Prediction of cardiovascular disease risk in patients with psoriasis in northern China

Abstract

To investigate cardio vascular disease (CVD) risk factors and predict future CVD risk in patients with psoriasis in northern China, we conducted a retrospective study on risk factors in 1,067 psoriasis patients (psoriasis group) and 1,110 physical examiners without psoriasis (control group). Compared with the control group, the psoriasis group showed a stronger correlation with CVD history, body mass index, hypertension, diabetes mellitus, and dyslipidaemia (all P < 0.01). CVD was more common in patients with a long history of psoriasis (P < 0.01), and the incidence of severe psoriasis with diabetes was higher (P < 0.01). In the psoriasis prediction group, the proportion in psoriasis in the "medium risk" and "very high risk" was significantly higher (P < 0.01). Heart age was significantly increased than their actual in the "old people" (P < 0.01). The results showed that the risk factors for CVD in patients with psoriasis were higher than those in the control group, and psoriasis with a long history or severe disease had a higher risk of CVD. Patients with psoriasis have a higher risk of future CVD, and the predicted heart age in the older groups tends to exceed the actual age. This suggests that attention should be paid to the present and future risk of CVD in patients with psoriasis and to the management of cardiovascular comorbidities.

Introduction

Approximately 125 million people worldwide suffer from psoriasis, with a prevalence of 0.48% in China¹. In 2006, Gelfand et al. were the first to consider psoriasis as an independent risk factor for the exacerbation of cardiovascular risk². A meta-analysis of 75 studies showed that patients with psoriasis had a 50% increased risk of CVD compared with patients without psoriasis³. Several studies have shown that the key inflammatory factors responsible for psoriasis, such as tumour necrosis factor (TNF-α) and interleukin 17 (IL-17), act not only on the skin but also throughout the body, and that synergistic components of IFN-γ, TNFα, and IL-17 family cytokines play a leading role in endothelial dysfunction and the development of atherosclerosis^4,5. This study of psoriasis in combination with cardiovascular comorbidities is gaining attention from physicians and patients, and it is particularly important to predict the cardiovascular risk associated with psoriasis in patients without comorbid manifestations.

Heilongjiang Province is located in the northernmost part of China and is characterized by cold and weak ultraviolet rays, making it a high-incidence area for psoriasis and CVD. However, in this high-latitude region, there is a paucity of information on the relationship between psoriasis and CVD, and there are no studies on the predictors of future CVD risk in patients with psoriasis. The Framingham Risk Score (FRS)⁶ is one of the most widely used methods for predicting the risk of CVD over the next 10 years. In this study, we compared CVD risk factors and predict the individual 10-year risk of CVD and heart age in patients with psoriasis in the northern China region.

Materials And Methods

Study Participants

This was a retrospective study with data from the largest comprehensive dermatology treatment centre in Heilongjiang Province, with the majority of patients coming from Heilongjiang Province or the surrounding provinces. The study population was divided into a psoriasis group and a control group, in which the psoriasis group consisted of 1,067 patients with psoriasis who were first admitted to the Department of Dermatology of the First Affiliated Hospital of Harbin Medical University from 1 January 2014 to 31 June 2021, and the control group consisted of 1,110 physical examiners in the same period. All data for this study were obtained from the electronic medical records and database registry of the First Affiliated Hospital of the Harbin Medical University. All procedures were approved by the Ethics Committee of the First Affiliated Hospital of Harbin Medical University, No. IRB-AF /SC-04/01.0, and informed consent was waived due to the retrospective nature of the study.Research involving human research participants have been performed in accordance with the Declaration of Helsinki. we confirming that all experiments were performed in accordance with relevant guidelines and regulations.

Inclusion criteria

We included patients aged ≥ 16 years with psoriasis and controls, diagnosed according to internationally recognised International Classification of Disease (ICD) codes. For data accuracy, we established the following exclusion criteria: (1) incomplete medical records; (2) familial hyperlipidaemia, familial hypertension, type I diabetes mellitus, and severe endocrine system disorders; (3) use of medication affecting lipids within three months; and (4) those with repeated multiple hospitalisations or duplicate medical records. 

