Underperformance of clinical risk scores in identifying imaging-based high cardiovascular risk in psoriasis: results from two observational cohorts.

AIMS: We aimed to evaluate whether traditional risk scores [short-term, 'psoriasis-modified' (multiplied by 1.5) and lifetime] were able to capture high cardiovascular disease (CVD) risk as defined by the presence of atherosclerotic plaques in coronary, femoral, or carotid arteries in psoriasis. METHODS AND RESULTS: We used two prospectives obseravational cohorts. European cohort: femoral and carotid atherosclerotic plaques were evaluated by ultrasound in 73 psoriasis patients. Lifetime CVD risk (LTCVR) was evaluated with QRISK-LT; short-term CVD risk was evaluated with SCORE and psoriasis-modified SCORE. American cohort: 165 patients underwent coronary computed tomography angiography to assess presence of coronary plaques. LTCVR was evaluated with atherosclerotic cardiovascular disease (ASCVD-LT) lifetime; short-term CVD risk was evaluated with ASCVD and psoriasis-modified ASCVD. European cohort: subclinical atherosclerosis was present in 51% of patients. QRISK-LT identified 64% of patients with atherosclerosis missing a high proportion (35%) with atheroma plaque (P < 0.05). The percentage of patients with atherosclerosis identified by QRISK-LT was significantly higher than those detected by SCORE (0%) and modified SCORE (10%). American cohort: subclinical atherosclerosis was present in 54% of patients. ASCVD-LT captured 54% of patients with coronary plaques missing a high proportion (46%) with coronary plaque (P < 0.05). The percentage of patients with atheroma plaques detected with ASCVD and modified ASCVD were only 20% and 45%, respectively. CONCLUSIONS: Application of lifetime, short-term and 'psoriasis-modified' risk scores did not accurately capture psoriasis patients at high CVD risk.

Subclinical Liver Disease Is Associated with Subclinical Atherosclerosis in Psoriasis: Results from Two Observational Studies.

Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n = 76 psoriasis participants and 76 controls), nonalcoholic fatty liver disease, assessed by the sonographic hepatorenal index, was more prevalent in psoriasis than in controls (61% vs. 45%; P = 0.04). Participants with psoriasis with nonalcoholic fatty liver disease had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than participants with psoriasis without nonalcoholic fatty liver disease (61% vs. 23%; P = 0.006) and controls with nonalcoholic fatty liver disease (61% vs. 32%; P < 0.05). Sonographic hepatorenal index was a determinant of subclinical atherosclerosis in psoriasis (OR = 3.5; P = 0.01). In the United States cohort (n = 162 participants with psoriasis who underwent positron emission tomography and coronary computed tomography angiography), those with high hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake had higher noncalcified (1.3 [0.49 mm2] vs. 1.0 [0.40 mm2]), fibrofatty (0.23 [0.15 mm2] vs. 0.11 [0.087 mm2]), and lipid-rich necrotic core (4.3 [2.3 mm2] vs. 3.0 [1.7 mm2]) coronary burden (all P < 0.001). Hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake associated with noncalcified (ß = 0.28; P < 0.001), fibrofatty (ß = 0.49; P < 0.001), and lipid-rich necrotic core (ß = 0.28; P = 0.003) burden. These results show the downstream cardiovascular effects of subclinical liver disease in psoriasis.

Impact of Biological Agents on Imaging and Biomarkers of Cardiovascular Disease in Patients with Psoriasis: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: The effect of biologics on the risk for cardiovascular disease in patients with psoriasis is still unclear despite their widespread use. OBJECTIVE: The objective of this study was to examine the impact of licensed biological therapies on imaging and biomarkers of cardiovascular disease risk in patients with psoriasis by a systematic review and meta-analysis of placebo-controlled trials. METHODS: A comprehensive search of studies published before 1 June 2020 was performed in Medline-Ovid, EMBASE, and CENTRAL using a predefined strategy to identify relevant articles. RESULTS: Five studies were included for the final examination, and two studies were included in the meta-analysis. We did not find a significant reduction in aortic vascular inflammation in patients treated with adalimumab compared with those who received placebo at weeks 12-16. There was no beneficial effect on imaging biomarkers (aortic vascular inflammation or flow-mediated dilatation) of cardiovascular disease risk in patients exposed to biological therapies (adalimumab and secukinumab) compared with those exposed to placebo, except for ustekinumab showing a reduction in aortic vascular inflammation at week 12 but not at week 52 after the open-label extension period. The strongest reduction in blood-based cardiometabolic risk biomarkers was observed with adalimumab (CRP, TNF-α, IL-6, and GlycA) and phototherapy (CRP and IL-6) compared with that observed with placebo. CONCLUSIONS: Randomized controlled trials show that ustekinumab reduces aortic vascular inflammation and that TNF-α inhibitors and phototherapy reduce CRP and IL-6. These surrogate marker findings require randomized controlled trials evaluating cardiovascular events to inform clinical practice.

