Mao Shin Lin

Serum Vascular Adhesion Protein-1 Predicts 10-Year Cardiovascular and Cancer Mortality in Individuals With Type 2 Diabetes

OBJECTIVE Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the breakdown of amines to produce aldehyde, hydrogen peroxide, and ammonia. Serum VAP-1 correlates positively with both acute hyperglycemia and diabetes. We conducted a cohort study to evaluate whether serum VAP-1 predicts 10-year survival in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Between July 1996 and June 2003, we enrolled 661 type 2 diabetic subjects at National Taiwan University Hospital. Serum VAP-1 in the samples obtained at enrollment was measured by time-resolved immunofluorometric assay. The vital status of all subjects was ascertained by linking their data with computerized death certificates in Taiwan. RESULTS The medium follow-up period was 10.4 years. Subjects with serum VAP-1 in the highest tertile had a hazard ratio (HR) of 2.19 (95% CI 1.17–4.11) for all-cause mortality adjusted for age, sex, smoking, history of cardiovascular disease, obesity, hypertension, hemoglobin A1c, diabetes duration, total cholesterol, use of statins, abnormal ankle-brachial index, estimated glomerular filtration rate (eGFR), and proteinuria. The adjusted HRs for logarithmically transformed serum VAP-1 were 5.83 (95% CI 1.17–28.97) for cardiovascular mortality, 6.32 (95% CI 1.25–32.00) for mortality from cardiovascular and diabetic causes, and 17.24 (95% CI 4.57–65.07) for cancer mortality. There were four variables, including age, serum VAP-1, proteinuria, and eGFR, which could enhance mortality prediction significantly. CONCLUSIONS Serum VAP-1 can predict 10-year all-cause mortality, cardiovascular mortality, and cancer mortality independently in type 2 diabetic subjects. Serum VAP-1 is a novel biomarker that improves risk prediction over and above established risk factors.

Serum vascular adhesion protein-1 is increased in acute and chronic hyperglycemia

BACKGROUNDnThe relationship between serum vascular adhesion protein-1 (VAP-1) and plasma glucose in normal and drug-naïve type 2 diabetes subjects is unclear. We examined if serum VAP-1 changed acutely to oral glucose loading and analyzed the relationship between serum VAP-1, fasting plasma glucose (FPG), hemoglobin A1c, and type 2 diabetes.nnnMETHODSnAdults without history of diabetes were included. Subjects taking anti-diabetic drugs were excluded. Serum VAP-1 was analyzed by time-resolved immunofluorometric assay.nnnRESULTSnWe recruited 333 subjects (186 females and 147 males), aged 56.1 +/- 11.6 y. After glucose challenge, serum VAP-1 rose significantly at 30 min (p < 0.0001) and lasted until 2 h (p < 0.0001). The change of serum VAP-1 between fasting and 30-min postload correlated inversely to the change of plasma insulin (r = -0.21, p = 0.049). Fasting serum VAP-1 was associated with FPG in those with FPG > or = 5.55 mmol/l (p = 0.025) but not in those with FPG < 5.55 mmol/l (p = NS). Fasting serum VAP-1 were higher in diabetic subjects (p = 0.04) and correlated positively to hemoglobin A1c (r = 0.18, p = 0.002) after adjusting for age, gender, and waist circumference.nnnCONCLUSIONSnSerum VAP-1 is increased in both acute and chronic hyperglycemia. Whether serum VAP-1 is a good biomarker for hyperglycemia-associated complications merits further investigation.

Serum vascular adhesion protein-1 is higher in subjects with early stages of chronic kidney disease

