
==== Front
Ann Med
Ann Med
Annals of Medicine
0785-3890
1365-2060
Taylor & Francis

39300810
10.1080/07853890.2024.2326297
2326297
Version of Record
Review Article
Dermatology
Risk factors for cardiovascular diseases in patients with vitiligo: an analysis of current evidence
X. Liang et al.
Liang Xin a#
Guo Fei b#
Zhang Miao bc
Wang Chunxiao bc
Lin Naixuan bc
Liu Li a
Chen Yan a
Liu Fang a
Du Yuhua a
Li Lei a
Li Xin abc
a Chinese Medicine Department, Songnan Town Community Health Service Center, Shanghai, China
b Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
c Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Supplemental data for this article can be accessed online at https://doi.org/10.1080/07853890.2024.2326297.

# These authors have contributed equally to this work

CONTACT Xin Li 13661956326@163.com
Lei Li 2622900954@qq.com Chinese Medicine Department, Songnan Town Community Health Service Center, Shanghai, 200441, China.
19 9 2024
2024
19 9 2024
56 1 23262973 2 2023
7 2 2024
16 2 2024
KnowledgeWorks Global Ltd.12 9 2024
published online in a building issue12 9 2024
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
2024
The Author(s)
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

Abstract

Objective

The relationship between vitiligo and cardiovascular diseases remains controversial. This study aimed to systematically review the evidence comparing cardiovascular disease risk factors between patients with vitiligo and controls and to perform a meta-analysis of the results.

Data sources

A comprehensive database search was performed for all studies in PubMed, EMBASE, and Cochrane Central Register databases from inception to November, 2023. The main keywords used were vitiligo, hypertension, diabetes, hyperlipidemia, metabolic syndrome, obesity, smoking, alcohol consumption, C-reactive protein, and homocysteine.

Study selection

Only observational studies and no randomized controlled trials were included. Of the 1269 studies initially selected, the full texts of 108 were assessed for eligibility, and 74 were ultimately included in the analysis.

Data extraction and synthesis

Three reviewers independently extracted the following data: study design, number and characteristics of participants, inclusion indicators, and disease duration. A meta-analysis of the single-group rates was performed for the diabetes, hypertension, hyperlipidemia, and obesity groups. Random-effects or fixed-effects models were used to calculate the sample-size weighted averages for the indicators included in the studies.

Main outcomes and measures

The primary outcomes were co-morbidity analysis and co-morbidity rates of vitiligo with metabolic syndrome, obesity, hyperlipidemia, hypertension, and diabetes mellitus. Secondary outcomes were factors associated with vitiligo and cardiovascular disease.

Results

This meta-analysis concluded that comorbidities in patients with vitiligo included metabolic syndrome, diabetes, obesity, hyperlipidemia, and hypertension, with comorbidity rates of 28.3%, 6.0%, 38.5%, 43.0%, and 15.8%, respectively. Simultaneously, we showed that the vitiligo group differed significantly from the control group in the following aspects: fasting blood glucose, insulin, systolic and diastolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, homocysteine, C-reactive protein, smoking, and alcohol consumption. However, no significant differences were observed between the vitiligo and control groups in terms of waist circumference, body mass index, or phospholipid levels.

Limitations

The vast majority of the studies were from Eastern countries; therefore, extrapolation of these results to Western populations is questionable. The significant heterogeneity may be due to different protocols, doses, durations, center settings, population registries, etc., which severely compromise the validity of the results.

Conclusion

This study summarized not only the factors associated with, but also those not associated with, cardiovascular disease in patients with vitiligo. This study provides a foundation for the prevention and treatment of cardiovascular disease in patients with vitiligo.

KEY MESSAGES

The relationship between vitiligo and cardiovascular diseases remains controversial.

This meta-analysis concluded that comorbidities in patients with vitiligo include metabolic syndrome, diabetes, obesity, hyperlipidemia, and hypertension, with comorbidity rates of 28.3%, 6.0%, 38.5%, 43.0%, and 15.8%.

Our study identified cardiovascular disease risk factors in patients with vitiligo, including smoking, alcohol consumption, high serum SBP, DBP, FBG, CRP, TC, TG, LDL, insulin, and Hcy, and low serum HDL levels.

Keywords

Vitiligo
cardiovascular disease risk
diabetes
obesity
hyperlipidemia
hypertension
systematic review
the National Natural Science Foundation of Shanghai Science and Technology Commission of Baoshan District, Shanghai Medical Health Project This work was supported by the Shanghai Pujiang Program (grant 33 no. 2020PJD067), National Natural Science Foundation of Shanghai (Grant No. 19ZR1458700), Science and Technology Commission of Baoshan District, Shanghai Medical Health Project (Grant No. 21-E-33), Key Discipline Construction Project of Shanghai’s Three Year Action Plan for Strengthening the Construction of Public Health System (Grant No. GWVI-11.1-24); High-level Chinese Medicine Key Discipline Construction Project (Integrative Chinese and Western Medicine Clinic) of National Administration of TCM (Grant No. zyyzdxk-2023065); Shanghai Three-Year Action Plan to Further Accelerate the Inheritance and Innovative Development of Chinese Medicine (2021–2023) (Grant No. ZY(2021-2023)-0302), New round (2023-2025) Baoshan Medical key (specialized) Department "Vitiligo, hair loss integrated Traditional Chinese and Western medicine characteristic Treatment Clinic"(Grant No. BSZK-2023-A15), Li Bin Shanghai famous Chinese medicine studio grassroots workstation(Grant No. JCGZZ-2023078), 2023 Shanghai Traditional Chinese Medicine Specialty Capacity Construction "Traditional Chinese Medicine Dermatology"(Grant No. SQZBZK-23-25)
==== Body
pmcIntroduction

Vitiligo is a common, acquired depigmentation disorder that results in spots or flaky white patches on the skin caused by the loss of melanocytes. The incidence of vitiligo is approximately 0.1–2% globally, and men and women are equally affected, with no racial difference [1–7]. The international consensus classifies vitiligo into two types: segmental and nonsegmental. The latter category includes generalized, focal, acrofacial, mucosal and universal [8]. Nonsegmental vitiligo is clinically characterized by depigmented patches with a diameter of a few centimeters, usually involving both sides of the body in a symmetrical manner. Segmental vitiligo develops rapidly but has a limited course; depigmentation spreads within the segments in 6–24 months and ceases gradually with further expansion rarely seen [9].

The pathogenesis of vitiligo has not yet been confirmed, and the current evidence suggests that it may be related to oxidative stress, genetic factors, degenerative theory, autoimmune responses, generation of inflammatory mediators, and melanocyte detachment mechanisms [9–11]. Vitiligo is often associated with autoimmune diseases, particularly autoimmune thyroid diseases (Hashimoto’s thyroiditis and Graves’ disease), rheumatoid arthritis, diabetes, psoriasis, pernicious anemia, systemic lupus erythematosus, and Addison’s disease [12–14]. Tumor necrosis factor-α, interleukin-1, and interleukin-6 are cytokines that promote inflammatory responses. They have been implicated in the pathogenesis of vitiligo and are associated with insulin resistance, atherosclerosis, and other metabolic complications [15].

