Changes in Serum Fibroblast Growth Factor 23 in Patients With Acute Myocardial Infarction.

BACKGROUND: Fibroblast growth factor 23 (FGF23) induces cardiac remodeling. We investigated the changes in serum FGF23 levels in patients diagnosed with acute myocardial infarction (AMI).Methods and Results:A total of 44 patients diagnosed with AMI were included in the current study. All patients underwent emergency percutaneous coronary intervention (PCI). The median of peak creatine kinase (CK) and CKMB values was 1,816 U/L and 159 U/L, respectively. Serum levels of FGF23, calcium, and inorganic phosphate (iP) were measured before PCI, and on days 1, 3, 5, 7 after PCI. Serum FGF23 levels showed a slight, but significant decrease on days 1 and 3 after PCI, and a 1.5- and 2.0-fold increase on days 5 and 7, respectively, after PCI. As compared with propensity score-matched patients without AMI, serum FGF23 was significantly lower among the current cohort of AMI patients. In 22 subjects who underwent a follow-up echocardiographic examination at 6 months after the onset of AMI, the log-transformed relative increase in FGF23 on day 7 significantly and negatively correlated with changes between LVEF on admission and that at 6 months afterward. CONCLUSIONS: After a slight decrease on days 1 and 3 after admission, serum FGF23 increased significantly on days 5 and 7. The underlying mechanism and potential clinical importance of these observations require further investigation.

Spontaneous Reduction in Abnormal Myocardial Uptake of Fluorine-18 Fluorodeoxygluose in a Patient with Cardiac Sarcoidosis.

Fluorine-18 fluorodeoxygluose (18F-FDG) positron emission tomography (PET) is a useful tool for evaluating disease activity in sarcoidosis including cardiac involvement. A 67-year-old patient who developed atrioventricular block requiring permanent pacemaker implantation was diagnosed with cardiac sarcoidosis. The patient did not undergo steroid or immunosuppressive therapy but underwent serial 18F-FDG PET examination, which showed spontaneous reduction in the myocardial FDG uptake, indicating the remission of immune-inflammatory activity. Although the global systolic function remained preserved, thinning of the septal wall emerged during the clinical course of follow-up, which is characteristic for cardiac sarcoidosis.

A Case of Aortic Stenosis with Serum IgG4 Elevation, and IgG4-Positive Plasmacytic Infiltration in the Aortic Valve, Epicardium, and Aortic Adventitia.

A 74-year-old man was admitted for preoperative screening of aortic stenosis. Five months before this admission, he was found to have elevated serum immunoglobulin G4 (IgG4; 2,010 mg/dL). Computed tomography (CT) showed a soft tissue mass surrounding the abdominal aorta, suggestive of IgG4-related periaortitis. CT coronary angiography showed perivascular thickening of the right coronary artery, and subsequent coronary angiography showed a multi-vessel disease. The patient underwent aortic valve replacement and coronary bypass surgery. Immunohistochemical analysis showed IgG4-positive plasmacytic infiltration in specimens from the aortic valve, epicardium, and aortic adventitia, suggestive of the possible role of IgG4-related immune inflammation for the pathogenesis.

IgG4-positive cell infiltration in various cardiovascular disorders - results from histopathological analysis of surgical samples.

BACKGROUND: The diagnosis of Immunoglobulin G4 (IgG4)-related disease (IgG4-RD), in general, depends on serum IgG4 concentrations and histopathological findings; therefore, diagnosis of IgG4-RD in cardiovascular organs/tissues is often difficult owing to the risk of tissue sampling. METHODS: Prevalence of IgG4-positive lymphoplasmacytic infiltration in 103 consecutive cardiovascular surgical samples from 98 patients with various cardiovascular diseases was analyzed immunohistochemically. RESULTS: The diagnoses of the enrolled patients included aortic aneurysm (abdominal, n = 8; thoracic, n = 9); aortic dissection (n = 20); aortic stenosis (n = 24), aortic regurgitation (n = 10), and mitral stenosis/regurgitation (n = 17). In total, 10 (9.7%) of the 103 specimens showed IgG4-positive cell infiltration with various intensities; five of these were aortic valve specimens from aortic stenosis, and IgG4-positive cell infiltration was present at >10 /HPF in three of them. In one aortic wall sample from an abdominal aortic aneurysm, various histopathological features of IgG4-RD, such as IgG4-positive cell infiltration, obliterating phlebitis, and storiform fibrosis, were observed. CONCLUSIONS: IgG4-positive cell infiltration was observed in 9.7% of the surgical cardiovascular specimens, mainly in the aortic valve from aortic stenosis and in the aortic wall from aortic aneurysm. Whether IgG4-positive cell infiltration has pathophysiological importance in the development or progression of cardiovascular diseases should be investigated in future studies.