Bone mineral density, bone turnover markers and cytokines in alcohol-induced cirrhosis.

AIMS: Liver cirrhosis is a risk factor for osteoporosis. However, the pathogenesis of the bone mass loss in patients with alcohol-induced cirrhosis (AC) is not well understood. Serum concentrations of soluble tumour necrosis factor receptor (sTNF-R55), neopterin and soluble interleukin 2 receptor (sIL-2R), activation markers of cellular immunity, correlate with clinical activity and severity of the AC. The aim of this study is to evaluate the association of these soluble markers with the development of osteoporosis in patients with AC. METHODS: We studied 33 consecutive patients with AC and 24 healthy volunteers. Bone mineral density (BMD) was measured by X-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN). Neopterin was measured by radioimmunoassay. Serum concentrations of sTNF-R55 and sIL-2R were measured by enzyme immunoassay. We also determined serum levels of osteocalcin and bone alkaline phosphatase as biochemical markers of bone formation, and deoxypyridinoline urinary excretion (D-Pyr) as marker of bone resorption. RESULTS: Patients with AC had reduced BMD (expressed as z-score) in all sites (LS: P < 0.001 and FN: P < 0.05). Serum concentrations of sTNF-R55 were significantly higher in patients with both AC and osteoporosis than in those with only AC (P < 0.001). Serum levels of sTNF-R55 positively correlated with D-Pyr urinary excretion (r = 0.354; P = 0.01). Serum levels of sIL-2R were significantly higher in patients with both AC and osteoporosis than in those with only AC (P < 0.05). CONCLUSIONS: There is a relation between activation of the cellular immunity and osteoporosis in AC. Bone mass loss could be related to the increased bone resorption found in these patients.

Subclinical atherosclerosis in psoriasis. Usefulness of femoral artery ultrasound for the diagnosis, and analysis of its relationship with insulin resistance.

BACKGROUND: Psoriasis is associated with an increased risk of cardiovascular disease (CVD) at younger ages that is not identifiable by traditional risk factors. Screening for subclinical atherosclerosis with ultrasound has only been investigated in carotid arteries. Femoral artery ultrasound has never been considered for this purpose. The link between psoriasis and accelerated atherosclerosis has not yet been established. OBJECTIVE: To study the usefulness of femoral artery ultrasound for the detection of subclinical atherosclerosis in psoriasis. We also investigated its possible relationship with changes in insulin resistance. METHODS: We conducted a cross-sectional study in 140 participants, 70 patients with moderate-to-severe psoriasis and 70 healthy controls, matched 1:1 for age, sex, and BMI. Femoral and carotid atherosclerotic plaques were evaluated by ultrasonography. Insulin resistance was assessed by the homeostasis model assessment method (HOMA-IR). RESULTS: Femoral atherosclerotic plaque prevalence was significantly higher in patients with psoriasis (44.64%) than in controls (19.07%) (p<0.005), but no significant difference was found in carotid plaque prevalence (p<0.3). Femoral plaques were significantly more prevalent than carotid plaques (21.42%) among patients with psoriasis (p<0.001). In the regression analysis, insulin resistance was the most influential determinant of atherosclerosis in psoriasis and C-reactive protein the most significant predictor of insulin resistance. CONCLUSIONS: Ultrasound screening for femoral atherosclerotic plaques improves the detection of subclinical atherosclerosis in patients with psoriasis, whereas the study of carotid arteries is not sufficiently accurate. Insulin resistance appears to play a greater role in the development of atherosclerosis in these patients in comparison to other classical CVD risk factors.