Few studies have suggested that patients with vitiligo might be at a higher risk of dyslipidemia and atherosclerosis, thus increasing their risk for cardiovascular diseases [13, 16,17]. Additionally, patients with vitiligo, especially those with chronic and severe diseases or concomitant metabolic syndromes, are at an increased risk of cardiovascular diseases [18]. An Iranian study concluded that individuals with vitiligo were more likely to develop high blood pressure, which is a risk factor for cardiovascular diseases [19], while other studies considered patients with vitiligo to have a lower risk for cardiovascular diseases [20].

Considering the controversial reports on the relationship between vitiligo and cardiovascular diseases and whether patients with vitiligo are at a higher risk of cardiovascular disease than healthy controls, a systematic review and meta-analysis are urgently needed to illustrate this relationship, increase our understanding of the strength of their correlation, and provide updated data references for performing relevant medical services and clinical interventions. This systematic review is the first to systematically summarize the factors associated with and unrelated to the risk of cardiovascular diseases in patients with vitiligo.

Materials and methods

We performed a systematic review and meta-analysis to assess the association between vitiligo and cardiovascular disease risk factors. This study was conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and registered with PROSPERO (CRD42023390952), an international registry for prospective systematic evaluations (https://www.crd.york.ac.uk/PROSPERO/).

Data sources and searches

PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to November, 2023, for studies on the association between vitiligo and cardiovascular disease risk factors. We added the term ‘vitiligo’ to the keywords of risk factors, including ‘diabetes’, ‘hypertension’, ‘homocysteine’, ‘LDL’, ‘HDL’, ‘C-reactive protein’, ‘metabolic syndrome’, ‘fasting glucose’, ‘triglycerides’, ‘cholesterol’, ‘body mass index’, ‘obesity’, and other keywords for database search. This review was limited to studies published in English.

Inclusion and exclusion criteria

The included studies were selected according to the following criteria: (1) human studies only; (2) provide raw data; (3) include a reference group, single-arm studies to calculate disease incidence; (4) provide odds ratio (OR), hazard ratio, or hazard ratio estimates and confidence intervals (CIs) (or sufficient data to calculate them); and treat cardiovascular disease (atherosclerosis, acute coronary syndrome) and its risk factors as specific outcome events. The exclusion criteria were as follows: (1) multiple submissions, (2) not a clinical study, and (3) inability to contact the corresponding author. Initially, 708 articles were included (Figure 1). Three additional articles were identified after a manual review of the reference lists of the selected studies. These studies were then carefully reviewed. Finally, 74 studies were included in this systematic review (Table 1). A flowchart describing the screening process is shown in Figure 1.

Figure 1. Literature search and study selection.

Figure 2. Cardiovascular risk factors in patients with vitiligo.

Vitiligo patients have high serum fasting glucose, insulin, total cholesterol, triglycerides, low-density lipoproteins, C-reactive protein, and homocysteine levels; smoking and alcohol consumption increase the risk of cardiovascular disease in patients with vitiligo.

Table 1. Characteristics of the included studies and the Newcastle–Ottawa scale (NOS) quality assessment table.