OBJECTIVESnAn increased level of serum vascular adhesion protein-1 (VAP-1) has been found in patients with diabetes mellitus and vascular disorders. This study examined whether serum VAP-1 levels are associated with chronic kidney disease (CKD).nnnDESIGN AND METHODSnWe included 262 subjects aged 30 and above with fasting plasma glucose level <7 mmol/L checked within 1 year. First morning urine specimens were collected. Microalbuminuria was defined if urinary albumin-to-creatinine ratio > or =30 microg/mg creatinine. The glomerular filtration rate (GFR) was estimated. CKD stages were defined according to the suggestions of the National Kidney Foundation. Serum VAP-1 levels were analyzed by immunofluorometric assay.nnnRESULTSnSerum VAP-1 levels were positively associated with the urinary albumin-to-creatinine ratio (r=0.29, p<0.0001) and negatively associated with estimated GFR (r=-0.24, p=0.0001). Subjects with CKD stage 2 (N=51) and stage 3 (N=91) had significantly higher levels of serum VAP-1 than those without CKD (p=0.0003 and p=0.035, adjusted for age and gender, respectively). A high serum VAP-1 level was associated with the presence of CKD (OR 1.63 for 1 SD increase of VAP-1, p=0.018), adjusting for age, sex, and smoking. Ordered logit models revealed that high serum VAP-1 levels correlated with advanced stages of CKD.nnnCONCLUSIONSnSerum levels of VAP-1 are associated with the severity of kidney damage or stages of kidney disease. The true mechanism which links the serum VAP-1 and CKD remains to be elucidated in further studies.

Procedural Safety and Potential Vascular Complication of Endovascular Recanalization for Chronic Cervical Internal Carotid Artery Occlusion

Background—Patients with chronic cervical internal carotid artery occlusion (ICAO) and cerebral ischemia may benefit from revascularization. The feasibility of endovascular recanalization for chronic ICAO has been reported recently, but its safety is still unproven. We report the follow-up results of 54 chronic ICAO patients who underwent endovascular recanalization, focusing on potential vascular complications and corresponding management. Methods and Results—Endovascular recanalization for chronic ICAO was attempted in 54 consecutive patients (48 men; 69.2±9.8 years old) with either recurrent neurological deficit or objective ipsilateral hemisphere ischemia. Mean duration from occlusion documentation to the procedure was 237±327 days (range, 56 to 1424 days). Adverse events while in the hospital and during the 3-month follow-up were recorded. Successful recanalization was achieved in 35 of 54 patients (65%). Three-month cumulative stroke and death rate was 4% (2 of 54), including 1 in-hospital fatal nonipsilateral stroke and 1 in-hospital minor ipsilateral stroke secondary to systemic hypotension. Vascular complications developed in 3 of 54 patients (6%), including 1 late pseudoaneurysm formation 3 months after recanalization, 1 immediate carotid-cavernous fistula after recanalization, and 1 minor extravasation at carotid bifurcation after failed recanalization. However, no clinical sequela was noted with close follow-up and adequate management. Conclusion—Certain immediate or delayed vascular complications may develop during or after the endovascular recanalization for chronic ICAO. Although periprocedural death and stroke rate is limited in our study, further study combining neuroimaging tools and cognitive function evaluation is mandatory to assess its utility and appropriateness in patients with chronic ICAO.

Time-dependent benefit of initial thrombosuction on myocardial reperfusion in primary percutaneous coronary intervention

Background:u2002 In ST‐segment elevation acute myocardial infarction (STEMI), dislodgement of thrombus within the culprit artery during primary percutaneous coronary intervention (PCI) may cause distal embolisation and impaired myocardial reperfusion. Clinical results of thromboembolic protection strategies have been controversial. We conducted this study to investigate whether the benefit of thrombus removal is time dependent.

Change of serum vascular adhesion protein-1 after glucose loading correlates to carotid intima-medial thickness in non-diabetic subjects.

BACKGROUNDnWe investigated if serum vascular adhesion protein-1 (SSAO/VAP-1) changed acutely following oral glucose loading and whether such changes are correlated with surrogate markers of atherosclerosis.nnnMETHODSnA total of 115 non-diabetics subjects were enrolled for an oral glucose tolerance test (OGTT). Carotid intima-medial thickness (IMT) was measured by ultrasonography. Serum SSAO/VAP-1 was analyzed by time-resolved immunofluorometric assay. Serum thiobarbituric acid reactive substances (TBARS) and advanced glycated end products (AGEs) were measured by fluorometric assays.nnnRESULTSnSerum SSAO/VAP-1 increased significantly at 30 min after oral glucose loading and lasted to 2 h (p=0.0005 and p<0.0001, for 30 min and 2 h respectively). The area under curve of serum SSAO/VAP-1 during OGTT (AUC-VAP-1) correlated significantly with carotid IMT, independent of age, gender, low-density lipoprotein cholesterol, systolic blood pressure, hemoglobin A1c, serum TBARS, AGEs, and high-sensitivity C-reactive protein. Subjects with a positive AUC-VAP-1 had significantly higher serum TBARS and AGEs than subjects with a negative AUC-VAP-1 adjusted for age and gender.nnnCONCLUSIONSnSerum SSAO/VAP-1 changed acutely following oral glucose loading in non-diabetic subjects. Change of serum SSAO/VAP-1 correlated independently to serum TBARS, AGEs, and carotid IMT. Our findings suggest that acute change of serum SSAO/VAP-1 is a novel marker for hyperglycemia-induced atherosclerosis.