Association between suPAR and cardiac diastolic dysfunction among patients with preserved ejection fraction.

Serum levels of the soluble urokinase-type plasminogen activator receptor (suPAR) reflect immune and inflammatory activation, and are shown to be associated with cardiovascular outcomes. We herein investigated the potential association between suPAR and left ventricular diastolic dysfunction among patients with preserved left ventricular ejection fraction (LVEF) and sinus rhythm. Among 291 patients who had sinus rhythm and an LVEF of ≥50% enrolled in the study, 26 (8.9%) were considered to have diastolic dysfunction. Patients with diastolic dysfunction had lower estimated glomerular filtration rate (eGFR), and higher systolic blood pressure (BPs), BNP, C-reactive protein, and suPAR than those without diastolic dysfunction. As compared with the first suPAR quartile, the fourth suPAR quartile was significantly associated with both diastolic dysfunction with an odds ratio of 8.95 [95% confidence interval (CI), 1.04-77.0, P < 0.05] after adjusting for sex, age, BPs log(eGFR), CRP, and diuretic use. On the other hand, receiver-operating characteristic curve (ROC) analysis showed that addition of log(suPAR) to the combination of age, sex, and log(eGFR), CRP, and diuretic use did not significantly improve the prediction of diastolic dysfunction. Among cardiac patients with preserved LVEF, serum suPAR was associated with diastolic dysfunction independent of confounding factors by logistic regression analysis. However, according to the ROC analysis, the utility of suPAR as a biomarker for diastolic dysfunction may be limited from a clinical point of view.

Is Serum Uric Acid Independently Associated With Left Ventricular Mass Index, Ejection Fraction, and B-Type Natriuretic Peptide Among Female and Male Cardiac Patients?

Mean serum uric acid (SUA) levels are higher in men than women. In addition, recent studies have suggested that the SUA threshold at which the cardiovascular risk might increase may vary between women and men. In the current retrospective study, by analyzing the data from 219 female and 519 male patients who were free from uric acid-lowering medication, we investigated whether SUA is associated with left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), and plasma levels of B-type natriuretic peptide (BNP) independent of confounding factors, such as serum calcium, inorganic phosphate, and fibroblast growth factor 23 (FGF23), in a gender-specific manner.In multivariate stepwise linear regression analysis in which age, blood pressure, eGFR, corrected calcium, inorganic phosphate, and FGF23 were entered as potential covariates, SUA was selected as a factor significantly associated with LVEF, LVMI, and plasma levels of BNP in both genders. On the other hand, however, after adding diuretic use as a potential covariate, the association between SUA and LVEF lost statistical significance in both genders, and that between SUA and BNP lost significance among female patients. These findings suggest that diuretic use is a non-negligible confounder in understanding the observed association between SUA and cardiac dysfunction and heart failure.In summary, SUA is associated with left ventricular hypertrophy independent of confounding factors including FGF23 and diuretic use in female and male patients. Whether lowering SUA can influence the progression of cardiac remodeling awaits further investigation.

Association between absolute blood eosinophil count and CKD stages among cardiac patients.

Elevated eosinophil count was shown to be associated with the development of cholesterol embolization syndrome, a potentially life-threatening condition, after catheter-based procedures. We investigated the association between stages of chronic kidney disease (CKD) and the absolute eosinophil count (AEC) among cardiac patients. CKD stages were determined solely on the estimated glomerular filtration rate or requirement for hemodialysis. Eosinophilia is defined as an eosinophil count exceeding 500/µL. A total of 1022 patients were enrolled in the current study, and eosinophil counts (/µL) in the first through fourth eosinophil count quartiles were <88, 88 to 154, 155 to <238, and 238 ≤, respectively, and 29 patients (2.8 %) had eosinophilia. Correlation coefficient between the AEC and age was -0.188 (P = 0.001) in women and -0.042 (n.s.) in men (by Spearman's correlation test). Patients with higher CKD stages had a higher prevalence of the highest AEC quartile or eosinophilia. Logistic regression analysis using severe renal dysfunction (i.e., CKD stage 4 or 5) as the dependent variable, the highest AEC quartile had a significant positive association with an odds ratio of 1.99 (95 % confidence interval, 1.20-3.31, P < 0.01) after adjustment for sex, age, systolic blood pressure, and total white blood cell count. Similarly, after adjustment for the same variables, eosinophilia was associated with severe renal dysfunction with an odds ratio of 2.60 (95 % confidence interval, 1.08-6.26, P < 0.05). Eosinophil count was positively associated with higher CKD stages among cardiology patients, some fraction of which might be related to subclinical cholesterol embolization.