Author (pub. year)	Study setting	Study period	Study design	Indicators used in the study	Controls: total number	Cases: total number	Mean age of controls, years, mean (SD)	Mean age of cases, years, mean (SD)	Disease duration, mean (SD)	Controls gender M/F	Cases gender M/F	Controls BMI, mean (SD)	Cases BMI, mean (SD)	VETI score	NOS score	
Demirbas et al. 2021[21]	Turkey; NR	1/2019–12/2019	Case control	HDL	Total: 180	Total: 180	35.7 (7.39)	29.56 (9.8)	7.42 (7.48)	90/90	87/93	NR	NR	2.8 (3.13)	8	
D’arino et al. 2021[22]	Italy; NR	1/2017–1/2021	Case control	TG, TC, FBG, HDL, LDL	Total: 316	Total: 839	NR	45.3 (15.5)	NR	124/192	351/488	NR	NR	NR	7	
Pietrzak et al. 2014[23]	Italy; NR	NR	Case control	BMI	Total: 35	Total: 34	10.5 (2.3)	10.9 (2.0)	2.1 (0.8)	16/19	21/13	17.6 (2.8)	17.0 (2.1)	NR	8	
Nejad et al. 2013[14]	Iran; NR	NR	Case control	Diabetes	Total: 77	Total: 86	NR	28.11 (12.5)	NR	NR	52/33	NR	NR	NR	7	
Afkhami-Ardekani et al. 2014[24]	Iran; NR	6 months	Cross sectional	Diabetes	Total: 1100	Total: 1100	NR	NR	NR	NR	NR	NR	NR	NR	8	
Al Fahaad et al. 2015[25]	Saudi Arabia; outpatient	1/2012–7/2012	Cross sectional	Hypertension, diabetes	NR	Total: 101	NR	NR	NR	NR	58/43	NR	NR	NR	5	
Al Houssien et al. 2017[26]	Saudi Arabia; NR	1/2016–9/2016	Case control	Hypertension, diabetes, obesity	Total: 61	Total: 61	40 (17)	45 (19)	NR	17/44	17/44	NR	NR	NR	7	
Al-Mutairi et al. 2011[27]	Kuwait; NR	1/1005–12/2008	Prospective study	Diabetes	Total: 197	Total: 100	NR	NR	NR	NR	95/102	NR	NR	NR	4	
Anbar et al. 2016[28]	Egypt; outpatient	11/2011–2012	Case control	Hcy	Total: 30	Total: 30	NR	NR	NR	12/18	13/17	NR	NR	NR	8	
Aryanian et al. 2022[29]	Iran; NR	4/2018–3/2019	Case control	BMI, SBP, DBP, CRP, TG, TC, HDL, LDL	Total: 40	Total: 40	37.50 (7.16)	37.95 (9.25)	NR	21/19	17/23	24.42(2.71)	24.61(3.04)	NR	8	
Atas et al. 2015[30]	Turkey; NR	2011–2013	Case control	Hcy	Total: 60	Total: 60	36.25 (7.8)	35.7 (11.2)	NR	30/30	30/30	NR	NR	NR	8	
Atas et al. 2017[31]	Turkey; outpatient	NR	Case control	Hypertension, Mts, hyperlipidemia, SBP, DBP, Waist circumference, TG, HDL, FBG	Total: 65	Total: 63	40.3 (10.3)	40.1 (11.8)	NR	31/34	30/33	NR	NR	NR	7	
Azzazi et al. 2021[13]	Egypt; NR	12/2018–1/2020	Case control	TG, TC, HDL, LDL	Total: 50	Total: 50	40.02 (14.561)	NR	NR	NR	23/27	NR	NR	NR	7	
Birlea et al. 2006[32]	Romania; Community Residents	2002–2004	Cross-sectional	Diabetes	Total: 33	Total: 31	NR	NR	NR	NR	10/21	NR	NR	NR	8	
Birlea et al. 2008[33]	Romania; Community Residents	1/2001–2/2006	Cross-sectional	Diabetes	NR	Total: 51	NR	NR	NR	NR	NR	NR	NR	NR	8	
Butt et al. 2015[34]	Lahore; outpatient	NR	Cross-sectional	Diabetes	NR	Total: 100	NR	NR	NR	NR	54/46	NR	NR	NR	2	
Chen et al. 2016[35]	China; NR	NR	Case control	Hcy	Total: 80	Total: 80	NR	NR	NR	 	 	 	 	NR	7	
Demir et al. 2014[36]	Turkey; NR	NR	Case control	TG, TC, HDL, LDL, FBG, BMI, insulin, HOMA-IR	Total: 30	Total: 30	32.40 (6.9)	28.66 (11.6)	NR	15/15	15/15	23.84 (1.45)	23.22(1.65)	NR	7	
Demirbas et al. 2021[21]	Turkey; NR	1/2019–12/2019	Case control	HDL	Total: 180	Total: 180	29.61 (9.66)	29.56 (9.8)	7.42 (7.48)	90/90	87/93	NR	NR	2.8 (3.13)	8	
Derakhshandeh-Rishehri et al. 2019[37]	Iran; NR	NR	Case control	BMI, TC	Total: 110	Total: 100	23.22 (5.39)	20.71 (6.19)	NR	62/33	38/68	23.31(5.86)	21.48(2.68)	NR	8	
El Tahlawi et al. 2020[38]	Egypt; NR	9/2013–10/2014	Case control	Hcy	Total: 80	Total: 100	NR	34.96 (13.842)	6.20 (6.061)	20/60	20/80	NR	NR	NR	8	
Farag et al. 2022[39]	Egypt; outpatient	NR	Case control	Mts, BMI, SBP, DBP, TG, HDL, FBG, TC	Total: 45	Total: 45	32.89 (13.56)	35.51 (15.98)	4.69 (4.89)	27/28	25/20	23.89 (2.4)	29.53 (5.02)	NR	7	
Gönül et al. 2012[40]	Turkey; NR	NR	Retrospective study	Diabetes Hypertension	NR	Total: 93	NR	37.4 (17.05)	NR	NR	49/44	NR	NR	NR	3	
Gopal et al. 2014[41]	India; NR	1/2008–12/2008	Case-control study	Diabetes	Total: 100	Total: 150	NR	NR	NR	54/46	83/67	NR	NR	NR	6	
Gopal et al. 2007[42]	India; NR	4/2004–12/2004	Case-control study	Diabetes	Total: 100	Total: 150	NR	NR	NR	NR	NR	NR	NR	NR	6	
Gorial et al. 2021[43]	Iraq; NR	9/2018–5/2019	Case-control study	BMI, smoking	Total: 63	Total: 63	39.9 (11.6)	38.7 (14.0)	13.3 (12.7)	30/33	34/29	30.6 (5.7)	27.6 (7,4)	NR	7	
Gupta et al. 2016[44]	India; NR	11/2011–8/2012	Case-control study	Hcy	Total: 83	Total: 82	31.27 (0.87)	30.56 (0.85)	2.09 (0.09)	45/38	50/32	NR	NR	NR	7	
Handa et al. 2003[45]	India; NR	1990–1999	Retrospective study	Diabetes	NR	Total: 625	NR	NR	NR	NR	NR	NR	NR	NR	2	
Handa et al. 1999[46]	India; NR	2/1989–2/1993	Retrospective study	Diabetes	NR	Total: 1436	NR	NR	NR	NR	783/653	NR	NR	NR	2	
Karadag et al. 2011[47]	Turkey; NR	NR	Case-control study	BMI, TC, HDL, LDL, waist circumference	Total: 39	Total: 57	40.2 (11.1)	38.5 (14.2)	NR	28/11	31/26	31.1 (17.8)	30.0 (15.6)	NR	6	
Mubki et al. 2017[48]	Saudi Arabia; NR	7/2014–12/2015	Case-control study	FBG	Total: 89	Total: 115	30.73 (10.56)	29.53 (9.22)	NR	37/52	51/64	NR	NR	NE	7	
Nahidi et al. 2014[49]	Iran; NR	NR	Case-control study	Hcy	Total: 40	Total: 50	NR	NR	NR	NR	23/17	NR	NR	NR	6	
Naik et al. 2010[50]	India; NR	2 months	Descriptive research	Hypertension	NR	Total: 60	NR	NR	NR	NR	25/35	NR	NR	NR	2	
Namazi et al. 2020[19]	Iran; outpatient	6/2019–9/2019	Case-control study	Hypertension	Total: 83	Total: 83	NR	NR	NR	50/33	50/33	NR	NR	NR	7	
Namazi et al. 2021[18]	Iran; NR	11/2016–2/2018	Case-control study	TG, TC, HDL, LDL, FBG, BMI, SBP, DBP, waist circumference	Total: 70	Total: 70	38.86 (11.4)	37.61 (12.27)	9.69 (7.07)	NR	NR	25.01 (3.32)	26.17 (4.91)	NR	7	
Narita et al. 2011[51]	Japan; NR	NR	Descriptive research	Diabetes	NR	Total: 133	NR	49.3 (19.8)	8.2 (8.6)	NR	57/76	NR	NR	NR	2	
P. K. Sinha et al. 2019[52]	India; NR	NR	Case-control study	TG, TC, HDL, LDL, FBG, BMI, SBP, DBP, waist circumference	Total: 75	Total: 75	NR	NR	NR	NR	NR	NR	NR	NR	6	
Pietrzak et al. 2000[53]	Lublin; NR	NR	Case-control study	TG, TC, HDL, LDL, BMI, Ph	Total: 19	Total: 11	10.05 (2.25)	10.91 (2.38)	NR	NR	NR	17.51 (3.34)	17.62 (1.96)	NR	5	
