Is There a Sex-Related Difference in the Obesity Paradox in Systolic Heart Failure? Sex-Related Difference in the Obesity Paradox.

PURPOSE: Obesity is often associated with better clinical outcomes in heart failure (HF). This so-called obesity paradox remains controversial. The aim of present study was to investigate the prognostic value of obesity in patients hospitalized for systolic HF. MATERIALS AND METHODS: We performed a pooled analysis of data from two multicenter, observational HF studies. Patients hospitalized for systolic HF were eligible for the present study. We divided the subjects into two groups, a normal body mass index (BMI) group and a high BMI group. Study endpoints included all-cause mortality and any re-hospitalization within 1 year. RESULTS: We enrolled 3145 patients (male, 1824; female, 1321). The high BMI group was significantly associated with lower 1-year mortality rate [odds ratio (OR), 0.543; 95% confidence interval (CI), 0.355-0.832] after adjusting for age, hypertension, diabetes, ischemic HF, previous myocardial infarction, serum creatinine level, anemia, and ejection fraction in men. After adjustment for clinical characteristics, high BMI was not significantly associated with 1-year mortality (OR, 0.739; 95% CI, 0.450-1.216) or 1-year re-hospitalization (OR, 0.958; 95% CI, 0.696-1.319) in women. CONCLUSION: In pooled analysis of data from two Korean HF registries, the high BMI group was independently associated with lower 1-year mortality rate from systolic HF, especially in men.

Efficacy of combination treatment with intracoronary abciximab and aspiration thrombectomy on myocardial perfusion in patients with ST-segment elevation myocardial infarction undergoing primary coronary stenting.

PURPOSE: We aimed to investigate whether combination therapy using intracoronary (IC) abciximab and aspiration thrombectomy (AT) enhances myocardial perfusion compared to each treatment alone in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). MATERIALS AND METHODS: We enrolled 40 patients with STEMI, who presented within 6 h of symptom onset and had Thrombolysis in MI flow 0/1 or a large angiographic thrombus burden (grade 3/4). Patients were randomly divided into 3 groups: 10 patients who received a bolus of IC abciximab (0.25 mg/kg); 10 patients who received only AT; and 20 patients who received both treatments. The index of microcirculatory resistance (IMR) was measured with a pressure sensor/thermistor-tipped guidewire following successful PCI. Microvascular obstruction (MVO) was assessed using cardiac magnetic resonance imaging on day 5. RESULTS: IMR was lower in the combination group than in the IC abciximab group (23.5±7.4 U vs. 66.9±48.7 U, p=0.001) and tended to be lower than in the AT group, with barely missed significance (23.5±7.4 U vs. 37.2±26.1 U, p=0.07). MVO was observed less frequently in the combination group than in the IC abciximab group (18.8% vs. 88.9%, p=0.002) and tended to occur less frequently than in the AT group (18.8% vs. 66.7%, p=0.054). No difference of IMR and MVO was found between the IC abciximab and the AT group (66.9±48.7 U vs. 37.2±26.1 U, p=0.451 for IMR; 88.9% vs. 66.7%, p=0.525 for MVO, respectively). CONCLUSION: Combination treatment using IC abciximab and AT may synergistically improve myocardial perfusion in patients with STEMI undergoing primary PCI (Trial Registration: clinicaltrials. gov Identifier: NCT01404507).

A prospective study of epicardial adipose tissue and incident metabolic syndrome: the ARIRANG study.