Plasma apelin: A novel biomarker for predicting diabetes

BACKGROUNDnApelin regulates insulin sensitivity and secretion in animals. However, whether plasma apelin predicts incident diabetes in humans remains unknown.nnnMETHODSnWe studied a cohort including 447 subjects (148 men, 299 women) without diabetes and followed for an average of 3y. Diabetes was diagnosed by an oral glucose tolerance test, plasma hemoglobin A1c, and if the subject was taking medications for diabetes. Plasma apelin-12 at baseline was measured with a commercial kit.nnnRESULTSnPlasma apelin concentrations were higher in women than in men at baseline (p=0.007). During follow-up, 43 subjects developed type 2 diabetes. Higher plasma apelin concentrations were associated with a higher risk of diabetes in men (p=0.049) but not in women. Plasma apelin predicted incident type 2 diabetes in men (hazard ratio, 2.13, 95% CI 1.29-3.51, p<0.05), but not in women, adjusted for age, family history of diabetes, hemoglobin A1c, body mass index, hypertension, and HOMA2-IR. Apelin could improve the prediction ability beyond traditional risk factors in men, and the sensitivity and specificity of plasma apelin at 0.9ng/ml for this prediction were 63.2% and 58.9%, respectively. In men at risk for diabetes (HbA1c 5.7-6.4%, FPG 100-125mg/dl, or OGTT-2h-PG 140-199mg/dl), the risk for developing diabetes was higher in those with higher plasma apelin concentration than in those with lower plasma apelin concentrations (10.6%/year vs. 5.1%/year, p<0.001).nnnCONCLUSIONSnPlasma apelin is a novel biomarker for predicting type 2 diabetes in men.

Association of the Recovery of Objective Abnormal Cerebral Perfusion With Neurocognitive Improvement After Carotid Revascularization

OBJECTIVESnThis study sought to report the effect of carotid artery stenting (CS) on neurocognitive function (NCF) in patients with severe carotid artery occlusive disease, depending on baseline brain perfusion status.nnnBACKGROUNDnThe effect of CS on NCF has been controversial.nnnMETHODSnWe prospectively enrolled 61 patients with carotid artery disease (22 with occlusion, 39 with severe stenosis) in whom CS was attempted. Computed tomography perfusion and NCF assessments including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog), verbal fluency, and Color Trails Test Parts 1 and 2 were applied before and 3 months after intervention.nnnRESULTSnSuccessful recanalization was achieved in 14 of 22 occlusion patients (64%) and in all 39 severe stenosis patients. Two cases were excluded due to procedural cerebral complications. The patients were divided into 3 groups: group 1 (nxa0= 8) consisted of patients with abnormal baseline ipsilateral cerebral perfusion in whom CS failed; group 2 (nxa0=xa033) consisted of patients with abnormal baseline ipsilateral cerebral perfusion in whom CS was successful; andxa0group 3 (nxa0= 19) consisted of patients without abnormal baseline ipsilateral cerebral perfusion in whom CS was successful. The demographics and baseline NCF were similar among groups. Only in group 2 was there significant improvement in ADAS-Cog (pre-procedure median [interquartile range]: 6 [4 to 9] vs. post-procedure: 5 [3 to 7], pxa0=xa00.002), MMSE (pre-procedure: 27 [25 to 28] vs. post-procedure: 28 [25 to 29], pxa0= 0.004) and Color Trails Test Part 1 (pre-procedure: 100 [78.5 to 136.5] s vs. post-procedure: 97 [60 to 128.5] s, pxa0= 0.003) after CS. Significant difference in changes from baseline was observed only in the Color Trails Test Part 1 among groups (group 1 vs. 2xa0vs. 3: 1.5 [-14 to 11.5] vs.xa0-12.5 [-36.5 to 0.5] vs.xa0-0.5 [-11 to 27], pxa0= 0.0159). Significant correlation between the change of ipsilateral brain perfusion and MMSE (rxa0=xa0-0.33, pxa0= 0.01) was also identified.nnnCONCLUSIONSnSuccessful CS for severe carotid stenosis/occlusion improves NCF, but only in patients with objective baseline abnormal cerebral perfusion.