Definition and collection of data

This study defines dyslipidaemia in the traditional sense⁷, referring to patients with high total cholesterol (TC)), high triglycerides (TG), and low high-density lipoprotein (HDL). In a broader sense, dyslipidaemia also typically includes abnormalities in low-density lipoprotein (LDL), Apolipoprotein (Apo) A, Apo B, and lipoprotein (Lp) (a). Among all the blood lipid indices, the abnormality of Apo A and HDL was lower than the normal value, and the abnormality of the remaining values was higher than the normal value. The normal value range based on hospital laboratory department’s regulation: TC: 3.35 mmol/L~5.71 mmol/L; TG:0.48 mmol/L~2.25 mmol/L; HDL1.03 mmol/L~1.55 mmol/L; LDL0.26 mmol/L ~ 4.11 mmol/L; Apo A 1.2 g/L~1.6 g/L; Apo B 0.8 g/L~1.05 g/L; L p(a) 0.01~400 mg/L.

A history of smoking was defined as an average of >20 cigarettes per day for smokers, and a history of alcoholism was defined as an average of >200 g of alcohol per day for drinkers. As defined by the FRS score, CVD history in this study was defined as having any of the following: coronary atherosclerosis, myocardial infarction (MI), coronary artery supply deficiency, angina pectoris, ischemic stroke, haemorrhagic stroke, transient ischemic attack, peripheral arterial disease, and heart failure.

The data collected included the following: (1) General characteristics: sex, age, and body mass index (BMI). (2) Psoriasis-related data: psoriasis area and severity index (PASI) and course of psoriasis. (3) CVD-related risk factors: history of CVD, smoking, alcoholism, hypertension, systolic blood pressure, diabetes, and lipid indicators. The lipid indicators collected included TC, TG, HDL, Apo A, Apo B, LDL, and Lp (a).

Study design

To investigate CVD risk factors, a retrospective study was conducted on the following groups:(1) 1,067 patients with psoriasis (psoriasis group) and 1,110 physical examiners without psoriasis (control group). (2) In the psoriasis group, according to the course of disease ≤10 years (n=682) and >10 years (n=385); and (3) according to the severity of PASI≤10 (n = 372) and PASI > 10 (n = 695).

To compare CVD risk predictors, patients with psoriasis who had no history of CVD and were older than 30 years were extracted from the psoriasis group and referred to as the "psoriasis prediction group” (n = 705). These patients were compared with 768 matched controls, where the FRS score was used to calculate the CVD risk score for the next 10 years and the predicted cardiac age of the participants⁶. 

FRS score

The "General CVD Risk Prediction" model (see Appendix 1) is derived from the Framingham Cardiovascular Institute⁶ and is based on eight factors: sex, age, total cholesterol, HDL, systolic blood pressure level, treatment of hypertension (yes/no), smoking status, and history of diabetes. To perform CVD risk assessment and stratification, patients were classified by the FRS score into five risk categories: very low risk group (< 1 point), low risk (1–6 points), medium risk (6–20 points), high risk (20–30 points), and very high risk (>30 points).Patients are divided into four categories according to World Health Organization's age regulations: youth group (18–44 years), middle aged group (45–59 years),the young old group (60–74 years), and old people (>75 points years).

Statistics

All statistical analysis was performed using SPSS 25.0 software. Categorical variables were compared using the chi-square test, continuous variables that conformed to a normal distribution were compared using t-tests, continuous variables that did not conform to a normal distribution were compared using Mann–Whitney U-tests, and multi-factor logistic regression was used to calculate the odds ratio (OR), p < 0.05 was considered to be statistically significant.

Results

The psoriasis and control groups were matched in advance according to age, sex, smoking status, and alcohol status (p > 0.05). The general clinical characteristics of the two groups are compared in Table 1. Multi-factor logistic regression analysis included all data, and Table 1 shows that the proportion of patients with psoriasis that had a combined history of CVD was higher (OR: 1.52, 95% confidence interval [CI]: 1.16–1.99) and the following CVD risk factors were associated with psoriasis: BMI (OR: 1.06, 95% CI: 1.04–1.08), where the proportion of people who were overweight (BMI ≥ 24) and obese (BMI ≥ 28) were significantly higher (p < 0.01), hypertension (OR: 1.52, 95% CI: 1.24–1.86), diabetes (OR. 1.45, 95% CI: 1.07–1.97), and dyslipidaemia (OR: 2.74, 95% CI: 2.28–3.27), and were statistically significant (p < 0.01).