Increased epicardial adipose tissue (EAT) may be closely associated with the development of metabolic abnormalities. We investigated whether EAT predicts the incident metabolic syndrome in a community-based, middle-aged population. The study subjects were comprised of 354 adults (134 men and 220 women) aged 40 to 70 yr without metabolic syndrome. Baseline EAT thickness, measured by echocardiography, was compared between subjects who developed new-onset metabolic syndrome at follow-up survey and those who did not. After an average of 2.2 yr of follow-up, 32 men (23.9%) and 37 women (16.8%) developed metabolic syndrome. Median EAT thickness at baseline was significantly higher in male subjects who developed metabolic syndrome than those who did not (1.52 mm vs 2.37 mm, P<0.001). The highest quartile of EAT thickness (≥2.55 mm) was associated with increased risk of progression to metabolic syndrome (Odds ratio [OR], 3.09; 95% confidence interval [CI], 1.11-8.66) after adjustment for age, smoking, alcohol intake, regular exercise, total energy intake, high sensitive C-reactive protein and homeostasis model assessment of insulin resistance in men. A significant association of EAT with incident metabolic syndrome was not seen in women (OR, 1.25; 95% CI, 0.54-2.90). In conclusion, increased EAT thickness is an independent predictor for incident metabolic syndrome in men.

Genotype- and Phenotype-Directed Personalization of Antiplatelet Treatment in Patients with Non-ST Elevation Acute Coronary Syndromes Undergoing Coronary Stenting.

BACKGROUND AND OBJECTIVES: We evaluated the effectiveness of genotype- and phenotype-directed individualization of P2Y12 inhibitors to decrease high on-treatment platelet reactivity (HOPR). SUBJECTS AND METHODS: Sixty-five patients undergoing percutaneous coronary intervention for non-ST elevation acute coronary syndromes were randomly assigned to genotype- or phenotype-directed treatment. All patients were screened for CYP2C19(*)2, (*)3, or (*)17 alleles by using the Verigene CLO assay (Nanosphere, Northbrook, IL, USA). The P2Y12 reaction unit (PRU) was measured using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA). 21 CYP2C19 (*)2 or (*)3 carriers (65.6%) and 11 patients with HOPR (33.3%), defined as a PRU value ≥230, were given 90 mg ticagrelor twice daily; non-carriers and patients without HOPR were given 75 mg clopidogrel daily. The primary endpoint was the percentage of patients with HOPR after 30 days of treatment. RESULTS: PRU decreased following both genotype- and phenotype-directed therapies (242±83 vs. 109±90, p<0.001 in the genotype-directed group; 216±74 vs. 109±90, p=0.001 in the phenotype-directed group). Five subjects (16.2%) in the genotype-directed group and one (3.3%) in the phenotype-directed group had HOPR at day 30 (p=0.086). All patients with HOPR at the baseline who received ticagrelor had a PRU value of <230 after 30 days of treatment. Conversely, clopidogrel did not lower the number of patients with HOPR at the baseline. CONCLUSION: Tailored antiplatelet therapy according to point-of-care genetic and phenotypic testing may be effective in decreasing HOPR after 30 days.

Intravascular ultrasound-guided percutaneous coronary intervention improves the clinical outcome in patients undergoing multiple overlapping drug-eluting stents implantation.

BACKGROUND AND OBJECTIVES: Stented segment length is a predictive factor for restenosis and stent thrombosis still in the drug-eluting stent (DES) era, and the benefit of routine intravascular ultrasound (IVUS) is still unclear. The aim of the present study was to investigate whether IVUS-guided percutaneous coronary intervention (PCI) improved the vascular outcomes as compared with conventional PCI in the treatment of diffuse coronary artery disease. SUBJECTS AND METHODS: From our registry database from January 2006 to May 2009, we identified 85 consecutive patients with de novo coronary lesions treated with at least 64 mm of multiple, overlapping DES. The 2-year rate of major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, non-fatal myocardial infarction, target lesion revascularization (TLR), or stent thrombosis, was compared according to the use of IVUS. RESULTS: The 2-year MACE rate was lower in the IVUS-guided group than that of the angiography-guided group (8% vs. 33.3%, p=0.005). The incidence of TLR was lower in patients with IVUS use than in those without IVUS use (0% vs. 27.8%, p<0.001). On Cox proportional hazard analysis, no IVUS use {hazard ratio (HR) 5.917, 95% confidence interval (CI) 1.037-33.770, p=0.045} and age (HR 1.097, 95% CI 1.006-1.138, p=0.032) were unfavorable predictors for the 2-year MACE. CONCLUSION: The use of IVUS may improve the effectiveness and safety of multiple overlapping drug-eluting stenting for long, diffuse coronary lesions.