Sallam et al. 2017[54]	Egypt; outpatient	NR	Case-control study	HOMA-IR, insulin, Mts, TG, TC, HDL, LDL, FBG, BMI, SBP, DBP, waist circumference	Total: 89	Total: 102	34.53 (11.97)	32.73 (16.27)	NR	33/56	40/62	30.75 (4.49)	27.51 (5.54)	NR	7	
Salman et al. 2016[55]	Babylon-Iraq; outpatient	11/2015–3/2016	Case-control study	Hcy	Total: 44	Total: 44	27.56 (4.55)	27.82 (4.94)	10.73 (6.48)	26/18	25/19	NR	NR	NR	7	
Shahzad et al. 2014[56]	Iran; outpatient	2009–2010	Case-control study	Diabetes	Total: 70	Total: 70	NR	NR	NR	NR	NR	NR	NR	NR	5	
Shaker et al. 2008[57]	Egypt; NR	NR	Case-control study	Hcy	Total: 26	Total: 26	33.04 (6.37)	31.4 (8.09)	NR	NR	NR	NR	NR	NR	6	
Sharma et al. 2017[58]	India; NR	NR	Case-control study	Mts, TG, HDL, FBG, BMI, SBP, DBP, waist circumference, smoking, alcohol	Total: 100	Total: 100	42.3 (11.5)	43.5 (10.5)	NR	64/36	66/34	23.91 (3.66)	24.13 (3.75)	NR	6	
Sheth et al. 2014[59]	USA; NR	1/1/2000–1/6/2010	Descriptive research	Diabetes	NR	Total: 2441	NR	NR	NR	NR	836/1137	NR	NR	NR	3	
Singh et al. 2014[60]	India; NR	NR	Case-control study	BMI, TG, insulin	Total: 30	Total: 35	NR	NR	NR	NR	NR	21.79 (2.51)	25.18 (4.59)	NR	5	
Singh et al. 2020[17]	India; NR	NR	Case-control study	CRP,	Total: 30	Total: 35	NR	NR	NR	NR	NR	NR	NR	NR	5	
Singh et al. 2020[61]	India; NR	NR	Case-control study	BMI	Total: 30	Total: 35	NR	NR	NR	NR	NR	21.79(2.51)	25.18 (4.59)	NR	5	
Singh et al. 2011[62]	India; outpatient	NR	Case-control study	Hcy	Total: 30	Total: 30	NR	NR	NR	NR	16/14	NR	NR	NR	5	
Tanacan et al. 2020[63]	Turkey; NR	11/2014–3/2016	Cross-sectional study	Diabetes, hypertension, hyperlipidemia, obesity, smoking, alcohol, Mts, TG, HDL, LDL, FBG, BMI, SBP, DBP, CRP, waist circumference	Total: 155	Total: 155	37.37 (12.60)	37.04 (12.07)	NR	71/84	72/83	25.35 (3.71)	26.28 (4.71)	NR	6	
Taneja et al. 2016[64]	India; NR	NR	Case-control study	Hcy	Total: 50	Total: 50	NR	NR	NR	NR	NR	NR	NR	NR	5	
Taneja et al. 2020[65]	India; NR	NR	Cross-sectional study	Hcy, TG, HDL, LDL, BMI, TC, waist circumference, smoking	Total: 54	Total: 54	32.4 (9.7)	30.7 (11.3)	10.3 (5.8)	22/33	19/35	24.0 (2.5)	23.9 (2.6)	NR	5	
Topal et al. 2016[66]	Turkey; NR	6/2013–5/2014	Descriptive research	Diabetes	NR	Total: 100	NR	NR	NR	NR	NR	NR	NR	NR	2	
Yasar et al. 2012[67]	Turkey; NR	NR	Case-control study	Hcy	Total: 40	Total: 40	25.42 (4.48)	27.77 (13.44)	NR	NR	NR	NR	NR	NR	6	
Jalel Akrem et al. 2008[68]	Tunisia; NR	9/2005–8/2006	Descriptive research	Diabetes	NR	Total: 60	NR	NR	NR	NR	NR	NR	NR	NR	4	
Zhang et al. 2009[69]	China; outpatient	12/2003–8/2007	Descriptive research	Diabetes	NR	Total: 6199	NR	24.5 (14.6)	NR	NR	3276/2923	NR	NR	NR	4	
Silverberg et al. 2013[70]	New York; NR	6/2010–7/2011	Descriptive research	Diabetes	NR	Total: 1541	NR	43.1 (13.4)	NR	NR	433/1080	NR	NR	NR	4	
Seung Kyung et al. 1993[71]	Korean; NR	3/1991–2/1993	Descriptive research	Diabetes	NR	Total: 226	NR	NR	NR	NR	103/123	NR	NR	NR	4	
Martis et al. 2002[72]	India; NR	NR	Descriptive research	Diabetes	NR	Total: 100	NR	NR	NR	NR	45/55	NR	NR	NR	4	
Kubeyinje et al. 1996[73]	Saudi Arabia; NR	5 years	Descriptive research	Diabetes	NR	Total: 167	NR	NR	NR	NR	NR	NR	NR	NR	5	
Korde et al. 2020[74]	India; NR	NR	Cross-sectional study	Diabetes	Total: 80	Total: 80	NR	NR	NR	NR	NR	NR	NR	NR	7	
Jacyk et al. 1976[75]	Poland; NR	NR	Descriptive research	Diabetes	NR	Total: 30	NR	NR	NR	NR	NR	NR	NR	NR	4	
Gill et al. 2014[76]	USA; NR	11 years	Descriptive research	Diabetes	NR	Total: 1098	NR	NR	NR	NR	593/505	NR	NR	NR	5	
Y. T. Chen et al. 2015[77]	Taiwan; NR	1997–2011	Cross-sectional study	Diabetes	Total: 59,532	Total: 14,883	NR	NR	NR	25564/33968	6391/8492	NR	NR	NR	8	
Dragoni et al. 2017[78]	Italy; NR	3/2012–3/2015	Case-control study	Smoking	Total: 200	Total: 200	NR	NR	NR	108/92	108/92	NR	NR	NR	8	
Balci et al. 2009[79]	Turkey; NR	NR	Case-control study	Hcy	Total: 31	Total: 48	39.32 (13.15)	37.94 (16.27)	9.28 (9.32)	14/17	27/21	NR	NR	NR	7	
Mustafa et al. 2023[80]	Egypt; NR	12/2021–6/2022	Case-control study	FBG, BMI, SBP, DBP, TC, TG, HDL, LDL, waist circumference, hyperlipidemia, Mts	Total: 100	Total: 100	36.4 (5.6)	32.7 (13.0)	5.9 (6.35)	35/65	30/70	NR	NR	NR	8	
EI-Hawary et al. 2022[81]	Egypt; outpatient	NR	Case-control study	BMI, waist circumference	Total: 70	Total: 70	15 (16.30)	22 (14.82)	24 (44.44)	24/46	27/43	24.59 (7.26)	21.49 (8.81)	NR	6	
Kalayci 2023[82]	Turkey; NR	1/2021–12/2021	Case-control study	CRP	Total: 78	Total: 78	35.8 (8.7)	33 (8.9)	NR	32/46	30/48	NR	NR	NR	7	
B. Li et al. 2023[83]	China; NA	1/2010–10/2021	A cross-sectional study	Smoking, alcohol	Total: 428	Total: 107	48.9 (11.4)	48.8 (11.4)	NR	256/172	64/43	NR	NR	NR	6	
Kassab et al. 2023[84]	Tunisia; NA	2020–2022	Case-control study	BMI	Total: 36	Total: 60	34.1 (13)	34.5 (10)	5.6 (4.3)	16/20	27/33	NR	NR	NR	5	
Ibrahim et al. 2022[85]	Egypt; NR	NR	Case-control study	SBP, DBP, TG, HDL, waist circumference, BMI, FPG, Insulin resistance	Total: 142	Total: 139	23 (17.78)	20 (17.04)	NR	55/87	51/88	NR	NR	NR	7	
Farajzadeh et al. 2022[86]	Iran; NR	4/2018–8/2020	Case-control study	Homocysteine	Total: 30	Total: 30	6.16 (2.98)	6.90 (3.74)	NR	15/15	14/16	NR	NR	NR	6	
Choudhary et al. 2022[87]	India; NR	NR	Case-control study	Homocysteine	Total: 30	Total: 70	NR	NR	NR	NR	NR	NR	NR	NR	6	
El-Hamd et al. 2023[88]	Egypt; outpatients	8/2020–8/2021	Case-control study	TC, TG, HDL, LDL, FPG, insulin, Insulin resistance, BMI	Total: 45	Total: 45	37.87 (13.99)	43.16 (14.76)	6.03 (8.67)	23/22	21/24	25.99 (3.93)	26.71 (3.33)	NR	7	
Abbreviations: Hcy, homocysteine; TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; BMI, body mass index; TG, triglycerides; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; CRP, C Reactive protein; Ph, phospholipids; Mts, metabolic syndrome; NR, not reported; VETI, vitiligo extent tensity index. A star scoring system was used to semiquantitatively assess study quality. In the selection and exposure categories, each numbered item was adjudged a maximum of four stars. A maximum of two stars was assigned for comparability. The NOS scores ranged from 0 to 9. We deemed studies achieving ≥7 stars as high-quality, those with 4–6 stars as medium-quality, and those with <4 stars as poor-quality.

