Correction: Association between systemic inflammation indicators and psoriasis: a cross-sectional study from NHANES
Year: 2025
Type: erratum
Abstract: 1. Introduction Psoriasis is a complex and multifaceted chronic inflammatory skin disorder that affects a substantial portion of the global population. The characteristic scaly plaques not only cause physical discomfort but also impose a substantial burden on individuals and society at large. This disease is frequently associated with numerous comorbidities, including psoriatic arthritis, cardiovascular problems, metabolic syndrome, obesity, gastrointestinal disorders such as inflammatory bowel disease, and mental health disorders[1]. The immune system plays a crucial role in both the initiation and progression of psoriasis. In particular, Th17 cells and dendritic cells (DCs) are central to the dysregulated inflammatory response. These cells, along with other immune components such as mast cells, monocytes, neutrophils, innate lymphoid cells (ILCs), and macrophages, form an interconnected network that collaboratively drives the chronic inflammation characteristic of psoriasis[2]. Recent research has further elucidated the chronic inflammatory underpinnings of psoriasis, underscoring the immune system's central role in its pathophysiology[3]. The distinct leukocyte profile observed in the peripheral blood of psoriasis patients is characterized by a marked increase in neutrophil counts[4]. The recognition of the platelet-to-lymphocyte ratio (PLR) as a rapid and reliable indicator for identifying subclinical inflammatory diseases like systemic lupus erythematosus and heart failure is also of significant clinical relevance[5]. This suggests that PLR may have potential diagnostic value in the context of psoriasis as well. The neutrophil-percentage-to-albumin ratio (NPAR) is a compelling inflammatory biomarker that integrates the quantities of albumin and neutrophils. This composite index has demonstrated significant prognostic value, particularly in predicting mortality in critical conditions including acute myocardial infarction (AMI)[6], cardiogenic shock[7], coronary artery disease[8], and heart failure in the intensive care unit[9]. Similarly, other novel hematological indices such as the neutrophil-to-high-density lipoprotein cholesterol ratio (NHR), lymphocyte-to-high-density lipoprotein cholesterol ratio (LHR), monocyte-to-high-density lipoprotein cholesterol ratio (MHR), and platelet-to-high-density lipoprotein cholesterol ratio (PHR) have also emerged as promising inflammatory markers. These ratios are increasingly recognized for their critical roles in the pathogenesis and progression of a wide range of diseases[10-11]. High-density lipoprotein cholesterol (HDL-C) is known for its anti-inflammatory properties. However, both its levels and function are compromised during inflammatory states[11]. Furthermore, HDL-C engages in complex regulatory interactions with various immune cell types[11]. Recent findings indicate that psoriasis patients have higher levels of C-reactive protein (CRP), MHR, neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR), all of which show a positive correlation with disease severity[12]. Interestingly, CRP--a well-known inflammatory biomarker--was found to be uniquely associated with MHR[13]. Although numerous inflammatory biomarkers have been established as correlates of psoriasis, the relationship between psoriasis and NPAR or NHR remains unexplored. This study is the first to investigate the association of NPAR, NHR, and other related inflammatory markers with psoriasis pathogenesis, thereby offering new perspectives for predicting disease progression. 2. Methods 2.1 Population under investigation The survey collected comprehensive data on demographic characteristics, economic conditions, nutritional intake, and general health, creating a valuable dataset for examining public health trends and addressing emerging health concerns. In this study, we utilized publicly available data from five two-year cycles of the National Health and Nutrition Examination Survey (NHANES), covering the periods 2003-2006 and 2009-2014, with a focus on adults aged 20 to 59. A total of 16,575 individuals participated in both the laboratory examinations, which included complete blood count, high-density lipoprotein cholesterol and albumin examination, and completed the Psoriasis questionnaire. Participants were excluded if they had missing psoriasis assessment data, insufficient information to calculate inflammation indices (namely NPAR, NLR, NHR, LHR, PHR, and MHR), or fell outside the designated age range. Ethical clearance for the NHANES project was granted by the National Center for Health Statistics, and all participants provided written informed consent. The final analysis included 432 participants with psoriasis and 16,143 without psoriasis (Figure 1). Figure 1. Participant selection flowchart for this study. 