Insulin resistance in lean and overweight non-diabetic Caucasian adults: Study of its relationship with liver triglyceride content, waist circumference and BMI.

AIMS: Insulin resistance is the pathophysiological precursor of type 2 diabetes mellitus (DM-2), and its relationship with non-alcoholic fatty liver disease (NAFLD) has been widely studied in patients with obesity or metabolic syndrome using not only ultrasound but also liver biopsies or proton magnetic resonance spectroscopy (H1-MRS) to assess liver fat content. In contrast, there are no studies on insulin resistance and NAFLD in lean or overweight Caucasian individuals using H1-MRS or liver biopsies for the quantification of hepatic triglyceride content. Our objectives were to study the presence of insulin resistance in lean and overweight Caucasian adults and investigate its possible relationship with liver triglyceride content, waist circumference (as proxy of visceral adiposity), BMI, and cardiometabolic risk factors. METHODS: A cross-sectional study was conducted in 113 non-obese, non-diabetic individuals classified as overweight (BMI 25-29.9 kg/m2) or lean (BMI 19.5-24.9 kg/m2). Hepatic triglyceride content was quantified by 3T H1-MRS. NAFLD was defined as hepatic triglyceride content >5.56%. Insulin resistance (HOMA-IR), serum adiponectin, and tumor necrosis factor (TNF) were determined. RESULTS: HOMA-IR was significantly correlated with hepatic triglyceride content (r:0.76; p<0.0001). The lean-with-NAFLD group had significantly higher HOMA-IR (p<0.001) and lower serum adiponectin (p<0.05) than the overweight-without-NAFLD group. Insulin resistance was independently associated with NAFLD but not with waist circumference or BMI. Regression analysis showed hepatic triglyceride content to be the most important determinant of insulin resistance (p<0.01). CONCLUSIONS: Our findings suggest that NAFLD, once established, seems to be involved in insulin resistance and cardio-metabolic risk factors above and beyond waist circumference and BMI in non-obese, non-diabetic Caucasian individuals.

Diagnostic accuracy of serum alanine aminotransferase as biomarker for nonalcoholic fatty liver disease and insulin resistance in healthy subjects, using 3T MR spectroscopy.

Recognition of the close relationship of nonalcoholic fatty liver disease (NAFLD) with diabetes mellitus 2, obesity, metabolic syndrome, and cardiovascular disease has stimulated growing interest in NAFLD as a public health problem. Serum alanine aminotransferase (ALT) has been proposed as a marker of NAFLD, but levels are within the range currently considered "normal" in a large proportion of NAFLD subjects.The aim of the study was to determine the diagnostic accuracy of serum ALT for identifying individuals with NAFLD, using 3-Tesla (T) magnetic resonance spectroscopy (H-MRS).A cross-sectional study was conducted in 129 healthy subjects. Liver triglyceride content was quantified by H-MRS. NAFLD was defined as liver triglyceride content greater than 5.56%.Liver triglyceride content was >5.56% in 79 participants (NAFLD) and lower in the remaining 50 (normal). Serum ALT levels correlated positively with liver triglyceride content (r = 0.58, P < .001), Homeostatic Model Assessment for Insulin Resistance (r = 0.32, P < .01), and fasting insulin (r = 0.31, P < .01), and inversely correlated with adiponectin (r = 0.35, P < .01) and high-density lipoprotein cholesterol (r = 0.32, P < .01). Regression analysis showed that serum ALT was the best predictor of NAFLD (P < .01). Optimal serum ALT cut-off to predict NAFLD was 23 IU/L (area under receiver-operating characteristic curve: 0.93; sensitivity: 0.94; specificity: 0.72).This study shows that serum ALT is a sensitive and accurate biomarker of NAFLD if the "normal" ALT value is revised and established at a lower level. An ALT threshold of 23 IU/L identified 94% of individuals with NAFLD in the present series, using 3-T H-MRS for liver triglyceride quantification.

