3 or 4 or 5
- 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16
- 17 and 18
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2] |
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