Data extraction and quality assessment

Three reviewers independently extracted the data for each study using a predefined data extraction form. The extracted data included study design, number and characteristics of participants, indicators of inclusion, and disease duration. The Newcastle–Ottawa Scale was used to assess the study quality. Using this scale, case-control studies were categorized into selection, comparability, and exposure categories, whereas cohort studies were categorized into selection, comparability, and outcome categories. A maximum of one star can be awarded to each study for each item on the choice and exposure scales. Comparability can be awarded a maximum of two stars.

Data synthesis and analysis

The primary outcome was the comorbidity of metabolic syndrome, diabetes, hypertension, obesity, and hyperlipidemia in healthy controls and patients with vitiligo, and comorbidity rates were calculated accordingly. Simultaneously, the relationship between vitiligo and cardiovascular disease risk factors (such as hyperhomocysteinemia, HDL, and LDL) was analyzed. The I2 test was used to assess the degree of heterogeneity among studies. Considerable heterogeneity was identified for I2 values of > 50%. The global risk ratio (RR), standard error (SE), and mean difference (MD) were calculated using a random-effects model, and a sensitivity analysis was performed using the exclusion method. Fixed-effects models were used to examine studies with p > 0.05, I2 < 50%, or no significant within-study heterogeneity. A publication bias [14, 24, 26, 32,33, 41,42, 48, 63, 71, 77] analysis was performed for the primary outcome. The methods and results of this review followed the Epidemiological Group Guidelines, and the Checklists for Meta-Analysis of Observational Studies (Stata version 16.0; Stata Corp, College Station, TX, USA) were used for the meta-analysis.

Results

A total of 74 studies [13,14, 17–19, 21–79] involving 35362 participants with vitiligo were included. The details of the basic study characteristics are presented in Table 1. Based on the type of response variable, the meta-analysis consisted of two parts: The first part consisted of 46 studies [14, 19, 24–27, 31–34, 39, 41–43, 45,46, 48, 50,51, 54, 56, 58,59, 63, 65,66, 68–78, 80–88] with dichotomous metabolic syndrome, diabetes, obesity, hyperlipidemia, hypertension, smoking, and alcohol as response variables, and the second consisted of 36 studies [13, 17, 19, 21–23, 29–31, 35–39, 43,44, 47–49, 52–55, 57,58, 60–65, 67, 79, 83, 89] using continuous variables as response variables.

The main results showed that vitiligo had comorbidity with diabetes, obesity, hyperlipidemia, metabolic syndrome (Mts) and hypertension at rates of 6.0%, 38.5%, 43.0%, 28.3%, and 15.8%, respectively. The secondary outcomes indicated that the incidence of cardiovascular diseases in patients with vitiligo was associated with smoking, alcohol consumption, fasting blood glucose (FBG), insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), C-reactive protein (CRP), homeostasis model assessment of insulin resistance (HOMA-IR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and homocysteine (Hcy). In contrast, waist circumference, phospholipid levels, and body mass index (BMI) were not associated.

A publication bias analysis of the 11 papers was performed [14, 24, 26, 32,33, 41,42, 48, 63, 71, 77] with diabetes and vitiligo co-morbidities as the primary outcome. The analysis showed no bias, with Egger’s test coefficient = 0.651 (p = 0.301, which is >0.05) and Begg’s test p = 1.000, which is >0.05 (Table S1).

Primary outcomes

The comorbidity rates of patients with vitiligo were as follows: 28.3% of the patients had Mts [31, 39, 54, 58, 63, 80, 85](95% CI: 0.224, 0.345; p < 0.001; Table 2; Figure S21), 6.0% of the patients had diabetes [14, 24–27, 32–34, 41,42, 45,46, 48, 51, 56, 59, 63, 68–77] (95% CI: 0.041, 0.082; p < 0.001; Table 2; Figure S22), 38.5% were obese [26, 63], (95% CI: 0.089, 0.681; p = 0.011; Table 2; Figure S23), 15.8% had hypertension [5, 19, 25,26, 31, 63, 66], (95% CI: 0.061, 0.286; p = 0.001; Table 2; Figure S25), and 43.0% had hyperlipidemia [26, 31, 63, 80], (95% CI: 0.223, 0.650; p < 0.001; Table 2; Figure S24). Patients with vitiligo were more likely to have Mts [31, 39, 54, 58, 63, 80, 85] (RR: 1.894; 95% CI: 1.164–3.081; p < 0.05; Table 2; Figure S16), diabetes mellitus [14, 24, 26, 32,33, 41,42, 48, 63, 71, 77] (RR: 2.552; 95% CI: 1.990, 3.274; p < 0.001; Table 2; Figure S17), obesity [26, 63] (RR: 1.795; 95% CI: 1.168, 2.760; p = 0.008; Table 2; Figure S18), hyperlipidemia [26, 31, 63, 80] (RR: 1.380; 95% CI: 1.144, 1.664; p = 0.001; Table 2; Figure S19), and hypertension [19, 26, 31, 63] (RR: 1.330; 95% CI: 1.036, 1.707; p = 0.025; Table 2; Figure S20).

Table 2. Comorbidity and comorbidity rates of patients with vitiligo and metabolic syndrome, diabetes, obesity, hypertension, and hyperlipidemia.

Comorbidity	Number of studies	Vitiligo	Control	RR	95% CI	p value	I^2	
Events	Total	Events	Total	
Metabolic syndrome	7	203	704	113	696	1.894	[1.164, 3.081]	0.010	75.7%	
Diabetes	11	183	17,003	89	61,547	2.552	[1.990, 3.274]	0.000	7.6%	
Obesity	2	70	216	38	216	1.795	[1.168, 2.760]	0.008	39.7%	
Hyperlipidemia	4	175	379	111	381	1.582	[1.088, 2.302]	0.016	67.5%	
Hypertension	4	106	362	80	364	1.330	[1.036, 1.707]	0.025	9.3%	

Comorbidity rate	Number of studies	Events	Total	ES	95% CI	p value	I^2	
Metabolic syndrome	7	203	704	0.283	[0.224, 0.345]	0.000	67.5%	
Diabetes	27	443	32220	0.060	[0.041, 0.082]	0.000	97.4%	
Obesity	2	70	216	0.385	[0.089, 0.681]	0.011	94.3%	
Hyperlipidemia	4	175	379	0.430	[0.223, 0.650]	0.000	94.5%	
Hypertension	7	119	623	0.158	[0.061, 0.286]	0.001	93.3%	
CI, confidence interval; RR, risk ratio; ES, standard error.