2.2 Measurement of Systemic Inflammatory Indicators: NPAR, NHR, LHR, PHR, and MHR The relevant laboratory measures were obtained from the NHANES database. HDL-C levels were assessed using an automatic device, with venous blood samples collected after an 8-hour fast. The standard reference range for HDL-C is 1.3–1.5 mmol/L for females and 1.0–1.5 mmol/L for males. White blood cell classification was performed using the Coulter VCS system, which employs automated mixing and dilution for sample preparation, as well as cell counting and molecular weight analysis. The ratios (NPAR, NHR, LHR, PHR, MHR and NLR) were calculated using the following formulas: NPAR: (Percent neutrophils of total leukocyte count [%]) × 100 / Albumin (g/dL); NHR: Neutrophil counts (10^9/L) / HDL-C (mmol/L); LHR: Lymphocyte counts (10^9/L) / HDL-C (mmol/L); PHR: Platelet counts (10^9/L) / HDL-C (mmol/L); MHR: Monocyte counts (10^9/L) / HDL-C (mmol/L); NLR: Neutrophil counts (10^9/L)/Lymphocyte counts (10^9/L). Participants were stratified into four groups--Quantile 1, Quantile 2, Quantile 3, and Quantile 4--based on the quartile ranges of NPAR, NHR, LHR, PHR, MHR, and NLR. 2.3 Psoriasis definition The diagnosis of psoriasis was based on self-reported data from the "medical conditions" section of the questionnaire. Participants were classified as having psoriasis if they answered "yes" to the question: "Has a doctor ever informed you that you have psoriasis?" and confirmed that the diagnosis was given by a healthcare provider. 2.4 Covariates In this study, a comprehensive set of covariates was carefully selected, covering demographic, clinical, and lifestyle factors. Demographic variables included age, gender (male or female), marital status, educational level (categorized as less than high school, high school graduate, some college or associate's degree, and college graduate or above), race/ethnicity (non-Hispanic White, non-Hispanic Black, Mexican American, and other racial/ethnic groups), and the poverty-to-income ratio (PIR). Medical comorbidities consisted of hypertension, hyperlipidemia, diabetes, cardiovascular disease (CVD), and cancer. Lifestyle and health-related factors included body mass index (BMI), smoking status (defined as having smoked at least 100 cigarettes in one's lifetime), and alcohol use (defined as consumption of at least 12 alcoholic beverages in the past year). Diagnoses of diabetes and CVD were based on self-reported physician-confirmed diagnoses. Specifically, diabetes was defined as a previous medical diagnosis of the condition. CVD was considered present if participants reported a history of heart failure, coronary artery disease (CAD), angina, myocardial infarction, or stroke. Hyperlipidemia was defined according to the National Cholesterol Education Program (NCEP) guidelines, incorporating any of the following: LDL cholesterol ≥ 4.1 mmol/L, HDL-C ≤ 1.0 mmol/L in men or ≤ 1.3 mmol/L in women, triglycerides ≥ 2.3 mmol/L, total cholesterol ≥ 6.2 mmol/L, or current use of cholesterol-lowering medication. Hypertension was defined as an average systolic blood pressure ≥ 130 mmHg, diastolic blood pressure ≥ 80 mmHg, and/or current use of antihypertensive medication. Laboratory measures included neutrophil count, lymphocyte count, albumin, monocyte count, total cholesterol, and triglycerides. 2.5 Statistical analysis The statistical analyses in this study were conducted in accordance with NHANES guidelines, incorporating appropriate sample weights and accounting for the complex survey design, including clustering and stratification. Inflammatory biomarkers were categorized into quartiles, and baseline demographic and clinical characteristics across these quartiles were compared using Chi-square tests for categorical variables and t-tests for continuous variables. To evaluate the association between inflammatory biomarkers and psoriasis, three multivariable logistic regression models were constructed: Model 1: Unadjusted, examining the crude association; Model 2: Adjusted for demographic variables (age, gender, and race/ethnicity); Model 3: Further adjusted for socioeconomic factors (PIR and education level), lifestyle variables (smoking