Clinical Outcomes Following Transcatheter Aortic Valve Replacement in Asian Population

OBJECTIVESnThis study describes the characteristics of a real-world Asian patient population treated with transcatheter aortic valve replacement (TAVR) and evaluates their clinical outcomes.nnnBACKGROUNDnNo previously reported randomized or observational studies adequately assess the safety and efficacy of TAVR in an Asian population.nnnMETHODSnThe Asian TAVR registry is an international multicenter study that enrolled patients with aortic stenosis who underwent TAVR in Asian countries.nnnRESULTSnIn total, 848 patients with mean STS score of 5.2 ± 3.8% were enrolled between March 2010 and September 2014 at 11 centers in 5 countries. The Edwards Sapien or Medtronic CoreValve was implanted in 64.7% and 35.3% of patients, respectively. The procedural success rate was 97.5%. The 30-day and 1-year mortality rates were 2.5% and 10.8%, respectively. There was no difference in 1-year mortality between devices (Sapien: 9.4%; CoreValve: 12.2%; log-rank pxa0= 0.40). The rates of stroke, life-threatening bleeding, major vascular complications and acute kidney injury (stage 2 to 3) were 3.8%, 6.4%, 5.0% and 3.3%, respectively. Moderate or severe paravalvular leakage was significantly more common with the CoreValve than Sapien (14.4% vs. 7.3%; pxa0= 0.001). According to the multivariate model, a higher STS score, lower body mass index, New York Heart Association functional class III-IV symptoms, diabetes mellitus, prior cerebrovascular accident, low mean gradient at baseline, and moderate or severe paravalvular leakage were significantly associated with reduced survival.nnnCONCLUSIONSnDespite anatomical features of concern, the clinical outcomes of TAVR in our Asian population werexa0favorable in comparison with those of previously published trials and observational studies. (The Asian Transcatheter Aortic Valve Replacement Registry [Asian TAVR]; NCT02308150).

Metabolic syndrome defined by IDF and AHA/NHLBI correlates better to carotid intima-media thickness than that defined by NCEP ATP III and WHO.

AIMSnWe conducted this study to compare the relationships between subclinical atherosclerosis and metabolic syndrome (MS) defined by four definitions in Chinese subjects.nnnMETHODSnIn 2006-2007, we enrolled 140 Chinese subjects without reported diabetes in this study. Anthropometric, biochemical profile, and carotid intima-media thickness (IMT) were measured. MS was defined by International Diabetes Federation (IDF), American Heart Association and the National Heart, Lung, and Blood Institute (AHA/NHLBI), National Cholesterol Education Program Adult Treatment Panal III (NCEP-ATP III), and World Health Organization (WHO) criteria.nnnRESULTSnSubjects with MS defined by IDF and AHA/NHLBI criteria had significantly higher carotid IMT, controlling for age, gender, smoking, and serum LDL-C (MS by IDF, partial r=0.225, p=0.008; AHA/NHLBI, partial r=0.176, p=0.04). The association between carotid IMT and MS defined by NCEP-ATP III or WHO criteria was not significant. Subjects with more components of MS defined by IDF, AHA/NHLBI, or NCEP-ATP III criteria correlated to higher carotid IMT in adjusted models (p-values for trend, MS by IDF, 0.011; AHA/NHLBI, 0.011; NCEP-ATPIII, 0.01; WHO, 0.113).nnnCONCLUSIONnMS definitions by IDF and AHA/NHLBI criteria are the best among four definitions in detecting subclinical atherosclerosis in non-diabetic Chinese subjects; whereas MS defined by WHO criteria is the worst.