The role of Toll-like receptor polymorphisms in acute pancreatitis occurrence and severity.

OBJECTIVES: Toll-like receptors (TLRs) are damage-associated molecular patterns receptors, which are essential in the activation of the inflammasome cascade, required for the initiation of inflammation. We hypothesized that changes in the function of these receptors caused by genetic polymorphisms in their encoding genes could determine acute pancreatitis (AP) incidence or severity. METHODS: Two hundred sixty-nine patients and 269 controls were included. Acute pancreatitis diagnosis criteria were abdominal pain, increased serum amylase levels, and positive findings on abdominal imaging. The patients were observed until discharge. Blood samples were obtained, determining the following TLRs: TLR1 rs5743611, TLR2 rs5743704, TLR3 rs3775291, TLR3 rs5743305, TLR4 rs4986790, TLR4 rs4986791, TLR5 rs5744174, TLR6 rs5743795, TLR7 rs2302267, TLR9 rs352140, and TLR10 rs4129009. RESULTS: No TLR polymorphism was related to AP incidence. Regarding severity, CC genotype patients in TLR3 rs3775291 had an increased risk for severe pancreatitis (CC odds ratio [OR], 2.426; P = 0.015). In addition, TLR6 rs5743795 GG genotype patients had a lower risk for severe AP (GG OR, 0.909; P < 0.05). Intensive care unit admission was related to TLR5 rs5744174 homozygote TT carriers (TT OR, 3.367; P = 0.036). CONCLUSIONS: Our article points to genetic polymorphisms in TLR3 and TLR6 as having a plausible role in the occurrence of severe AP.

Osteoporosis, mineral metabolism, and serum soluble tumor necrosis factor receptor p55 in viral cirrhosis.

Liver cirrhosis is a risk factor for osteoporosis. Nevertheless, little is known about the mechanisms of bone mass loss in patients with viral cirrhosis. TNFalpha is a potent bone-resorbing agent. Serum concentrations of soluble TNF receptor p55 (sTNFR-55) correlate with clinical activity in liver cirrhosis. Our aim was to evaluate the possible role of sTNFR-55 in the pathogenesis of osteoporosis in patients with viral cirrhosis and its relationship with bone turnover markers. We studied 40 consecutive patients with viral cirrhosis and no history of alcohol intake and 26 healthy volunteers. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN). Patients with viral cirrhosis had reduced BMD (expressed as the z-score) in all sites [LS, -1.5 +/- 0.22 (P < 0.001); FN, -0.37 +/- 0.15 (P < 0.01)]. Serum concentrations of sTNFR-55 and urinary deoxypyridinoline, a biochemical marker of bone resorption, were significantly higher in patients with osteoporosis than in patients without osteoporosis (P < 0.001 and P < 0.05, respectively). Serum levels of sTNFR-55 correlated inversely with BMD in LS (r = -0.62; P < 0.005) and FN (r = -0.47; P < 0.05) and positively with urinary deoxypyridinoline (r = 0.72, P < 0.001). Our findings show that high serum concentrations of sTNFR-55 play a role in the pathogenesis of viral cirrhosis-associated bone mass loss and provide evidence of increased bone resorption related to the high serum sTNFR-55 levels.

[Prevalence of vitamin D deficiency in populations at risk for osteoporosis: impact on bone integrity]. / Elevada prevalencia de déficit de vitamina D en poblaciones con riesgo de osteoporosis: un factor relevante en la integridad ósea.