Fragmented QRS complexes are not hallmarks of myocardial injury as detected by cardiac magnetic resonance imaging in patients with acute myocardial infarction.

BACKGROUND: Q waves on a 12-lead electrocardiography (ECG) are considered to be classic hallmarks of prior myocardial infarction. However, one study suggested that the fragmented QRS complex (fQRS) on ECG is a highly sensitive and specific marker of myocardial scarring on a nuclear stress test. The study aimed to investigate the diagnostic accuracy of fragmented QRS complexes compared with Q waves for myocardial injury detected by delayed contrast-enhanced cardiovascular magnetic resonance imaging (DE-CMRI) in subjects with acute myocardial infarction. METHODS: Electrocardiograms of 190 subjects with myocardial infarction who underwent DE-CMR were analyzed. fQRS was defined by the presence of an additional R wave (R″), or notching of the S wave, or more than one R' in two contiguous leads. RESULTS: Delayed enhancement was observed in 180 (94.7%) patients. Transmural enhancement was noted in 78 (43.3%) and subendocardial enhancement in 102 (56.7%) patients. The sensitivity and specificity of Q waved and fQRS for diagnosing delayed enhancement were 59.4% vs. 66.7% and 90.0% vs. 40.0%. The area under the receiver-operator characteristics curve of delayed enhancement was 0.75 for Q waves and 0.53 for fQRS (p=0.04). The areas under the ROC curves of the transmurality of delayed enhancement were 0.44 for fQRS and 0.58 for Q waves (p=0.73). CONCLUSIONS: fQRS has poor accuracy for the detection of myocardial injury compared with Q waves. fQRS and Q waves are not valuable tools for the diagnosis transmural irreversible myocardial injury in acute myocardial infarction.

Prospective study of serum adiponectin and incident metabolic syndrome: the ARIRANG study.

OBJECTIVE: Increased adiponectin levels may play a protective role in the development of metabolic abnormalities, but prospective studies of the predictive value of serum adiponectin to identify individuals at high risk of new-onset metabolic syndrome are lacking. We investigated whether serum adiponectin predicts incident cases of the metabolic syndrome in a population-based longitudinal study. RESEARCH DESIGN AND METHODS: A prospective cohort study was conducted of 2,044 adults (831 men and 1,213 women) aged 40-70 years without metabolic syndrome examined in 2005-2008 (baseline) and 2008-2011 (follow-up). Baseline serum adiponectin concentrations were measured by radioimmunoassay. RESULTS: During an average of 2.6 years of follow-up, 153 men (18.4%) and 199 women (16.4%) developed metabolic syndrome. In multivariable-adjusted models, the odds ratio for incident metabolic syndrome comparing the highest with the lowest quartiles of adiponectin levels was 0.25 (95% CI 0.14-0.47) in men and 0.45 (0.28-0.74) in women. While serum adiponectin did not improve the area under the ROC curve for predicting new-onset metabolic syndrome based on information from metabolic syndrome components, the net reclassification improvement and the integrated discrimination improvement of prediction models including adiponectin were significantly higher compared with those of models not including adiponectin among men, with a significant difference between men and women (P = 0.001). CONCLUSIONS: Increased adiponectin is an independent protective factor for incident metabolic syndrome in men and women, and it may have a clinical role in predicting new-onset metabolic syndrome among men.

Urinary levels of 8-iso-prostaglandin f2α and 8-hydroxydeoxyguanine as markers of oxidative stress in patients with coronary artery disease.