Secondary outcomes

Diabetes

Eleven studies were included to evaluate FBG levels [19, 31, 36, 39, 48, 52, 54, 58, 63, 80, 85, 88] using a fixed-effects model, which showed that patients with vitiligo had significantly higher FBG levels than those of controls (MD: 0.389; 95% CI: 0.301, 0.477; p < 0.001; Table 3; Figure S1). In addition, a meta-analysis of five studies [36, 54, 61, 85, 88] showed a significant difference in the serum insulin levels between the vitiligo and control groups (MD: 0.653; 95% CI: 0.318, 0.988; p < 0.001; Table 3; Figure S2). Meanwhile, a significant effect on HOMA-IR was found between the vitiligo and control groups, which were modeled using the random effects from four of the eleven studies [36, 54, 85, 88] (MD: 0.674; 95% CI: 0.278, 1.070; p = 0.001; Table 3; Figure S3).

Table 3. Cardiovascular risk factors in patients with vitiligo.

Cardiovascular risk factors	Number of studies	N
(vitiligo)	N
(control)	MD	95% CI	p value	I^2	
Diabetes	 	 	 	 	 	 	 	
 FBG	12	1039	1005	0.389	[0.301, 0.477]	0.000	33.8%	
 Insulin	5	351	336	0.653	[0.318, 0.988]	0.000	75.2%	
 HOMA-IR	4	316	306	0.674	[0.278, 1.070]	0.001	80.4%	
Obesity	 	 	 	 	 	 	 	
 Waist circumference	12	1020	989	−0.014	[−0.233, 0.205]	0.900	83.1%	
 Non-segmental vitiligo	3	274	279	−0.118	[−1.031, 0.795]	0.800	95.9%	
 Segmental vitiligo	3	53	279	−0.792	[−1.675, −0.090]	0.079	83.6%	
 BMI	19	1313	1269	0.057	[−0.146, 0.260]	0.582	84.2%	
 Non-segmental vitiligo	3	274	279	−0.168	[−0.999, 0.662]	0.691	95.1%	
 Segmental vitiligo	3	53	279	−0.405	[−1.001, 0.190]	0.182	64.7%	
Hypertension	 	 	 	 	 	 	 	
 SBP	10	889	881	0.213	[0.023, 0.404]	0.028	74.5%	
 Non-segmental vitiligo	2	239	244	0.176	[−0.711, 1.062]	0.698	95.6%	
 Segmental vitiligo	2	18	244	0.132	[−0.347, 0.611]	0.590	8.9%	
 DBP	10	889	881	0.259	[0.062, 0.456]	0.010	76.0%	
 Non-segmental vitiligo	2	239	244	0.599	[0.417, 0.782]	0.000	0.0%	
 Segmental vitiligo	2	18	244	0.348	[−0.132, 0.828]	0.156	4.5%	
Hyperlipidemia	 	 	 	 	 	 	 	
 TC	12	681	682	0.665	[0.307, 1.022]	0.000	89.8%	
 TG	18	1987	1460	0.299	[0.140, 0.458]	0.000	76.9%	
 Non-segmental vitiligo	2	239	244	0.065	[−0.111, 0.241]	0.471	0.0%	
 Segmental vitiligo	2	18	244	−0.221	[−0.700, 0.257]	0.365	0.0%	
 LDL	13	766	757	0.594	[0.306, 0.882]	0.000	85.9%	
 HDL	18	1350	1333	−0.373	[−0.623, −0.123]	0.003	89.8%	
 Non-segmental vitiligo	2	239	244	0.174	[−0.215, 0.563]	0.380	77.5%	
 Segmental vitiligo	2	18	244	1.320	[−1.204, 3.843]	0.305	95.7%	
 Phospholipids	2	45	54	0.049	[−0.350, 0.448]	0.810	0.0%	
Other risk factors	 	 	 	 	 	 	 	
 Hcy	14	754	678	0.692	[0.352, 1.032]	0.000	89.3%	
 CRP	4	308	303	0.837	[0.320, 1.354]	0.002	87.5%	

Lifestyle	Number of studies	Vitiligo	Control	RR	95% CI	p value	I^2	
Events	Total	Events	Total	
Smoking	6	239	659	230	1000	1.376	[1.096, 1.726]	0.006	53.3%	
Alcohol	3	98	362	96	683	1.457	[1.127, 1.885]	0.004	0.0%	
CI, confidence interval; RR, risk ratio; Hcy, homocysteine; TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; BMI, body mass index; TG, triglycerides; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; CRP, C-reactive protein; Ph, phospholipids; HOMA-IR, homeostatic model assessment of insulin resistance.

Obesity

A meta-analysis of waist circumference [17, 19, 31, 47, 52, 54, 58, 63, 65, 80,81, 85] of patients with vitiligo and controls revealed high heterogeneity (I2 = 83.1%, p < 0.001). We observed no significant difference between the waist circumferences of patients with vitiligo and those of controls in twelve studies, with a pooled MD of −0.014 (95% CI: −0.233, 0.205, p = 0.900; Table 3; Figure S4) using a random-effects model. Three of these studies [54, 63, 81] showed no difference between the waist circumferences of the patients with nonsegmental vitiligo and those of the controls (MD: −0.118; 95% CI: −1.031, 0.795; p = 0.800; Table 3; Figure S4) and, similarly, no difference between the waist circumferences of patients with segmental vitiligo and those of controls (MD: −0.792; 95% CI: −1.675, −0.090; p = 0.079; Table 3; Figure S4).

A meta-analysis of 19 studies [19, 29, 36,37, 39, 43, 47, 52–54, 58, 63, 65, 77, 80,81, 84,85, 88] showed no significant difference in the BMI between patients with vitiligo and the controls (MD: 0.057;95% CI: −0.146, 0.260; p = 0.582; Table 3; Figure S5), two studies [54, 63] reflected no significant difference in the BMI between patients with segmental (MD: −0.385;95% CI: −1.553, 0.783; p = 0.518; Table 3; Figure S5) and non-segmental vitiligo (MD: −0.133;95% CI: −1.327, 1.062; p = 0.828; Table 3; Figure S5) and the controls.

Hypertension

Ten studies [19, 29, 31, 39, 52, 54, 58, 63, 80, 85] analyzed the SBP and DBP of patients with vitiligo and the control groups; the meta-analysis showed a significant difference in the SBP (MD: 0.213; 95% CI: 0.023, 0.404; p = 0.028; Table 3; Figure S6) and DBP (MD: 0.259; 95% CI: 0.062, 0.456; p = 0.05510; Table 3; Figure S7); the meta-analysis of two of the studies [54, 63] indicated no significant difference in the SBP between patients with non-segmental (MD: 0.176; 95% CI: −0.711, 1.062; p = 0.698; Table 3; Figure S6) and segmental vitiligo (MD: 0.132; 95% CI: −0.347, 0.611; p = 0.590; Table 3; Figure S6) and the controls, and no significant difference in DBP was observed between patients with segmental vitiligo (MD: 0.348; 95% CI: −0.132, 0.828; p = 0.156; Table 3; Figure S7) and the controls. However, significant differences in DBP were noted between patients with nonsegmental vitiligo (MD: 0.599; 95% CI, 0.417–0.782; p < 0.001; Table 3; Figure S7) and the controls.