Association between circulating FGF23, α-Klotho, and left ventricular diastolic dysfunction among patients with preserved ejection fraction.

Besides regulating calcium-phosphate metabolism, fibroblast growth factor-23 (FGF23) and Klotho have been proposed to have other roles in heart and vasculature. For example, FGF23 has been associated with cardiac hypertrophy and reduced left ventricular ejection fraction among patients with chronic kidney disease and cardiovascular disorders. The purpose of the study was to investigate whether serum FGF23 and α-Klotho concentrations are associated with cardiac diastolic dysfunction and related parameters among cardiac patients with preserved left ventricular ejection fraction. The current study enrolled 269 patients (69 women, 200 men) who were admitted to our cardiology department between October 2012 and January 2014 and had a left ventricular ejection fraction of >50%. Cardiac diastolic function was assessed by blood flow and tissue Doppler velocities, plasma B-type natriuretic peptide (BNP) concentration, and cardiac hypertrophy. After adjusting for sex, and age, logistic regression analysis showed that log(α-Klotho), but not log(FGF23), was significantly associated with diastolic dysfunction. After further adjustment for renal function, blood hemoglobin, and serum albumin levels, the negative association between log(α-Klotho) and diastolic dysfunction retained statistical significance with an odds ratio of 0.50 (95% confidence interval 0.31-0.81, P = 0.005, per 1 standard deviation). Among patients with preserved LVEF, serum α-Klotho concentrations were negatively associated with diastolic dysfunction. Whether modulation of serum levels α-Klotho will ameliorate cardiac diastolic function among patients with this disorder awaits further investigation.

Serum uric acid is associated with cardiac diastolic dysfunction among women with preserved ejection fraction.

Serum uric acid (SUA) is associated with the severity and prognosis of systolic heart failure. We investigated the potential association between SUA and cardiac diastolic dysfunction among total of 744 cardiac patients (202 women and 542 men) who had preserved left ventricular ejection fraction. Presence of diastolic dysfunction was assessed by echocardiographic data, plasma B-type natriuretic peptide concentration, and left ventricular hypertrophy. Univariate analysis showed that the prevalence of diastolic dysfunction increased with increasing SUA value in women, but not in men. When sex-nonspecific SUA quartiles were used, multivariate logistic regression analysis, among female patients who were not taking uric acid lowering medication, showed that the third (SUA, 5.7-6.4 mg) and the fourth (SUA, ≥6.5 mg/dl) SUA quartiles were associated with diastolic dysfunction with an odds ratio of 3.25 (P < 0.05) and 8.06 (P < 0.001), respectively, when compared with the first SUA quartile (≤4.7 mg/dl). When sex-specific SUA quartiles were used among these population, multivariate logistic regression analysis showed that the fourth SUA quartile (≥5.7 mg/dl) was associated with diastolic dysfunction with an odds ratio of 5.34 (P < 0.05) when compared with the first SUA quartile (≤4.1 mg/dl). By contrast, the relationship between SUA and diastolic dysfunction was not significant in men, irrespective of which of the sex-nonspecific or sex-specific SUA quartiles were used. These data indicated that among cardiac patients with preserved ejection fraction, SUA was significantly associated with diastolic dysfunction in women but not in men.

Circulating Fibroblast Growth Factor 23 Has a U-Shaped Association With Atrial Fibrillation Prevalence.