BACKGROUND AND OBJECTIVES: The objective of this study was to determine if urinary levels of 8-iso-prostaglandin F2α (8-iso-PGF2α) and 8-hydroxydeoxyguanine (8-OHdG) could be used as markers of the oxidative stress in significant coronary artery disease (CAD). SUBJECTS AND METHODS: We conducted a case-control study in 104 subjects assessed by coronary angiography with the following diagnoses: 35 consecutive cases of significant CAD and 69 cases of non-CAD with stable angina. We compared the urinary levels of 8-iso-PGF 2α and 8-OHdG, as measured by immunoassay between the 2 groups. RESULTS: History of hypertension was significantly higher and high density lipoprotein-cholesterol level significantly lower in the CAD group compared with those in the non-CAD group. Median levels of 8-iso-PGF2α were significantly higher in the CAD group compared with the non-CAD group (9.2 vs. 6.0 ng/mg, p=0.001). There were no significant differences in 8-OHdG values between the 2 groups. The odds ratio of 8-iso-PGF2α for CAD in the highest tertile compared with that in the lowest tertile was 7.39 (95% confidence interval; 1.71-31.91). There was no significant difference in median values of 8-iso-PGF2α between single- and multi-vessel CAD. CONCLUSION: Urinary 8-iso-PGF 2α was independently associated with significant CAD in this case-control study.

Different prognostic significance of high on-treatment platelet reactivity as assessed by the VerifyNow P2Y12 assay after coronary stenting in patients with and without acute myocardial infarction.

OBJECTIVES: This study compared the prognostic role of high on-treatment platelet reactivity (HTPR) in predicting thrombotic events in a Korean population undergoing percutaneous coronary intervention (PCI) in the acute myocardial infarction (AMI) and non-AMI setting. BACKGROUND: The prognostic significance and optimal cutoff of HTPR might differ according to a given clinical condition, such as AMI and ethnicity. METHODS: On-treatment platelet reactivity was measured with a VerifyNow P2Y12 assay (Accumetrics, San Diego, California) in 1,226 patients (824 men; age 65 ± 10 years), including 413 AMI cases, 12 to 24 h after PCI between March 2008 and March 2010. The prevalence of cardiovascular (CV) events defined as a composite of death from CV causes, nonfatal myocardial infarction, or stent thrombosis at 1-year follow-up were compared according to HTPR between patients with and without AMI. RESULTS: The optimal cutoff for HTPR was 272 IU of the P2Y(12) reaction unit (PRU) (area under the curve: 0.708; 95% confidence interval [CI]: 0.607 to 0.809, p = 0.03), which was the upper-tertile threshold. Among AMI patients, 1-year CV events occurred more frequently in patients with versus without HTPR (n = 14 [8.8%] vs. n = 1 [0.4%], p < 0.001), whereas there was no difference in the composite endpoint on the basis of HTPR in patients without AMI (n = 7 [2.8%] vs. n = 8 [1.4%], p = 0.193). CONCLUSIONS: Increased residual platelet reactivity is related to post-discharge CV events in subjects with AMI, whereas the prognostic significance of HTPR seems to be attenuated in patients with stable coronary disease after PCI.

Intravascular ultrasound-guided primary percutaneous coronary intervention with drug-eluting stent implantation in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Studies investigating the clinical outcome of intravascular ultrasound (IVUS)-guided primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI) show conflicting results. The aim of our study was to evaluate whether IVUS-guidedPPCI with drug-eluting stents (DESs) in STEMI patients improves clinical outcome. HYPOTHESIS: IVUS-guided PPCI is superior to angio-guided PPCI. METHODS: Three hundred forty-one patients who underwent PPCI for STEMI and survived the hospitalization were enrolled in this study. Two hundred sixteen (63.3%) patients were treated with angio-guided PPCI and 125 (36.7%) patients were treated with IVUS-guided PPCI. The primary endpoint was defined as the composite of death, myocardial infarction, target vessel revascularization, and target lesion revascularization at the 3-year follow-up visit. RESULTS: Male gender, dyslipidemia, and smoking were frequent in the IVUS-guided PPCI group. These patients had a higher rate of radial approach, adjunctive ballooning, thrombectomy, and the use of a glycoprotein IIb/IIIa inhibitor. The number and length of implanted stents were higher in the IVUS-guided PPCI group. The primary end point (18.1% vs 12.8%, P = 0.22) and stent thrombosis (2.8% vs 2.4%, P = 1.00) was not different between the groups. CONCLUSIONS: In our observational study, IVUS-guided PPCI with DESs in patients with STEMI did not improve clinical outcome or stent thrombosis.

