Heilongjiang Province is located in the northernmost part of China, and we conducted this relatively large-sample retrospective study in this high-latitude region. Psoriasis is a systemic inflammatory disease that involves more than just the skin. In our study, the prevalence of combined psoriasis with a history of CVD was roughly 1.52 times higher than that in the control group, and the prevalence of combined hypertension, diabetes, obesity, and conventional dyslipidaemia were also higher than those in the control group, which is generally consistent with previous studies on psoriatic comorbidities [7, 13, 19]. Furthermore, our study showed that a combined history of CVD was approximately 1.72 times higher in patients with psoriasis > 10 years than in those with psoriasis ≤ 10 years, implying that the longer the duration of psoriasis, the more likely it is to be comorbid with CVD. In the natural population, it is also the case that the older the patient, the more likely they are to develop CVD, a confounding factor caused by the natural aging process. It is important to note that a longer disease duration is not associated with older age, and in our study, a significant number of patients had psoriasis from a young age, and developed CVD or associated risk factors at a relatively younger age.
Yamazaki et al. found that, in Japan, patients with more severe psoriasis did not necessarily exhibit a higher proportion of CVD risk as PASI scores increased [36], which is similar to our results, where patients with more severe psoriasis in the North did not exhibit a higher proportion of CVD risk (Fig. 2). However, we found that psoriasis patients with a PASI > 10 points were roughly twice as likely to have comorbid diabetes as psoriasis patients with a PASI ≤ 10 points. Armstrong et al. found that patients with both diabetes and psoriasis were at a greater risk of microvascular and macrovascular complications than those without psoriasis [4]. The inflammatory factors TNF-α and IL-6 have been reported to promote insulin resistance [11], and cardiometabolic disease is prevalent among patients with psoriasis, especially in those with more severe skin disease, which may be an independent risk factor for diabetes and major adverse cardiovascular events (MACE) [22].
The core pathogenesis of psoriasis involves IL-17 and IL-23, which are key adaptive immune pathways, and TNF-α is an upstream factor in this pathway, which can induce the expression of IL-17 and amplify the expression of other cytokines [8]. Numerous studies have shown a significant correlation between psoriasis and hypertension prevalence, where hypertension is more prevalent in patients with psoriasis than in those without [5, 12]. A meta-analysis of 24 observational studies was conducted, which showed that patients with psoriasis with hypertension had more severe hypertension and poorly controlled blood pressure than patients without psoriasis [3, 31]. In our study, the incidence of hypertension in psoriasis patients was roughly 1.52 times higher than that in the control group. Studies have demonstrated in both human and mouse models that hypertension severity correlates with levels of IL-17a, which has been identified as a key mediator in experimental hypertrophic angiotensin II infusion models [25]. Studies have confirmed that murine overproduction of IL-17a promotes hypertension and left ventricular hypertrophy, while treatment with IL-17a inhibitors alleviates this phenotype, thus highlighting IL-17a as a contributing factor to hypertension in psoriasis [20, 28].
Obesity is an independent risk factor of psoriasis [18]. In studies on incidental psoriasis, the risk of psoriasis was found to increase with higher BMI [27]. Our findings show that for every one-unit increase in BMI, the associated risk of comorbid psoriasis increases approximately 0.06-fold, while for obese people with psoriasis, weight loss can improve their psoriatic skin condition. Langan et al. performed a cross-sectional study of patients with psoriasis in the United Kingdom for whom information on body surface area (BSA) involvement in psoriasis was available and found a positive dose-dependent relationship between objective measures of psoriasis severity and obesity [22]. Disrupted adipokine production in adipose tissue of obese patients with psoriasis may lead to chronic skin and systemic inflammation and increased cardiovascular risk. TNF-α is an important factor located upstream of the inflammatory pathway in psoriasis. Weight loss has also been shown to improve the efficacy of anti-TNF-α biological therapy in obese patients with psoriasis [2].
It is well known that HDL and Apo A levels in blood lipids are negatively correlated with the incidence of coronary heart disease and are more sensitive indicators for the diagnosis of coronary heart disease. TG and Lp (a) are risk factors for atherosclerosis and are positively correlated with many cardiovascular diseases. In our study, approximately 41.71% of the patients had psoriasis accompanied by lower HDL levels. Advanced lipid testing techniques have demonstrated a more atherogenic lipid profile and decreased high-density lipoprotein cholesterol efflux capacity in patients with and without psoriasis [16, 24]. Furthermore, high-density lipoprotein cholesterol efflux capacity is directly related to the coronary artery disease burden in patients with psoriasis and is suggested to be an important proxy for CVD [30]. Plasma HDL levels are particularly low in patients with a longer disease duration throughout the course of psoriasis. In addition, higher TG (15.46%) and Lp (a) (16.59%), and lower Apo A (61.48%) were also statistically significant indicators, which may be important causes of CVD in patients with psoriasis. Studies have shown that high titres of autoantibodies against HDL and Apo A are present in chronic inflammatory diseases, which are associated with high cardiovascular risk, and these antibodies are also found in patients with psoriasis and are associated with disease severity [9].
Numerous epidemiological studies have suggested psoriasis to be an independent risk factor for MI, stroke, and death due to CVD, collectively termed MACE, which may be based on shared inflammatory and pathophysiological pathways between psoriasis and CVD, including cytokine TNF-α that amplifies chronic type 1 helper (Th1) T-cell responses [23] and Th17-mediated inflammation [34], and neutrophils that induce endothelial cell damage [32], and increase oxidative stress [6], uric acid [21], vascular inflammation [33], and circulating microparticles [29], which may explain the increased CVD risk associated with psoriasis. Additionally, persistent pathophysiological processes that drive psoriasis, such as endothelial dysfunction, activated platelets, and dyslipidaemia, may also have multiple adverse effects on the cardiovascular system, leading to atherosclerosis [35].
For a long time, the FRS has been widely used as a traditional tool in cardiovascular medicine, and the effective assessment of 10-year CVD risk is a core component of primary CVD prevention [1]. Our results showed that the proportion of the psoriasis group in the "medium risk" and "very high risk" for CVD was significantly higher than that in the control group. In predicting heart age, the number of people whose predicted age was higher than their actual age was significantly increased in the "old people" group, their heart age was often greater than their actual age, and the aging of their heart may be accelerated. CVD can directly affect the overall health and life expectancy of psoriasis patients. For psoriasis patients without CVD manifestations at the time of consultation, preliminary prediction of the patient's future CVD risk possibility can enable doctors to guide them to actively prevent CVD, which has practical clinical significance, and could enable patients to have a deeper understanding of their own disease.