BACKGROUND: Atrial fibrillation (AF) occurs more frequently among patients with renal dysfunction. We investigated the possible association between prevalence of AF and serum fibroblast growth factor 23 (FGF23), which has been shown to be increased in subjects with renal dysfunction. METHODS AND RESULTS: Among the total enrollment of 851 cardiac patients, 188 patients had AF (paroxysmal AF, 95; non-paroxysmal AF, 93). Prevalence of AF for FGF23 octile had a U-shaped relationship with the lowest prevalence at the fifth octile. On logistic regression analysis, when the third FGF23 quartile was used as the reference, the first and fourth FGF23 quartiles were associated with prevalence of AF with an odds ratio (OR) of 3.34 (95% confidence interval [CI]: 1.89-5.88) and 2.58 (95% CI: 1.45-4.58), respectively, after adjusting for confounding factors including estimated glomerular filtration rate (eGFR). Among the subgroup of 416 patients for whom serum parathyroid hormone and 25-hydroxy vitamin D data were available, OR of the first and the fourth FGF23 quartile were calculated to be 3.52 and 2.97, respectively, when further adjusted for these two variables in the statistical model. CONCLUSIONS: Serum FGF23 had a U-shaped relationship with prevalence of AF among Japanese cardiac patients, which was independent of other calcium/phosphate metabolism-related parameters and eGFR. Pathophysiology underlying the observed link, if at all, awaits further investigation.

The relationship of fibroblast growth factors 21 and 23 and α-Klotho with platelet activity measured by platelet volume indices.

BACKGROUND: Subjects with high fibroblast growth factor 21(FGF21) and 23 (FGF23), endocrine hormones that regulate insulin sensitivity and phosphate metabolism, respectively, are reported to have a higher risk for adverse cardiovascular outcome. Therefore, the relationship of FGF21, FGF23, and α-Klotho (co-receptor for FGF23 signaling) with mean platelet volume (MPV) and platelet distribution width (PDW), two platelet volume indices that reflect platelet activity, was investigated. METHODS: Data from 156 patients admitted to the cardiology department were analyzed. MPV and PDW were measured by an automatic blood counter, and serum FGF21, FGF23, and α-Klotho concentrations were measured by an enzyme-linked immunoassay. RESULTS: Log(FGF21) was significantly correlated with serum triglycerides but did not differ according to the use of non-use of antidiabetic or lipid-lowering drugs. MPV and PDW were significantly correlated (R=0.475, p<0.001). MPV was significantly correlated with log(FGF21) (R=-0.167, p<0.05) and log(FGF23) (R=0.351, p<0.001) but not with log(α-Klotho). Linear regression analysis showed a negative and positive association of log(FGF21) and log(FGF23), respectively, with MPV that was independent of possible confounders including sex, age, renal function, and antithrombotic drug use. In addition, log(FGF23) was found to have a significant independent positive association with PDW. CONCLUSIONS: Among cardiac patients, FGF21 had a negative association with MPV, whereas FGF23 had a positive association. Future studies of serum FGF23/FGF21 concentrations and the incidence of thromboembolic disorders are warranted.

Platelet volume indices are associated with systolic and diastolic cardiac dysfunction, and left ventricular hypertrophy.

BACKGROUND: Mean platelet volume (MPV) and platelet distribution width (PDW) are indices that reflect platelet activity. We investigated the association between these platelet indices and left ventricular hypertrophy and cardiac function. METHODS: We analyzed the data of 1241 patients who were admitted to the Cardiology Department. RESULTS: Both MPV and PDW were selected as independent factors associated with left ventricular systolic and diastolic dysfunction, and left ventricular hypertrophy. The highest tertile of MPV and PDW was associated with left ventricular systolic dysfunction (left ventricular ejection fraction of <50 %) with an odds ratio of 1.53 and 2.03, respectively, when the respective lowest tertile was used as reference. The highest PDW tertile was associated with left ventricular hypertrophy with an odds ratio of 1.56 (95 % CI, 1.13-2.15) and with dysfunction with an odds ratio of 3.34 (95 % CI, 1.54-7.25). CONCLUSIONS: Indices of platelet activation (MPV and/or PDW) were independently associated positively with left ventricular hypertrophy and left ventricular systolic and diastolic dysfunction. Whether these platelet indices represent useful markers for identifying individuals at higher risk for thromboembolic disease and organ damage among cardiac patients awaits further investigation.

Association of serum levels of FGF23 and α-Klotho with glomerular filtration rate and proteinuria among cardiac patients.

