A circulating biomarker risk-prediction model correlates with CHADS-2 risk score in chronic atrial fibrillation

AbstractBackgroundInflammation and oxidative stress have been linked to the origin and persistence of atrial fibrillation (AF). CHADS-2 scoring system is a risk stratification schema well validated in prognostication of stroke in AF. We evaluated the association of markers of oxidative stress and inflammation with CHADS-2 scores in chronic AF patients.MethodsCHADS-2 scores were calculated for 64 subjects with chronic AF. Serum markers of inflammation [C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α)] and of oxidative stress [derivatives of reactive oxygen metabolites (DROMs) and isoprostanes (IsoPs)] were measured.ResultsTwenty subjects were categorized as 0 (no risk), 24 as 1 (intermediate risk) and 20 as 2 (severe risk) based on their CHADS-2 scores. High sensitivity-CRP (CHADS-2 0=40.0%, 1=70.0%, 2=90.0%; p=0.003) and DROMs (CHADS-2 0=45%, 1=78%, 2=80%; p=0.04) were positively associated with the CHADS-2 risk score. Subjects with intermediate to severe CHADS-2 risk retained significant associations with abnormal hs-CRP (OR: 5.3, 95%CI: 1.1–25.0) and DROMs (adjusted OR: 6.7, 95%CI: 1.2–38.8) after adjusting for gender and hypertension. In a multiple logistic interaction model, there was no significant interaction between hs-CRP and DROMs in their association with CHADS-2 risk categories (p=0.64). A biomarker risk-model, combining hs-CRP and DROMs, correlated well with the CHADS-2 risk categories (r=0.49, p<0.001).ConclusionsA biomarker risk-model using a combination of hs-CRP and DROMs correlates well with CHADS-2 risk scores in chronic AF. Either or both of these markers may add predictive power to future stroke risk prediction models

A novel mutation in the ABCA1 gene causing an atypical phenotype of tangier disease

Tangier disease is a rare autosomal-recessive disorder caused by mutation in the ATP binding cassette transporter 1 (ABCA1) gene. Typically, Tangier disease manifests with symptoms and signs resulting from the deposition of cholesteryl esters in nonadipose tissues; chiefly, in peripheral nerves leading to neuropathy and in reticulo-endothelial organs, such as liver, spleen, lymph nodes, and tonsils, causing their enlargement and discoloration. An association with early cardiovascular disease can be variable. We describe a patient with a unique phenotype of Tangier disease from a novel splice site mutation in the ABCA1 gene that is associated with a central nervous system presentation resembling multiple sclerosis, and the presence of premature atherosclerosis

The effect of lipid modification on peripheral artery disease after endovascular intervention trial (ELIMIT)

Methods: A total of 102 patients were randomized to either mono-therapy with simvastatin (40 mg daily) or triple-therapy with simvastatin (40 mg daily), extended-release niacin (1500 mg daily), and ezetimibe (10 mg daily). MRI was performed at baseline and 6, 12, and 24 months. SFA wall, lumen, and total vessel volumes were quantified. MRI-derived SFA parameters and lipids were analyzed with multilevel models and nonparametric tests, respectively.Results: Baseline characteristics did not differ between mono and triple-therapy groups, except for ethnicity (p = 0.02). SFA wall, lumen, and total vessel volumes increased non-significantly for both groups between baseline and 24-months. Non-high-density lipoprotein cholesterol was significantly reduced at 12 months with triple-therapy compared with mono-therapy (p = 0.01).Conclusion: No significant differences were observed between mono-therapy using simvastatin and triple-therapy with simvastatin, extended-release niacin, and ezetimibe for 24-month changes in SFA wall, lumen, and total vessel volumes.Clinical trial registration information: NCT00687076; Link: http://clinicaltrials.gov/ct2/show/NCT00687076

Non-high-density lipoprotein cholesterol calculation and goal awareness among physicians-in-training

Background: Non-high density lipoprotein cholesterol (non-HDL-C) goal attainment per Adult Treatment Panel III (ATP III) guidelines remains low.Objective: To understand gaps in knowledge and practices of physicians-in-training (internal medicine, family medicine, cardiology, endocrinology) towards non-HDL-C.Methods: A survey based on a conceptual model to assess the trainee\u27s knowledge, attitudes, and practice regarding non-HDL-C was developed and administered to physicians-in-training (n = 655) at 26 training programs in the United States. Responses of those in internal medicine and family medicine (residents-in-training; n = 418) were compared with those in cardiology and endocrinology (fellows-in-training; n = 124).Results: Response rate was 83.7%. Fifty-three percent of residents and 31% of fellows-in-training had not read the ATP III guidelines (P \u3c .001). Thirty-three percent of the residents and 35% fellows-in-training could not calculate non-HDL-C from a standard lipid panel (P = .7). Sixty-seven percent of the residents and 52% of fellows were not aware of treatment goals for non-HDL-C (P = .004 for comparison between residents and fellows). Both residents and fellows reported infrequent calculation of non-HDL-C levels in patients with elevated triglycerides (≥200 mg/dL; 32.5% vs 35.4%, respectively, P = .6). Lack of familiarity with ATP III guidelines, lack of knowledge regarding importance of non-HDL-C, lack of institutional mandate to calculate non-HDL-C, and lack of emphasis on non-HDL-C by teaching staff were reported as barriers to non-HDL-C use in routine clinical practice.Conclusions: At least one-third of physicians-in-training could not calculate non-HDL-C from a standard lipid panel, and a large number were not aware of ATP III treatment goals pertaining to non-HDL-C. This area represents one for improvement if non-HDL-C is to be retained as a treatment target in the forthcoming ATP-IV guidelines

Renin-Angiotensin Activation and Oxidative Stress in Early Heart Failure with Preserved Ejection Fraction

Animal models have suggested a role of renin-angiotensin system (RAS) activation and subsequent cardiac oxidation in heart failure with preserved ejection fraction (HFpEF). Nevertheless, RAS blockade has failed to show efficacy in treatment of HFpEF. We evaluated the role of RAS activation and subsequent systemic oxidation in HFpEF. Oxidative stress markers were compared in 50 subjects with and without early HFpEF. Derivatives of reactive oxidative metabolites (DROMs), F2-isoprostanes (IsoPs), and ratios of oxidized to reduced glutathione (Eh GSH) and cysteine (Eh CyS) were measured. Angiotensin converting enzyme (ACE) levels and activity were measured. On univariate analysis, HFpEF was associated with male sex (p=0.04), higher body mass index (BMI) (p=0.003), less oxidized Eh CyS (p=0.001), lower DROMs (p=0.02), and lower IsoP (p=0.03). Higher BMI (OR: 1.3; 95% CI: 1.1–1.6) and less oxidized Eh CyS (OR: 1.2; 95% CI: 1.1–1.4) maintained associations with HFpEF on multivariate analysis. Though ACE levels were higher in early HFpEF (OR: 1.09; 95% CI: 1.01–1.05), ACE activity was similar to that in controls. HFpEF is not associated with significant systemic RAS activation or oxidative stress. This may explain the failure of RAS inhibitors to alter outcomes in HFpEF