Feasibility of transradial coronary intervention using a sheathless guiding catheter in patients with small radial artery.

BACKGROUND AND OBJECTIVES: Transradial coronary angiography and intervention are increasing in frequency due to lower major vascular access site complications and the potential for early mobilization. However, the small size of the radial artery (RA) is a major limitation of this technique. A sheathless guiding catheter (GC) has recently been introduced that has a 1-2 French smaller diameter compared with the corresponding introducer sheath. This catheter also has a hydrophilic coating along its entire length. We evaluated the feasibility of using a sheathless GC in patients who have small radial arteries. SUBJECTS AND METHODS: The procedural results were evaluated in patients with small radial arteries (diameter <2.3 mm) who underwent transradial coronary intervention using a sheathless GC. RESULTS: A total of 25 (male: 9) patients with 29 lesions were enrolled. The mean RA diameter was 1.81±0.26 mm. 44% of the patients had stable angina and 50.0% had acute coronary syndrome. The procedural success rate was 93.1%. Two patients (6.9%) had chronic total occlusive lesions that could not be crossed with a guide-wire despite good guiding support. An intravascular ultrasound could be used for all of the treated lesions. Multi-vessel intervention was performed in 29.2% of the patients. Two bifurcated lesions were treated with a kissing balloon technique, and one with a modified T-stenting technique. No catheter related complications were reported. CONCLUSION: The use of a sheathless GC is feasible in patients with small radial arteries without catheter related complications.

Normative values and correlates of mean common carotid intima-media thickness in the Korean rural middle-aged population: the Atherosclerosis RIsk of Rural Areas iN Korea General Population (ARIRANG) study.

Carotid intima-media thickness (CIMT) is considered as a surrogate marker for cardiovascular disease (CVD). We determined the normative value of CIMT and correlates of CVD risk factors and Framingham risk score (FRS) in Korean rural middle-aged population. We measured CIMT with a B-mode ultrasonography in 1,759 subjects, aged 40 to 70 yr, in a population-based cohort in Korea. A healthy reference sample (n = 433) without CVD, normal weight and normal metabolic parameters was selected to establish normative CIMT values. Correlates between CIMT and conventional CVD risk factors were assessed in the entire population. Mean values of CIMT (in mm) for healthy reference sample aged 40-49, 50-59, and 60-70 yr were 0.55, 0.59, and 0.66 for men and 0.48, 0.55, and 0.63 for women, respectively. In multivariate regression analysis, CIMT was correlated with older age, higher BMI, male gender, higher LDL-cholesterol level and history of diabetes mellitus. The mean CIMT was also correlated with FRS in both gender (r(2) = 0.043, P < 0.01 for men; r(2) = 0.142, P < 0.01 for women). We identified normative value of CIMT for the healthy Korean rural middle-aged population. The CIMT is associated with age, obesity, gender, LDL-cholesterol, diabetes mellitus and FRS.

Relationships between serum adiponectin with metabolic syndrome and components of metabolic syndrome in non-diabetic Koreans: ARIRANG study.