BACKGROUND: Expression and/or excretion of fibroblast growth factor-23 (FGF23) and its co-receptor Klotho are altered in patients with end-stage renal disease. The possibility that the FGF23/α-Klotho system mediates the aggravated cardiovascular outcome among patients with chronic kidney disease (CKD) has been suggested. We determined whether FGF23 and α-Klotho concentrations are altered among patients with reduced renal function and proteinuria. METHODS: Serum FGF23 and α-Klotho were measured in cardiology patients who were not undergoing chronic hemodialysis. Estimated glomerular filtration rate (eGFR) was correlated negatively with FGF23 and positively with α-Klotho. RESULTS: The correlation between FGF23 and the renal tubular maximum reabsorption rate of phosphate to the GFR (TmP/GFR) was not significant, but that between FGF23 and serum calcium or inorganic phosphate was significant among patients with an estimated GFR of less than 60 mL/min/m(2). By stepwise multivariate regression analysis, eGFR was selected as significant predictor for FGF23 or α-Klotho among patients with an estimated GFR of less than 60 mL/min/m(2); however, urine albumin/creatinine ratio was not selected as a predictor for FGF23 or α-Klotho irrespective of the eGFR levels. In patients with eGFR of <60 mL/min/1.73 m(2), UACR was significantly associated with log(FGF23); but, this association did not remain statistically significant in a multivariate model. CONCLUSIONS: Among cardiology patients with various stages of CKD, serum concentrations of FGF23 and α-Klotho were associated with renal function, but not with the extent of proteinuria.

Hypoplastic Left Atrial Appendage: A Case Report and Literature Review.

BACKGROUND The left atrial appendage (LAA) has considerable variations in its size, shape, and spatial relationship with other cardiac structures. Absence of the LAA is a congenital cardiac condition usually identified by an imaging modality intended for other purposes. Absence of the LAA has been described in a total of 19 case reports so far; however, no cases of "hypoplastic" LAA in a real sense have ever been reported. CASE REPORT We herein report a case of hypoplastic, but not truly absent, LAA in a 76-year-old man scheduled for catheter ablation against atrial flutter. Preprocedural transesophageal echocardiography (TEE) performed in this patient to exclude intracardiac thrombosis failed to detect the LAA, although Doppler color-flow mapping revealed a jet signal spewed out into the main LA around where the LAA would be located. The LAA was also not detectable by routinely developed tomographic images from computed tomography (CT) angiography. Eventually, however, the multiplanar reconstruction into 3-dimensional volume rendering via the CT angiography identified a very small LAA. Those findings by TEE and CT led to a diagnosis of hypoplastic LAA. CONCLUSIONS Hypoplastic LAA should be kept in mind when considering LAA interventions as well as anticoagulation treatment. Multiple imaging modalities are necessary to recognize morphological aberration of the LAA.

Transient depression of myocardial function after influenza virus infection: A study of echocardiographic tissue imaging.

BACKGROUND: Influenza virus infection (IVI) was reported to be associated with minor cardiac changes, mostly those detected on electrocardiogram with and without elevated blood markers of myocardial injury; however, the characteristics of myocardial involvement in association with IVI are poorly understood. This study used echocardiographic tissue imaging (tissue Doppler, strain, and strain rate) to evaluate changes in left atrial (LA) and left ventricular (LV) myocardial function after IVI. METHODS AND RESULTS: We examined 20 adult individuals (mean age, 43 years) at 2 and 4 weeks after diagnosis of IVI. For myocardial functional variables, we obtained LV global longitudinal strain (GLS), LV early diastolic strain rate (e'sr), LA strain, and LA stiffness (E/e'/LA strain), in addition to data on tissue Doppler (s', e', and a') and myocardial performance index. Blood markers of myocardial injury were also examined. During follow-up, there were no significant changes in global chamber function such as LV ejection fraction, E/e', and LA volume. However, significant changes in myocardial function were observed, namely, in s' (8.0 ± 1.6 cm/s to 9.3 ± 1.5 cm/s; p = 0.01), e' (10.2 ± 2.8 cm/s to 11.4 ± 3.0 cm/s; p < 0.001), e'sr (1.43 ± 0.44 1/s to 1.59 ± 0.43 1/s; p = 0.005), and LA strain (35 ± 8% to 40 ± 12%; p = 0.025), and the myocardial performance index (0.52 ± 0.20 to 0.38 ± 0.09; p = 0.009), but not in a', LA stiffness, or GLS. Cardiac troponin T and creatinine kinase isoenzyme MB were not elevated significantly at any examination. CONCLUSIONS: Myocardial dysfunction during IVI recovery appeared to be transient particularly in the absence of myocardial injury. Echocardiographic tissue imaging may be useful to detect subclinical cardiac changes in association with IVI.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) with an Unusual Manifestation of Mid-Ventricular Obstruction Caused by Endocardial Thrombus.