BACKGROUND: Nowadays, severe deficiency of vitamin D is not a common finding in most developed countries. However, the prevalence of vitamin D insufficiency is relatively high and it can contribute to the descent of bone mass in osteoporosis risk populations. The objective of our study was to evaluate the prevalence of vitamin D insufficiency in postmenopausal women (PMW), patients with inflammatory bowel disease (IBD) and corticosteroid-dependent asthmatic patients (CAP) and to analyze its relationship with bone mineral density (BMD) and calciotropic hormones. PATIENTS AND METHOD: We studied 299 patients (PMW: 161; IBD: 61; CAP: 77). In all cases, serum levels of PTH and 25OHD were determined and the BMD (DXA, Hologic QDR1000) in lumbar spine (LS) and femoral neck (FN) was measured. RESULTS: Vitamin D insufficiency (25OHD < 15 ng/ml) was observed in 39.1% patients with PMW, 70.7% patients with IBD and 44.2% patients with CAP. 25OHD concentrations were lower in EII patients (p = 0.003) and PTH concentrations were higher in MPM (p < 0.001). We found a negative correlation between PTH and 25OHD in the overall group and this correlation persisted after considering each group separately. After adjusting for remaining variables, 25OHD was found to be significantly associated with BMD at lumbar spine and/or femoral neck in the three groups. CONCLUSIONS: In populations at risk of osteoporosis, there is a high prevalence of vitamin D insufficiency. This insufficiency has a significant effect on bone integrity.

Sonographic quantification of a hepato-renal index for the assessment of hepatic steatosis in comparison with 3T proton magnetic resonance spectroscopy.

CONTEXT: Nonalcoholic fatty liver disease is the most frequent hepatic disorder in the developed world. Currently, liver biopsy and proton magnetic resonance spectroscopy (H-MRS) are considered the gold standard methods for the quantification of liver fat deposits. OBJECTIVE: To determine whether a Sonographic Hepato-Renal Index (SHRI) calculated using a standard workstation, without a specifically designed software, is an adequate alternative to H-MRS for the quantification of fat liver content and diagnosis of steatosis in the general population. METHODS: A total of 121 volunteers (mean age=46 years, range=21-77 years) were recruited at three medical centers in Granada (Southern Spain) from among individuals attending routine general checkups. All participants were examined by ultrasound and by H-MRS 3T, which served as a reference for the diagnosis of steatosis. The SHRI was calculated as the ratio between the echogenicity of the liver and that of the right renal parenchyma. The validity of the methodology was assessed by receiver operating characteristic curves and correlation tests. RESULTS: The quantitative SHRI showed a strong correlation (Spearman's coefficient=0.89, P<0.001) with the H-MRS 3T. The optimal SHRI cutoff points of 1.21, 1.28, and 2.15 yielded 100% sensitivity for the diagnoses of steatosis greater than 5, 25, and 50%, respectively, with a specificity greater than 70%. CONCLUSION: This study shows that the SHRI is a valid, simple, reliable, and cost-effective screening tool for the identification, assessment, and quantification of hepatic steatosis in the general population.

Bone mineral density and serum levels of soluble tumor necrosis factors, estradiol, and osteoprotegerin in postmenopausal women with cirrhosis after viral hepatitis.

CONTEXT: Cirrhosis after viral hepatitis has been identified as a risk factor for osteoporosis in men. However, in postmenopausal women, most studies have evaluated the effect of primary biliary cirrhosis, but little is known about the effect of viral cirrhosis on bone mass [bone mineral density (BMD)] and bone metabolism. OBJECTIVE: Our objective was to assess the effect of viral cirrhosis on BMD and bone metabolism in postmenopausal women. DESIGN: We conducted a cross-sectional descriptive study. SETTING AND PATIENTS: We studied 84 postmenopausal female outpatients with viral cirrhosis and 96 healthy postmenopausal women from the general community. BMD was measured by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN). RESULTS: The percentage with osteoporosis did not significantly differ between patients (LS, 43.1%; FN, 32.2%) and controls (LS, 41.2%; FN, 29.4%), and there was no difference in BMD (z-score) between groups. Serum concentrations of soluble TNF receptors, estradiol, and osteoprotegerin (OPG) were significantly higher in patients vs. controls (P < 0.001, P < 0.05, and P < 0.05, respectively). No significant difference was observed in urinary deoxypyridinoline. Serum OPG levels were positively correlated with soluble TNF receptors (r = 0.35; P < 0.02) and deoxypyridinoline (r = 0.37; P < 0.05). CONCLUSIONS: This study shows that bone mass and bone resorption rates do not differ between postmenopausal women with viral cirrhosis and healthy postmenopausal controls and suggests that viral cirrhosis does not appear to increase the risk of osteoporosis in these women. High serum estradiol and OPG concentrations may contribute to preventing the bone loss associated with viral cirrhosis in postmenopausal women.