status and alcohol use), marital status, and comorbid conditions (diabetes, hypertension, hyperlipidemia, cancer, and cardiovascular disease). A trend test was performed across quartiles of each inflammatory biomarker to assess dose-response relationships. Subgroup analyses were conducted to evaluate potential effect modification by demographic, socioeconomic, and clinical factors. To investigate potential nonlinear associations, we applied smoothing curves fitted by generalized additive models (GAMs). Threshold effects were assessed using segmented regression models, which were compared against linear models via log-likelihood ratio tests. Breakpoints were identified through an iterative recursive algorithm. The discriminative ability of each inflammatory marker for psoriasis was evaluated using the area under the receiver operating characteristic curve (AUC-ROC). A two-sided p-value < 0.05 was considered statistically significant. All analyses were performed using R software (version 4.2) and the EmpowerStats package (version 5.0) to ensure reproducibility and methodological rigor. 3. Results 3.1 Baseline characteristics Of the 16,575 participants included in the analysis, 432 (2.61%) reported a prior diagnosis of psoriasis. The study population comprised 52% females and 48% males, with a mean age of 38.76 ± 11.37 years. The racial/ethnic composition was as follows: 43% non-Hispanic White, 21% non-Hispanic Black, 18% Mexican American, and 7.7% other Hispanic individuals. The mean values for inflammatory biomarkers across the entire cohort were as follows: NPAR, 13.73 ± 2.60; NLR, 2.16 ± 1.05; and NHR, 3.51 ± 1.86. Participants with psoriasis were more likely to have attained higher education levels and were more frequently classified as smokers. They also exhibited a higher prevalence of comorbidities, including hypertension, hyperlipidemia, and cancer, with all differences being statistically significant (p < 0.05; see Table 1). Table 1: The baseline characteristics of participants enrolled in the NHANES cycles spanning from 2003-2006 and 2009-2014. Variables Overall Psoriasis P-value (n=16575) NO (n=16143) YES (n=432) Gender, n (%) 0.037 Male 7,945 (48%) 7,714 (48%) 231 (55%) Female 8,630 (52%) 8,429 (52%) 201 (45%) Age, Mean ± SD 38.76± (11.37) 38.75± (11.38) 39.20± (11.31) 0.495 Age strata, n (%) 0.134 20-39 8,626 (52%) 8,418 (52%) 208 (48%) 40-59 7,949 (48%) 7,725 (48%) 224 (52%) Race, n (%) 0.613 Mexican American 2,911 (18%) 2,827 (18%) 84 (19%) Other Hispanic 1,283 (7.7%) 1,255 (7.8%) 28 (7.2%) Non-Hispanic White 7,127 (43%) 6,948 (43%) 179 (40%) Non-Hispanic Black 3,524 (21%) 3,429 (21%) 95 (20%) Other Race 1,730 (10%) 1,684 (10%) 46 (13%) Education level, n (%) 0.003 Less than 9th grade 1,294 (8.2%) 1,247 (8.1%) 47 (12%) 9-11th grade 2,400 (15%) 2,339 (15%) 61 (13%) High school graduate 3,732 (23%) 3,650 (23%) 82 (17%) Some college or associate degree 5,237 (31%) 5,109 (31%) 128 (28%) College graduate or above 3,912 (23%) 3,798 (23%) 114 (30%) Marital status, n (%) 0.639 Married/Living with a partner 10,126 (61%) 9,855 (61%) 271 (63%) Divorced/Separated/Widowed 2,409 (15%) 2,339 (15%) 70 (15%) Never married 4,040 (25%) 3,949 (25%) 91 (22%) Income-to-poverty ratio, n (%) 0.070 ≤1.3 5,327 (33%) 5,197 (33%) 130 (31%) 1.3-3.5 6,086 (37%) 5,933 (37%) 153 (33%) >3.5 5,162 (30%) 5,013 (29%) 149 (35%) BMI, n (%) 0.502 <25 5,197 (35%) 5,079 (35%) 118 (32%) 25-30 5,342 (34%) 5,199 (34%) 143 (34%) ≥30 6,036 (31%) 5,865 (31%) 171 (34%) Smoking, n (%) <0.001 Yes 7,086 (44%) 6,860 (44%) 226 (54%) No 9,489 (56%) 9,283 (56%) 206 (46%) Alcohol use, n (%) 0.984 Yes 12,351 (79%) 12,030 (79%) 321 (79%) No 4,224 (21%) 4,113 (21%) 111 (21%) Hypertension, n (%) 0.003 Yes 3,683 (22%) 3,550 (22%) 133 (30%) No 12,892 (78%) 12,593 (78%) 299 (70%) Hyperlipidemia, n (%) <0.001 Yes 4,670 (30%) 4,505 (29%) 165 (40%) No 11,905 (70%) 11,638 (71%) 267 (60%) Cardiovascular disease, n (%) 0.514 Yes 187 (1.1%) 176 (1.1%) 11 (1.4%) No 16,388 (99%) 15,967 (99%) 421 (99%) Cancer, n (%) 0.016 Yes 638 (5.0%) 607 (4.9%) 31 (8.3%) No 15,937 (95%) 15,536 (95%) 401 (92%) Diabetes, n (%) 0.594 Yes 1,075 (5.5%) 1,041 (5.5%) 34 (6.2%) No 15,500 (94%) 15,102 (94%) 398 (94%) C 7.32± (2.20) 7.33± (2.21) 7.11± (1.98) 0.144 Platelet (103 cells/μL) 255.92± (65.20) 255.79± (65.13) 260.29± (67.21) 0.310 Lymphocyte (103 cells/μL) 2.17± (0.81) 2.17± (0.82) 2.10± (0.66) 0.211 Monocyte (103 cells/μL) 0.55± (0.18) 0.54± (0.18) 0.55± (0.16) 0.171 Neutrophil (103 cells/μL) 4.37± (1.74) 4.36± (1.74) 4.52± (1.65) 0.059 Neutrophils percent (%) 58.52± (8.97) 