Serum Levels of PCSK9 Are Increased in Patients With Active Ulcerative Colitis Representing a Potential Biomarker of Disease Activity: A Cross-sectional Study.

BACKGROUND/GOAL: Ulcerative colitis (UC) is characterized by chronic inflammation and progressive course, with potential extraintestinal complications including cardiovascular mortality. Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels have been recently recognized as biomarkers of low-grade inflammation and cardiovascular disease. The aim of our study was to evaluate PCSK9 levels in patients with UC and different degrees of disease activity. METHODS: We prospectively recruited consecutive patients with UC attending our center at the University Hospital of Padua. Demographics, clinical characteristics, and biochemical data, including PCSK9, high sensitivity C-reactive protein, and fecal calprotectin, were recorded. Moreover, endoscopic procedures were performed in all subjects. RESULTS: We included 112 patients with UC (mean age=52.62±12.84 y; 52.62% males). Patients with UC and abnormal fecal calprotectin (≥250 µg/g) and/or C-reactive protein (≥3 mg/L) had greater levels of PCSK9 compared with UC patients with normal fecal calprotectin and high sensitivity C-reactive protein ( P =0.03 and 0.005, respectively). Higher endoscopic scores in UC were characterized by greater levels of PCSK9 ( P =0.03). Furthermore, we found a positive correlation between PCSK9 levels and fecal calprotectin ( r =0.18, P =0.04), endoscopic Mayo Score ( r =0.25, P =0.007), and UC-Riley Index ( r =0.22, P =0.01). We also found a positive correlation between PCSK9 levels and both total and low-density lipoprotein cholesterol values ( P <0.05). CONCLUSIONS: Serum PCSK9 levels are increased in patients with biochemical and endoscopic evidence of active disease in UC. Further longitudinal studies are necessary to evaluate the role of PCSK9 as a potential biomarker of disease activity and cardiovascular risk in UC.

Bariatric surgery improves atherogenic LDL profile by triglyceride reduction.

BACKGROUND: Small dense low-density lipoprotein (LDL) are atherogenic particles frequently observed in obese patients. Fatty acids modulate LDL. Objective of this study was to determine the relations between plasma phospholipid fatty acid composition and the presence of small dense LDL particles in morbidly obese patients treated with laparoscopic gastric banding (LAGB). METHODS: Small dense LDL, plasma lipids, lipoproteins, apoproteins, and phospholipid fatty acid composition (a marker of dietary fatty acid intake) were quantified before and 12 months after surgery in four men and 11 women who were morbidly obese and (BMI > 40 kg/m(2)) eligible for surgery, consecutively treated with LAGB at the Department of Medical and Surgical Sciences of the University of Padova. RESULTS: BMI was 48.3 +/- 4.8 kg/m(2) before and 36.1 +/- 5.5 kg/m(2) after LAGB. Plasma triglycerides and apoprotein E levels significantly decreased, while HDL cholesterol significantly increased after LAGB. A reduction of small dense LDL with an increase of LDL relative flotation (0.34 +/- 0.04 before vs 0.38 +/- 0.03 after LAGB, p < 0.001) was also observed. These modifications were neither related to weight reduction nor to changes in phospholipid fatty acid composition, but they were associated to triglyceride reduction, which explained 76.7% of the LDL relative flotation variation. CONCLUSION: Weight loss obtained by LAGB in morbidly obese subjects was accompanied by triglyceride reduction, high-density lipoprotein increase, and an improvement of the atherogenic LDL profile. Triglyceride reduction, but not the extent of weight loss or dietary fatty acid modifications, is the determinant of modifications of LDL physical properties in these patients.

Lipid and phospholipid profile after bowel resection for Crohn's disease.

