Hypertension and diabetes significantly enhance the risk of cardiovascular disease in patients with psoriatic arthritis.

OBJECTIVES: New evidence has lightened the linkage between psoriatic arthritis (PsA) and the development of atherosclerosis and cardiovascular disease (CVD). We aimed to describe the prevalence of cardiovascular events and associated risk factors among patients with PsA. METHODS: Retrospective evaluation of medical records from consecutive PsA patients who fulfilled the CASPAR criteria for PsA attending a specialised spondyloarthritis clinic at a single referral centre. CVD was defined based on the occurrence of coronary artery disease (CAD) or cerebrovascular ischaemic disease events. RESULTS: We evaluated 158 PsA patients, 48.7% females and 51.3% males, aged 53.7±13.9 yrs. Mean PsA duration was 13.7±8.9 yrs and polyarticular subtype affected 66 (42%) patients. According to drug therapy, 85 (54%) were using NSAIDs and 21 (13%) low-dose prednisone; 32 (20%) were on anti-TNF agents, 94 (60%) metothrexate, 18 (11%) leflunomide, 13 (8%) sulfasalazine, 5 (3%) other immunossupressors and 4 (2.5%) were on chloroquine. Over half patients (87, 55%) had arterial hypertension (AH); 51 (32%) had dyslipidaemia (DLP), 38 (29%) hypertriglyceridemia and 36 (23%) diabetes mellitus (DM). Lipid profile was similar for both genders with mean total cholesterol= 186.5±38.6mg/dl, LDL=112.3±30.6 mg/dl, HDL= 47.89±14.6 and triglycerides= 127.4± 65.6 mg/dl. Of note, 14% PsA patients have had CVD, namely cerebrovascular or coronary heart disease. Sex, age, disease duration, joint involvement subtype, disease activity, CRP and lipid levels were similar among patients with and without CVD. The prevalence of AH (95% vs. 45%, p<0.001), DLP (75% vs. 27.7%, p<0.001) and DM (60% vs. 19%, p<0.001) were significantly greater in PsA patients who have had CVD compared to those without CVD, conferring an odds ratio of 21.0 for AH and of 5.4 for DM. CONCLUSIONS: The high prevalence of CVD in PsA patients is influenced by increased AH and DM. Hence early recognition and specific treatment is mandatory in order to reduce the risk for CVD, avoiding early morbidity and mortality.

ACE gene titration in mice uncovers a new mechanism for ACE on the control of body weight.

Mice harboring 1, 2, or 3 copies of the angiotensin-converting enzyme (ACE) gene were used to evaluate the quantitative role of the ACE locus on obesity. Three-copy mice fed with a high-fat diet had lower body weight and peri-epididymal adipose tissue than did 1- and 2-copy mice (P < 0.05). On regular diet, 3-copy mice had to eat more to maintain the same body weight; on a high-fat diet, they ate the same but weighed less than 1- and 2-copy mice (P < 0.05), indicating a higher metabolic rate in 3-copy mice that was not affected by ANG II AT(1) blocker treatment. A catalytically inactive form of thimet oligopeptidase (EC 3.4.24.15; EP24.15) was used to isolate ACE substrates from adipose tissue. Liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) identified 162 peptide peaks; 16 peptides were present in both groups (1- and 3-copy mice fed with a high-fat diet), whereas 58 of the 72 unique peptides were found only in the 3-copy mice. Peptide size distribution was shifted to lower molecular weight in 3-copy mice. Two of the identified peptides, LVVYPWTQRY and VVYPWTQRY, which are ACE substrates, inhibited in vitro protein kinase C phosphorylation in a concentration-dependent manner. In addition, neurolysin (EC 3.4.24.16; EP24.16) activity was lower in fat tissue from 3- vs. 1-copy mice (P < 0.05). Taken together, these results provide evidence that ACE is associated with body weight and peri-epididymal fat accumulation. This response may involve the generation of oligopeptides that inhibit the activity of EP24.16 and other oligopeptidases within the adipose tissue.