58.48± (8.97) 59.80± (8.63) 0.004 Albumin (g/L) 42.98± (3.50) 42.99± (3.50) 42.75± (3.34) 0.147 HDL-C (mmol/L) 1.37± (0.41) 1.37± (0.41) 1.34± (0.41) 0.179 NPAR (dL/g) 13.73± (2.60) 13.72± (2.60) 14.11± (2.56) 0.003 NLR (109/mmol) 2.16± (1.05) 2.16± (1.05) 2.29± (0.94) <0.001 NHR (109/mmol) 3.51± (1.86) 3.51± (1.86) 3.70± (1.77) 0.014 LHR (109/mmol) (0.94) (0.82) (109/mmol) MHR (109/mmol) < 0.05 was statistically National Health and Nutrition Examination body mass high-density lipoprotein NPAR: neutrophil-percentage-to-albumin NLR: neutrophil-to-lymphocyte NHR: neutrophil-to-high-density lipoprotein cholesterol LHR: lymphocyte-to-high-density lipoprotein cholesterol PHR: platelet-to-high-density lipoprotein cholesterol MHR: lipoprotein cholesterol Psoriasis a correlation with inflammation This analysis evaluated the association between psoriasis and systemic inflammatory biomarkers using three adjusted models In the each increase in NPAR was associated with a higher of psoriasis This association significant after for demographic factors in Model and further for socioeconomic, and clinical covariates in Model analysis of NPAR also demonstrated a statistically significant dose-response relationship with psoriasis across all NHR, each increase was associated with a increase in the of psoriasis in Model The association significant after demographic in Model but was and significant in the adjusted Model No significant were observed between psoriasis and LHR, PHR, or MHR in any of the additive models nonlinear between NPAR, NLR, NHR, and psoriasis. Threshold analysis identified at NPAR NLR and NHR the of NPAR was associated with psoriasis Similarly, a value of NLR a positive association with psoriasis (Figure Table 2: between systemic inflammatory and logistic regression analysis of NHANES 2003-2006 and 2009-2014. Model Model Model NPAR for trend 0.004 for trend 0.004 NLR for trend 0.003 NHR for trend LHR for trend for trend MHR for trend Model 1: No covariates were Model 2: Age, gender, and were Model 3: Age, gender, marital status, education level, ratio, BMI, alcohol use, diabetes, cardiovascular disease, hypertension, hyperlipidemia, and were < 0.05 was statistically significant. NPAR: neutrophil-percentage-to-albumin NPAR by NLR: neutrophil-to-lymphocyte NHR: neutrophil-to-high-density lipoprotein cholesterol LHR: lymphocyte-to-high-density lipoprotein cholesterol PHR: platelet-to-high-density lipoprotein cholesterol MHR: lipoprotein cholesterol Table 3: Threshold effect analysis of systemic inflammatory on psoriasis using a linear regression in Model 3. Threshold effect analysis Psoriasis P-value NPAR effect of NPAR < <0.001 ratio test <0.001 effect of < <0.001 ratio test <0.001 NLR effect of NLR < <0.001 ratio test <0.001 NHR effect of NHR < ratio test Adjusted for age, gender, marital status, education level, ratio, BMI, alcohol use, diabetes, cardiovascular disease, hypertension, hyperlipidemia, and cancer. < 0.05 was statistically significant. NPAR: neutrophil-percentage-to-albumin NPAR by NLR: neutrophil-to-lymphocyte NHR: neutrophil-to-high-density lipoprotein cholesterol Figure 2. curve for the between systemic inflammatory and psoriasis. ratio neutrophil-to-lymphocyte ratio neutrophil-to-high-density lipoprotein cholesterol ratio lymphocyte-to-high-density lipoprotein cholesterol ratio platelet-to-high-density lipoprotein cholesterol ratio monocyte-to-high-density lipoprotein cholesterol ratio Subgroup analysis Subgroup analyses were conducted to evaluate the between inflammatory markers and psoriasis by demographic and clinical including age, gender, education level, marital status, BMI, smoking status, alcohol use, hypertension, hyperlipidemia, cancer, and diabetes (Figure No significant effects were observed between any of these covariates and NPAR in to psoriasis However, stratified analyses that NHR was associated with higher of psoriasis Specifically, females and individuals with higher in the quartile of NHR Similarly, the NLR and alcohol a trend an of psoriasis, these not statistical Figure 3. Subgroup analysis of the association between quartile of the three ratios and the prevalence of psoriasis. ratio neutrophil-to-lymphocyte ratio lipoprotein cholesterol ratio All models were adjusted for age, gender, marital status, education level, ratio, BMI, alcohol diabetes, cardiovascular disease, hypertension, hyperlipidemia, and cancer, with the excluded from each Results are as ratios by with as analysis calculated the values to evaluate the of systemic inflammatory for psoriasis (Figure