BACKGROUND AND AIM: Chronic inflammation, impaired intestinal adsorption, and bowel resection may have an impact on lipid metabolism before and after intestinal surgery for Crohn's disease (CD). The aim of this prospective study was to define the impact of intestinal surgery for CD on plasma phospholipid fatty acid (FA) composition and of serum plasma lipoprotein concentrations and to investigate the role of CD recurrence on lipid parameters. MATERIALS AND METHODS: Twenty-four consecutive patients who had intestinal surgery for CD since December 2004 to March 2006 were enrolled in this prospective study. The total amount of calorie intake and the quality of the aliments, systemic inflammatory activity, and plasma lipoproteins and phospholipid fatty acid composition were determined at operation and at follow-up. Statistical analysis was performed with pair-matched tests. RESULTS: The median follow-up was 6 (4-20) months. During the follow-up, no significant modification of body mass index was observed. An increase of high-density lipoprotein (HDL) cholesterol (p=0.02) without other modifications in the plasma phospholipid FA composition were evidenced after surgery. The comparison between colectomy and ileo-colonic or ileal resection groups did not show any significant difference in the lipoprotein concentration and phospholipid FA profile. The length of resected bowel did not show any significant correlation with any relevant difference in lipid, phospholipid profile, or in inflammatory parameters. Patients who experienced a recurrence of CD reported significantly higher levels of total (p<0.01), HDL (p=0.01), and low-density lipoprotein cholesterol (p=0.01) were observed in patients in remission than in those with recurrent active disease. CONCLUSIONS: Patients who are submitted to intestinal resection for CD improve their inflammatory status as well as their lipid metabolism, and CD recurrence, but not the extent of bowel resection, is the main predictor of alteration of serum lipid concentration.

Metabolic syndrome and cardiovascular disease in the elderly: the Progetto Veneto Anziani (Pro.V.A.) study.

BACKGROUND AND AIMS: The prevalence of the metabolic syndrome increases with age, although only few data are available about its prevalence in the general elderly population. This study describes the prevalence of the metabolic syndrome in an elderly population, and its association with cardiovascular diseases. METHODS: The Progetto Veneto Anziani (Pro.V.A.) is an observational study of 3,099 subjects aged 65 and older, randomly selected from the general population of Northern Italy. Cardiovascular diseases and metabolic syndrome according to Adult Treatment Panel III were evaluated in 2,910 subjects. RESULTS: The metabolic syndrome was present in 25.6% of men and 48.1% of women. Its prevalence was mainly due to high blood pressure (93%) in both sexes, and to abdominal obesity in 73% of women. The prevalence of cardiovascular diseases was significantly higher among subjects with metabolic syndrome. Together with age and former smoking habits, the metabolic syndrome was significantly associated with cardiovascular diseases. High blood pressure and low HDL were independently associated with cardiovascular diseases in men, and with high fasting plasma glucose and waist circumference in women. CONCLUSIONS: The metabolic syndrome is frequent, and significantly but not independently associated with prevalent cardiovascular diseases in the elderly. In old people, rather than the metabolic syndrome per se, some of its components are independently associated with cardiovascular diseases.

Restorative proctocolectomy for ulcerative colitis: impact on lipid metabolism and adipose tissue and serum fatty acids.

The aim of this prospective study was to evaluate the changes of the metabolism of circulating and storage lipids in patients with ulcerative colitis after restorative proctocolectomy. Fifteen consecutive patients and 15 sex- and age-matched healthy controls were enrolled. Disease activity, diet, inflammatory parameters, plasma lipoprotein concentrations, and fatty acids (FA) of serum phospholipids and of the subcutaneous adipose tissue were assessed at colectomy and at ileostomy closure. In ulcerative colitis patients, total cholesterol and docosahexaenoic acid were lower than in healthy subjects (p < 0.01 and p < 0.05). The median interval between colectomy and ileostomy closure was 6 (range 2-9) months. During that interval, the inflammatory parameters improved, high-density lipoproteins (HDL) cholesterol increased (p < 0.01), and low-density (LDL) cholesterol decreased (p = 0.01). At ileostomy closure, serum arachidonic acid levels were increased (p = 0.04), whereas serum oleic acid level was decreased (p = 0.02). In this interval, no significant alteration, either in serum n-3 FA precursors or in the FA of subcutaneous adipose tissue, was observed. The increase of serum arachidonic acid after colectomy might suggest a lower utilization for inflammatory process. The reduction of LDL cholesterol is an index of malabsorption probably due to the accelerated transit and to the exclusion of the terminal ileum caused by the covering ileostomy.