BACKGROUND Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis of unknown cause accompanied by prominent eosinophilia. Intracardiac thrombosis is one of the major cardiac complications in EGPA that may cause thromboembolism. CASE REPORT A 46-year-old male presenting with intermittent chest pain and numbness of the lower extremities was admitted to our center. His case was complicated by multiple brain infarcts and endocardial thrombosis in the left ventricle. A condition of restrictive cardiomyopathy was also found. After a thorough workup, he was diagnosed with antineutrophil cytoplasmic antibody (ANCA) positive EGPA. Interestingly, the thrombus was accompanied by a pressure gradient producing mid-ventricular obstruction. The patient improved reasonably with immunosuppression and anticoagulation treatment, in addition to heart failure treatment, and had a concomitant regression of the thrombus and reduction of the pressure gradient. CONCLUSIONS For an EGPA patient complicated by intraventricular obstruction caused by endocardial thrombosis, which could accelerate the release of the thrombus into the systemic circulation resulting in a life-threating condition, timely and aggressive measures against cardioembolic complications should be considered.

High serum bilirubin is associated with lower prevalence of peripheral arterial disease among cardiac patients.

Several studies have shown that subjects with higher serum bilirubin may have a lower risk of cardiovascular disorders. We herein investigated whether serum bilirubin concentration is associated with lower extremity ischemia among cardiology patients. In total, 935 patients without a history of angioplasty or bypass surgery of the lower limb arteries and who had bilateral ankle-brachial index measurements were included in the study. Peripheral arterial disease (PAD) was defined to be present when ABI of either or both sides was <0.9. Overall, the serum total bilirubin concentration ranged between 0.1 and 2.7mg/dL (normal range, 0.1-1.0mg/dL). Across the bilirubin tertiles, age did not differ significantly. On the other hand, male patients (median 0.6mg/dL, interquartile range (IQR) 0.4-0.7mg/dL) had significantly higher bilirubin levels than female patients (median 0.5mg/dL, IQR 0.4-0.7mg/dL, P=0.014). Logistic regression analysis showed that, as compared with the lowest bilirubin tertile (0.1-0.4mg/dL), the highest tertile (0.7-2.7mg/dL) was significantly negatively associated with prevalent PAD after adjusting for sex, age, eGFR, white blood cell count, inorganic phosphate, HbA1C, total and HDL cholesterol, triglycerides, current smoking, diabetic medication, and statin use. This association remained significant when only those with serum bilirubin in the normal range were included in the analysis. Among cardiology patients, serum bilirubin concentration was significantly negatively associated with prevalence of PAD. The underlying mechanism and therapeutic indications should be investigated in further investigations.

Serum Soluble Urokinase-Type Plasminogen Activator Receptor Is Associated with Low Left Ventricular Ejection Fraction and Elevated Plasma Brain-Type Natriuretic Peptide Level.

BACKGROUND: Recent studies have suggested that soluble urokinase plasminogen activator receptor (suPAR), a biomarker of subclinical levels of inflammation, is significantly correlated with cardiovascular events. PURPOSE: We investigated the association between suPAR and left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), and plasma B-type natriuretic peptide (BNP) among cardiac inpatients. METHODS AND RESULTS: In total, 242 patients (mean age 71.3 ± 9.8 years; 70 women) admitted to the cardiology department were enrolled in the study. suPAR was significantly correlated with LVEF (R = -0.24, P<0.001), LVMI (R = 0.16, P = 0.014) and BNP (R = 0.46, P<0.001). In logistic regression analysis, the highest suPAR tertile (> 3236 pg/mL) was associated with low LVEF (< 50%) and elevated BNP (> 300 pg/mL) with an odds ratio of 3.84 (95% confidence interval [CI], 1.22-12.1) and 5.36 (95% CI, 1.32-21.8), respectively, after adjusting for age, sex, log-transformed estimated glomerular filtration rate (log(eGFR)), C-reactive protein, and diuretic use. The association between suPAR and LVMI was not statistically significant. In multivariate receiver operating characteristic analysis, addition of log(suPAR) to the combination of age, sex, log(eGFR) and CRP incrementally improved the prediction of low LVEF (area under the curve [AUC], 0.827 to 0.852, P = 0.046) and BNP ≥ 300 pg/mL (AUC, 0.869 to 0.906; P = 0.029). CONCLUSIONS: suPAR was associated with low LVEF and elevated BNP, but not with left ventricular hypertrophy, independent of CRP, renal function, and diuretic use among cardiac inpatients who were not undergoing chronic hemodialysis.