In comparing the two groups of people with abnormal lipid values, the psoriasis patients had significantly higher TG and Lp (a) levels, and significantly lower HDL and Apo A levels than the control group, which were all statistically significant (p < 0.01) (Table 2). There were no significant differences in TC, LDL, or Apo B levels between the two groups.

Table 3 shows, in terms of dyslipidaemia, that the psoriasis group had a higher and statistically significant proportion of people with higher TG, TC, and Lp (a), and lower HDL and Apo A (all p < 0.05). In the comparison of the proportion of people with abnormal LDL and Apo B, there was no significant difference between the two groups.

The psoriasis group was sub-grouped according to the psoriasis course. Figure 1 shows that patients with psoriasis for > 10 years (n = 385, 36.08%) were more likely to have combined CVD than those with psoriasis for ≤ 10 years (n = 682 patients, 63.92%) (p < 0.01, OR: 1.72, 95% CI: 1.22–2.42). All other CVD risk factors did not show a significant correlation with disease duration.

The psoriasis subgroups were grouped according to PASI and statistically analysed using a multi-factor logistic regression analysis. Figure 2 shows that severe psoriasis with a PASI > 10 points (n = 695 cases, 65.14%) was significantly associated with diabetes (p < 0.01, OR: 2.00, 95% CI: 1.37–2.93), while the remaining CVD risk factors were not significantly correlated with severity.

In the psoriasis group, 705 individuals aged > 30 years with no history of CVD were extracted for the FRS score, and referred to as “psoriasis predictor group". The control group was matched according to sex, age, smoking status, and alcohol consumption (p > 0.05).

In comparing the two groups (Fig. 3), the proportion of people in the "medium risk" and "very high risk" groups were significantly higher in the psoriasis predictor group than in the control group (p < 0.05), and the proportion of people in the "very low risk" group in the psoriasis predictor group was significantly lower than that in the control group (p < 0.01).

The model provided by the FRS score predicted cardiac age in the "psoriasis predictor group", the statistically significant result only in "the old people group ": the number of people whose predicted cardiac age was higher than their actual cardiac age increased significantly (p < 0.01) (Fig. 4).

Discussion

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^8–10. 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 increased¹¹, 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 psoriasis¹². The inflammatory factors TNF-α and IL-6 have been reported to promote insulin resistance¹³, 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)¹⁴.

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 cytokines¹⁵. 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^16,17. 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^18,19. 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 models²⁰. 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^21,22.

Obesity is an independent risk factor of psoriasis²³. In studies on incidental psoriasis, the risk of psoriasis was found to increase with higher BMI²⁴. 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 obesity¹⁴. 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 psoriasis²⁵.

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^26,27. 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 CVD²⁸. 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 severity²⁹.

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 responses⁵ and Th17-mediated inflammation³⁰, and neutrophils that induce endothelial cell damage³¹, and increase oxidative stress³², uric acid³³, vascular inflammation³⁴, and circulating microparticles³⁵, 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 atherosclerosis³⁶.

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 prevention³⁷. 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.

Declarations

Acknowledgements

This study was supported by the Natural Science Foundation of Heilongjiang Province (LH2021H054).

Author contributions

Feng Zhang, as the corresponding author, introduced the concept and design of the study. Qian Fu was responsible for manuscript preparation and statistical analysis as the first author. Dongqiang Su is responsible for manuscript editing and literature retrieval as a co-author. Yu Miao was responsible for literature retrieval as the second author, and Taoyu Chen and Yanqi  Ji were responsible for data analysis and data collection as the third and fourth authors, respectively. Zhang Feng, as the corresponding author, is responsible for the integrity of the entire process from inception to publication. All authors reviewed the manuscript.

Data availability statement

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Additional Information 

Competing Interests Statement

The authors declare no conflicts of interest.

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