PURPOSE: Growing evidence suggests that hypoadiponectinemia may play a significant role in the development of metabolic syndrome (MetS). Therefore, the relationships between serum adiponectin with MetS and components of MetS were investigated in non-diabetic samples of drawn from the Koreans general population. MATERIALS AND METHODS: We performed a cross-sectional study in samples of older Koreans (age > 40 years) including 2,471 men and 3,463 women. MetS was defined according to the Asian modified criteria of the National Cholesterol Education Program Adult Treatment Panel III report. Serum adiponectin concentrations were measured by radioimmunoassay. RESULTS: The median adiponectin level in MetS was significantly lower than that in non-MetS subjects in men (6.00 vs. 8.00 µg/mL, p < 0.001) and women (10.12 vs. 11.74 µg/mL, p < 0.001). Adiponectin concentration was negatively correlated with waist circumference and levels of triglyceride, C-reactive protein (CRP), fasting glucose, and insulin, and positively correlated with high-density lipoprotein and age in both genders (p < 0.001). In a multivariate regression model after adjustment for age, body mass index, smoking, CRP, and lipid profiles, the odds ratio of MetS comparing extreme quartiles of adiponectin distribution was 0.32 [95% confidence interval (CI), 0.20 to 0.50] in men and 0.57 (95% CI, 0.43 to 0.76) in women. CONCLUSION: Adiponectin levels are independently associated with the phenotype of MetS, as well as components of MetS in the non-diabetic Korean general population.

Eutectic mixture of local anesthesia cream can reduce both the radial pain and sympathetic response during transradial coronary angiography.

BACKGROUND AND OBJECTIVES: ADIAL ARTERY SPASM IS ONE OF THE MOST COMMON COMPLICATIONS OF TRANSRADIAL CORONARY ANGIOGRAPHY (TRA): the radial artery is prone to cathecholamine-induced contraction and radial pain during TRA could increase the sympathetic tone. The object of this study was to evaluate whether the eutectic mixture of local anesthesia (EMLA) cream, in addition to lidocaine infiltration, could reduce the sympathetic response by reducing radial pain during TRA. SUBJECTS AND METHODS: Seventy-six patients were randomized 1 : 1 to either EMLA or control groups. Radial pain was measured by the visual analogue scale (VAS) and the verbal rating scale (VRS-4). Sympathetic response, including systolic (SBP) and diastolic blood pressure (DBP), pulse rate (PR), stroke volume (SV) and total peripheral resistance (TPR), was measured by photoplethysmography. RESULTS: RADIAL PAIN MEASURED DURING LIDOCAINE INFILTRATION WAS SIGNIFICANTLY LOWER IN THE EMLA GROUP (VAS: 3.1 vs. 4.0, p=0.04; VRS-4: 2.0 vs. 2.2, p=0.03) and the sympathetic response was significantly blunted in the EMLA group from baseline to lidocaine infiltration (ΔSBP, mm Hg: 5 vs. 13, p<0.01; ΔDBP, mm Hg: 2 vs. 7, p=0.03; ΔPR, beat/min: 2 vs. 8, p<0.01, ΔSV, mL: 3 vs. 21, p<0.01; ΔTPR, mm Hg · L/min: 1.0 vs. 5.9, p<0.01). CONCLUSION: In patients undergoing TRA, the EMLA cream, in addition to lidocaine infiltration, effectively reduces the radial pain and thereby the sympathetic response, during lidocaine infiltration.

A case of hypocalcemia-induced dilated cardiomyopathy.

Hypocalcemia is a rare cause of dilated cardiomyopathy. Hypocalcemia induced cardiomyopathy is usually reversible when calcium level returns to normal range. We experienced a case of 57-year-old woman who had suffered from hypocalcemia after total thyroidectomy and its consequence of dilated cardiomyopathy. After supplementation of calcium and vitamin D, symptoms of heart failure and LV function were recovered.

Clinical characteristics and prognostic factors of stress-induced cardiomyopathy.