Hyperlipidemia

Twelve studies [13, 19, 23, 29, 37, 39, 47, 52,53, 65, 80, 88] compared serum TC levels between patients with vitiligo and controls; the meta-analysis revealed that serum TC levels were significantly higher in patients with vitiligo than in the controls (MD: 0.665; 95% CI: 0.307, 1.022; p < 0.001; Table 3; Figure S8).

A meta-analysis of 18 studies [13, 19, 22,23, 29, 31, 36, 39, 52–54, 58, 60, 63, 65, 80, 85, 88] indicated that the serum TG levels of patients with vitiligo were significantly higher than those of the controls (MD: 0.299; 95% CI: 0.140, 0.458; p < 0.001; Table 3; Figure S9). Two studies [54, 63] analyzed the serum TG levels of patients with segmental and nonsegmental vitiligo and controls. The results of the meta-analysis showed no significant difference in the serum TG levels between patients with segmental vitiligo and the controls (MD: −0.221; 95% CI: −0.700, 0.257; p = 0.365; Table 3; Figure S9). Moreover, the serum TG levels of the patients with non-segmental vitiligo were not significantly different from those of the control group (MD: 0.065; 95% CI: −0.111, 0.241; p = 0.471; Table 3; Figure S9).

A meta-analysis of 13 studies [13, 19, 23, 29, 36, 39, 47, 52,53, 63, 65, 80, 88] showed that the serum LDL levels of patients with vitiligo were significantly higher than those of the controls (MD: 0.594; 95% CI: 0.306–0.882; p < 0.001; Table 3; Figure S10). A meta-analysis of 18 studies [13, 19, 21, 23, 29, 31, 36, 39, 47, 52–54, 58, 63, 65, 80, 85, 88] showed that patients with vitiligo had lower serum HDL levels than those of the controls (MD: −0.373; 95% CI: −0.623, −0.123; p = 0.003; Table 3; Figure S11). A meta-analysis of two of these studies [54, 63] showed that the serum HDL levels of patients with segmental (MD: 1.320; 95% CI: −1.204, 3.843; p = 0.305; Table 3; Figure S11) and non-segmental (MD: 0.174; 95% CI: −0.215, 0.563; p = 0.380; Table 3; Figure S11) vitiligo were not significantly different from those of the controls.

A meta-analysis of two studies [23, 53] showed no significant difference in serum phospholipid levels between patients with vitiligo and the controls (MD: 0.049; 95% CI: −0.350, 0.448; p = 0.810; Table 3; Figure S26).

Lifestyle

Six studies [43, 58, 63, 65, 78, 83] compared the smoking habits of patients with vitiligo and control groups. The results of the meta-analysis indicated that the number of smokers in the vitiligo group was higher than that in the controls (RR: 1.376; 95% CI: 1.096, 1.726; p = 0.006; Table 3; Figure S14).

Simultaneously, we conducted a meta-analysis of three studies [54, 63, 83], which indicated that the number of vitiligo patients with alcohol addiction was significantly higher than that of the controls. (RR: 1.457; 95% CI: 1.127, 1.885; p = 0.004; Table 3; Figure S15).

Other risk factors

A meta-analysis of 14 studies [30, 35, 38, 44, 49, 55, 57, 62, 64,65, 67, 79, 86,87] analyzing the serum Hcy levels of patients with vitiligo and controls indicated that patients with vitiligo had significantly higher serum Hcy levels than those of the controls (MD: 0.692; 95% CI: 0.352, 1.032; p < 0.001; Table 3; Figure S12).

A meta-analysis of four studies [29, 52, 63, 82] showed that the serum CRP levels of patients with vitiligo were significantly higher than those of the controls (MD: 0.837; 95% CI: 0.320, 1.354; p = 0.002; Table 3; Figure S13).

Discussion

Vitiligo is a skin disease affecting people worldwide. Its pathogenesis is unclear; however, it is believed to be related to several factors, such as heredity, immunity, and oxidative stress [9–11]. Previous studies have reported a relationship between vitiligo and cardiovascular diseases [16–18]. In contrast, a case-control study conducted in Spain provided conflicting results [20]. Therefore, since the relationship between vitiligo and cardiovascular diseases is unclear and controversial among clinicians, a meta-analysis is needed to examine the association between vitiligo and cardiovascular diseases.

Few articles have described the direct relationship between vitiligo and cardiovascular diseases (such as acute coronary syndrome and coronary heart disease). Therefore, this meta-analysis focused on the risk factors for cardiovascular diseases in patients with vitiligo. Cardiovascular disease accounts for approximately one-third of all deaths worldwide, and its prevalence continues to increase as the population ages [90]. It is a disease with multiple contributing factors; therefore, it is difficult to identify the specific factors in isolation. The main factors associated with the present study were obesity, dyslipidemia, high blood pressure, lifestyle (drinking and smoking), Hcy and CRP levels, and hyperglycemia [91,92].

Previous studies have reported a correlation between vitiligo and its common comorbid atopic and autoimmune diseases, such as diabetes, autoimmune thyroid diseases, psoriasis, pernicious anemia, Addison’s disease, and systemic lupus erythematosus [12–14, 23–27, 32–34, 40–42, 45,46, 51, 56, 59, 63, 66, 68–77]. In addition, our study showed that the comorbidities of vitiligo include diabetes, which is consistent with previous findings.

As expected, patients with vitiligo are at an increased risk of metabolic syndrome [17,18, 22, 29, 31, 39, 52, 54,55, 58, 60, 63], and significant differences were observed in the prevalence of metabolic syndrome between patients with vitiligo and the controls. We did not observe any significant differences in the waist circumference or BMI between the vitiligo and control groups. The results of a meta-analysis conducted in 2022 in China [89] and a case-control study in Africa [54] were contrary to our results; however, those of another meta-analysis conducted in 2022 in Taiwan and China [93] and three case-control studies in Asia [31, 39, 58, 63] were consistent with our results. Differences in ethnicity may be responsible for this discrepancy in metabolic syndrome. It has also been suggested that vitiligo and insulin resistance are components of metabolic syndrome [94]. Waist circumference and BMI did not significantly differ in patients with vitiligo compared to those in controls; therefore, obesity cannot be considered a risk factor for cardiovascular disease in patients with vitiligo. Given that the prevalence of obesity in patients with vitiligo is approximately 38.5%, dermatologists and other physicians are advised to be vigilant in clinical situations. Hypertension is the most common potential risk factor for cardiovascular disease [95], and this study showed that patients with vitiligo have significantly higher SBP and DBP than controls.