Association between serum soluble urokinase-type plasminogen activator receptor and atrial fibrillation.

BACKGROUND: Circulating soluble urokinase-type plasminogen activator receptor (suPAR), which can reflect immune activation and low-grade inflammation, may be a novel biomarker of cardiovascular disease. METHODS: We investigated the potential association between suPAR and the prevalence of atrial fibrillation (AF) by analyzing patients with either sinus rhythm, paroxysmal atrial fibrillation (PAF), or non-paroxysmal atrial fibrillation (NPAF), which indicates either permanent or persistent AF. RESULTS: Among 426 patients enrolled (mean age 71.4±9.2 years; 110 (25.8%) female), 310, 62, and 54 were diagnosed with sinus rhythm, PAF, and NPAF, respectively. NPAF was >10-fold more prevalent in the highest suPAR quartile (>3534 pg/mL; 32 (30.2%) of 106 patients) than in the lowest suPAR quartile (<1802 pg/mL; 3 (2.8%) of 107 patients). Logistic regression analysis showed that, as compared with the lowest suPAR quartile, the highest suPAR quartile was associated with NPAF with an odds ratio of 6.48 (95% confidence interval, 1.71-24.5) after adjustment for sex, age, log(eGFR), C-reactive protein, and systolic blood pressure. In multivariate receiver operating characteristic analysis to predict NPAF, the area under the curve (AUC) for the combination of age, sex, log(eGFR), and C-reactive protein was 0.777 (standard error [SE], 0.036); the addition of log(suPAR) slightly improved the prediction (AUC, 0.812; SE, 0.034, P=0.084). CONCLUSIONS: Serum suPAR was associated with AF, particularly NPAF, as demonstrated by multivariate logistic regression analysis. Whether suPAR promotes or maintains AF should be investigated in further studies.

Relationship between plasma xanthine oxidoreductase activity and left ventricular ejection fraction and hypertrophy among cardiac patients.

BACKGROUND AND PURPOSE: Xanthine oxidoreductase (XOR), which catalyzes purine catabolism, has two interconvertible forms, xanthine dehydrogenase and xanthine oxidase, the latter of which produces superoxide during uric acid (UA) synthesis. An association between plasma XOR activity and cardiovascular and renal outcomes has been previously suggested. We investigated the potential association between cardiac parameters and plasma XOR activity among cardiology patients. METHODS AND RESULTS: Plasma XOR activity was measured by [13C2,15N2]xanthine coupled with liquid chromatography/triplequadrupole mass spectrometry. Among 270 patients who were not taking UA-lowering drugs, XOR activity was associated with body mass index (BMI), alanine aminotransferase (ALT), HbA1c and renal function. Although XOR activity was not associated with serum UA overall, patients with chronic kidney disease (CKD), those with higher XOR activity had higher serum UA among patients without CKD. Compared with patients with the lowest XOR activity quartile, those with higher three XOR activity quartiles more frequently had left ventricular hypertrophy. In addition, plasma XOR activity showed a U-shaped association with low left ventricular ejection fraction (LVEF) and increased plasma B-type natriuretic peptide (BNP) levels, and these associations were independent of age, gender, BMI, ALT, HbA1C, serum UA, and CKD stages. CONCLUSIONS: Among cardiac patients, left ventricular hypertrophy, low LVEF, and increased BNP were significantly associated with plasma XOR activity independent of various confounding factors. Whether pharmaceutical modification of plasma XOR activity might inhibit cardiac remodeling and improve cardiovascular outcome should be investigated in future studies.