The that the values for NHR, NLR, and NPAR exhibited discriminative ability compared to the other inflammatory markers as in Table the values for NPAR, NHR, and NLR were all statistically significant (p < Figure curve analysis of systemic inflammatory biomarkers for the diagnosis of psoriasis. Table values of systemic inflammatory for the in NHR <0.001 MHR LHR 0.003 NLR <0.001 NPAR <0.001 <0.001 < 0.05 was statistically significant. area the PHR: platelet-to-high-density lipoprotein cholesterol NHR: neutrophil-to-high-density lipoprotein cholesterol MHR: lipoprotein cholesterol LHR: lymphocyte-to-high-density lipoprotein cholesterol NLR: neutrophil-to-lymphocyte NPAR: neutrophil-percentage-to-albumin NPAR by This study identified significant between levels of NPAR, NLR, and NHR and of psoriasis In significant were observed for LHR, PHR, or for demographic, socioeconomic, and clinical age, gender, marital status, BMI, alcohol use, diabetes, hypertension, hyperlipidemia, and association between NHR and psoriasis was statistically significant. These findings are with previous a nonlinear relationship between NLR and both the prevalence and of In this study, we for the first a correlation between NPAR, NHR and an of psoriasis. study the role of NPAR as a and biomarker of systemic research has demonstrated its value in a range of conditions, including acute cardiogenic myocardial infarction, metabolic disease, and a critical of blood cells, are in the inflammatory response. on the other anti-inflammatory and that are by inflammatory in In individuals with and frequently a findings NPAR as a and of psoriasis The of neutrophil and albumin valuable clinical NPAR other inflammatory blood such as the NLR and ratio, in predicting as by data from the NHANES The NLR as a valuable and indicator of systemic from laboratory an of inflammatory status, particularly in patients following The NLR integrates and immune innate by neutrophil and by This clinical as NLR values have been associated with levels of underscoring its as a reliable marker of systemic Furthermore, analyses that individuals in the quartile of NLR as well as or an of psoriasis. These findings the role of smoking and alcohol consumption as significant factors for psoriasis Neutrophils a role in chronic inflammatory and and their in psoriasis is by like In generalized psoriasis, a is a characteristic have reported NLR and platelet-to-lymphocyte ratio in psoriasis these markers not disease a in NLR levels following psoriasis the of NLR levels in disease NPAR is a composite inflammatory marker that integrates neutrophil and albumin a albumin under chronic inflammatory which may the NPAR values observed in patients with psoriasis. Furthermore, albumin levels are less by acute and inflammation more This NPAR a more indicator of psoriasis disease compared to HDL-C and in based inflammatory emerging MHR, NHR, and by or counts by HDL-C between and NHR, in particular, has emerged as a promising biomarker that integrates inflammatory and metabolic offering valuable into their that the NHR has high for a range of systemic conditions, including acute hypertension, cardiovascular and However, after for potential the association between NHR and psoriasis prevalence was not statistically significant. findings indicate that NPAR and NLR may as biomarkers for psoriasis and its cardiovascular disease and metabolic of systemic NLR has been to cardiovascular and NPAR, neutrophil and albumin may chronic inflammatory and metabolic such as in These markers in identifying psoriasis patients at for CVD or metabolic syndrome, and more their in and clinical This study has and A is the substantial sample which the of the findings and with previous In the for a wide range of covariates the of the this is the first study to investigate the relationship between psoriasis and novel inflammatory such as NPAR and However, be The and the between inflammatory markers and psoriasis remains or are to and some analyses sample as the analysis of in the NLR may have in and statistical These findings be with and in is the on self-reported psoriasis which may the of data on psoriasis ability to evaluate between inflammatory markers and disease the clinical of the analysis. NPAR and NLR show a significant positive correlation with psoriasis prevalence and other inflammatory as PHR, MHR, and both and discriminative their potential in the clinical and of psoriasis.
Source: Frontiers in Immunology
Authors: Huizi Xiong, Zengyang Yu
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W4415958418