TC, TG, HDL, LDL, FBG, and insulin levels are considered uncontroversial risk factors for cardiovascular disease. The TC level does not exactly reflect that of HDL and LDL cholesterol and therefore cannot be used as a separate indicator of the magnitude of the risk of atherosclerosis. The contribution of TG to cardiovascular disease may lead to low-grade inflammation, foam cell formation, and atherosclerotic plaque formation [96–99]. HDL has the ability to promote reverse cholesterol transport and protect LDL from oxidative modifications. The lysolemic lipid sphingosine-1-phosphate (S1P), present in HDL, can promote vasodilation and angiogenesis and prevent ischemia/reperfusion injury, and the expression of anti-inflammatory cytokines can be induced by HDL. These antioxidant and anti-inflammatory properties of HDL can antagonize the inflammatory process underlying atherosclerosis [100–104]. LDL transports cholesterol to peripheral tissues and, together with very-low-density lipoprotein and celiac remnant particles, accumulates in dysfunctional subendothelial vessel walls. Oxidative stress induces the oxidative modification of LDL particles and accumulation of oxidized LDL in macrophages, triggering a pro-inflammatory macrophage response, excessive macrophage apoptosis, and endothelial cell activation, leading to persistent vascular inflammation in atherosclerotic lesions [105–107]. Hyperglycemia can promote vascular complications through multiple mechanisms, such as the formation of late glycation end-products, and increased oxidative stress can lead to macrovascular and microvascular complications. Myocardial microangiopathy can lead to scattered myocardial fibrosis and necrosis. Studies have shown that FBG levels contributes to subclinical myocardial injuries. In addition, a sustained but mild inflammatory response induced by hyperglycemia leads to further enhancement of oxidative stress and further release of inflammatory factors, and both inflammation-induced microvascular and macrovascular disease can further increase high-sensitivity cardiac troponin T levels, leading to subclinical myocardial injury [108,109]. A hyperinsulinemia environment leads to insulin resistance; however, the additional cellular response to high insulin levels is not attenuated by insulin resistance. Hyperinsulinemia and insulin resistance trigger cardiovascular disease by inducing endothelial dysfunction, inhibiting endothelial nitric oxide synthase, and activating and promoting calcium ion influx into smooth muscle cells, thereby enhancing vascular tone and renal tubular reabsorption of sodium ions, causing macrophages to adhere to the vessel wall and forming arterial lesions [110]. Furthermore, our study overturned the findings of previous studies and showed significant differences in the TC, TG, HDL, LDL, FBG, HOMA-IR and insulin levels between patients with vitiligo and the controls.

Hcy and CRP are independent risk factors for high cardiovascular disease risk [111–115]. Previous studies have shown that Hcy is involved in the pathogenesis of atherosclerosis by stimulating CRP production and triggering inflammatory responses in vascular smooth muscle cells [116]. CRP is present in most atherosclerotic plaques and all acute myocardial infarction lesions and accumulates during the development of atherosclerosis. Endothelial nitric oxide production is inhibited by CRP, the expression of endothelial cell adhesion molecules is promoted by CRP, monocyte recruitment to atheromatous plaques is facilitated, and modified LDL leads to plaque instability. Platelet activation and thrombus growth are also induced by CRP [117,118]. We found that the serum CRP levels in patients with vitiligo were higher than those in the control group, thus providing a basis for the relationship between vitiligo and cardiovascular diseases. However, conflicting reports on the correlation between vitiligo and serum Hcy levels exist [55]. Our study demonstrated that serum Hcy levels were significantly higher in patients with vitiligo than in the controls, suggesting the clinical significance of serum Hcy levels in preventing cardiovascular events in patients with vitiligo. Unfortunately, our study lacked the data to clarify the relationship between vitiligo and serum homocysteine levels.

The role of lifestyle in the relationship between vitiligo and cardiovascular disease is intriguing. Here, we discuss only smoking and drinking habits. Smoking is a risk factor for cardiovascular disease. The key processes of smoking-induced atherosclerosis are endothelial dysfunction and damage, resulting in increased and oxidized atherogenic lipids and decreased HDL levels, inducing inflammation and contributing to a pro-coagulant state in the circulation [119,120]. Enomoto et al. [121] demonstrated that smoking is a risk factor for vitiligo on the hands, and fingertip vitiligo may be associated with direct exposure to cigarette smoke. However, the relationship between alcohol consumption and cardiovascular disease remains complex and controversial [122,123].

Interestingly, a recent cohort study showed that both light and heavy alcohol consumption is associated with an increased risk of cardiovascular disease [124,125]. However, the underlying mechanism remains unclear and may be associated with an increased risk of hypertension associated with alcohol consumption. Our research showed that the number of smokers and alcoholics among patients with vitiligo was significantly higher than in the control group. Therefore, clinicians should consider in the lifestyles of patients with vitiligo. Future studies should explore the relationship between alcohol consumption and vitiligo and the relationship between alcohol consumption and cardiovascular diseases in patients with vitiligo.

Limitations

This study had several limitations. First, data on cardiovascular disease risk factors in patients with segmental and non-segmental vitiligo are sparse, and the evidence is insufficient. Second, this study was highly heterogeneous, which may be due to the different regimens, doses, durations, center settings, and population registries. Third, most studies were conducted in Eastern countries; therefore, the extrapolation of these results to Western populations is questionable. Fourth, several studies had a serious source of bias. Fifth, the effect in many occasions was assessed by very few studies; thus, the evidence to support this finding is low.

Conclusions

Our study identified cardiovascular disease risk factors in patients with vitiligo, including smoking; alcohol consumption; high serum FBG, CRP, TC, TG, LDL, insulin, and Hcy levels; and low serum HDL levels (Figure 2). Cardiovascular risk factors in patients with vitiligo were not associated with BMI, waist circumference, systolic and diastolic blood pressure, or phospholipid levels. Moreover, patients with vitiligo are prone to complications, such as diabetes, obesity, hyperlipidemia, and hypertension. Therefore, although an inevitable relationship exists between vitiligo and cardiovascular diseases, further research is required to evaluate the causal relationship between them and to identify the cardiovascular diseases more closely related to vitiligo.

Supplementary Material

Supplemental Material

Authors’ contributions

Xin Liang contributed to data curation, methodology, writing of the original draft, and revision of the paper for important intellectual content. Fei Guo contributed to data curation, methodology, writing of the original draft, and revision of the paper for important intellectual content. Miao Zhang contributed to data curation and revision of the manuscript for important intellectual content. Chunxiao Wang contributed to data analysis and revision of the paper for important intellectual content. Naixuan Lin contributed to the validation and revision of the paper for important intellectual content. Li Liu contributed to the investigation and revision of the paper for important intellectual content. Yan Chen contributed to resources and revision of the paper for important intellectual content. Fang Liu contributed to data analysis, drafting of the paper, and revision of the paper for important intellectual content. Yuhua Du contributed to the visualization and revision of the manuscript for important intellectual content. Lei Li contributed to the conception and design of the study and approved the final version to be published. Xin Li contributed to the conceptualization, methodology, writing, reviewing, editing, and revision of the paper for important intellectual content. All authors approved the final manuscript.

Disclosure statement

The authors declare no conflict of interest regarding the publication of this paper.

Data availability statement

All data generated or analyzed during this study are included in this published article (and its Supplementary Information Files).
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