BACKGROUND AND OBJECTIVES: Stress-induced cardiomyopathy (SCM) is characterized by a transient left ventricular (LV) dysfunction due to emotional and physical stress. There are limited data about the clinical characteristics in Korean patients. We sought to clarify the clinical features and prognosis in patients with SCM. SUBJECTS AND METHODS: We reviewed 39 cases diagnosed with SCM in a tertiary hospital. The SCM was diagnosed as: 1) no previous history of cardiac disease, 2) acute onset, 3) regional wall motion abnormality, typically in the takotsubo or inverted takotsubo shape by echocardiography, and 4) no significant stenosis in the coronary angiogram. We evaluated clinical characteristics, biomarkers, and prognosis. RESULTS: Mean age was 61.3+/-16.1 years (female 69%). The triggering factors were physical stress in 32 patients (82%) and emotional stress in 5 patients (13%). The initial symptom was dyspnea (n=18, 46%) rather than chest pain (n=10, 26%). An initial electrocardiogram (EKG) presented T-wave inversion (n=18, 46%), ST-elevation (n=11, 28%), and ST-depression (n=2, 5%). Multivariate logistic regression analysis showed that initial high sensitive C-reactive protein (hs-CRP) {odds ratio (OR) 1.41, 95% confidence interval (CI); 1.02-1.97} and initial left ventricular ejection fraction (LVEF) (OR 0.89, 95% CI; 0.80-0.98) were significantly associated with death or cardiogenic shock, respectively. CONCLUSION: The major triggering factor of SCM is physical stress due to illness or surgical procedures, and the first manifestation is dyspnea rather than chest pain. Elevated hs-CRP and decreased LVEF at admission were independent risk factors for death or cardiogenic shock.

Cardiovascular parameters correlated with metabolic syndrome in a rural community cohort of Korea: the ARIRANG study.

Although metabolic syndrome (MetS) is associated with increased cardiovascular mortality and the development of atherosclerosis, consensus is still lacking on the status of cardiovascular function and geometry in MetS patients. We investigated the relation between MetS and left ventricle (LV) geometry and function, carotid intima-media thickness (IMT) and arterial stiffness in a community-based cohort of 702 adult subjects. Subjects were categorized into three groups according to the number of MetS components present, as defined by the Adult Treatment Panel III guidelines: 1) Absent (0 criteria), 2) Pre-MetS (1-2 criteria) or 3) MetS (> or =3 criteria). In female subjects, LV mass, LV mass/height(2.7), deceleration time, and aortic pulse wave velocity increased, and E/A ration decreased in a stepwise manner across the three groups. These changes were not observed in male subjects. The mean carotid IMT was higher in the MetS group than in the other two groups. The degree of MetS clustering is found to be strongly correlated with geometric eccentricity of LV hypertrophy, diastolic dysfunction and arterial changes irrespective of age and blood pressure status, particularly in females. Waist circumference is found to have the most powerful effect on cardiovascular parameters.

Mutations of the GLA gene in Korean patients with Fabry disease and frequency of the E66Q allele as a functional variant in Korean newborns.

Fabry disease is caused by an alpha-galactosidase A (GLA) deficiency. In this study, we identified 28 unrelated Korean families with Fabry disease with 25 distinct mutations in the GLA gene including six novel mutations (p.W47X, p.C90X, p.D61EfsX32, IVS4(-11)T>A, p.D322E and p.W349). Notably, five subjects from four unrelated families carried the p.E66Q variant, previously known as a pathogenic mutation in atypical Fabry disease. Among these patients, only one had proteinuria and two had hypertrophic cardiomyopathy without any other systemic manifestation of Fabry disease. Substantial residual GLA activity was shown both in the leukocytes of p.E66Q patients (19.0-30.3% of normal activity) and in transiently overexpressed COS-7 cells (43.8 + or - 3.03% of normal activity). Although GLA harboring p.E66Q is unstable at neutral pH, the enzyme is efficiently expressed in the lysosomes of COS-7 cells. The location of p.E66 is distant from both the active site and the dimer interface, and has a more accessible surface area than have other mutations of atypical Fabry disease. In addition, the allele frequency of p.E66Q determined in 833 unrelated Korean individuals was remarkably high at 1.046% (95% confidence interval, 0.458-1.634%). These results indicate that p.E66Q is a functional polymorphism rather than a pathogenic mutation.