Metabolic syndrome is linked to the incidence of pancreatic cancer.

Background: Although previous studies have showed that metabolic syndrome is one of the contributors of pancreatic cancer, there is no clear consensus that early stages of metabolic syndrome are linked to increased incidence of pancreatic cancer. Therefore, we confirmed the linkage between metabolic syndrome and pancreatic cancer, and shown that even early stage of metabolic syndrome is linked to pancreatic cancer in the retrospective observational study. Methods: We recruited approximately 4.6 million Japanese in 2005 and followed up these subjects for more than 10 years. At the time of the enrollment, after obtaining clinical data with prescribed drugs and examining the presence or absence of metabolic syndrome (MetS), we followed up on these subjects with and without MetS to examine the incidence of pancreatic cancer. The modified criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII) were used to define MetS. Findings: During the 40.7-month average follow-up period for 2,707,296 subjects with complete data for identifying MetS and important risk factors without pancreatic cancer before the enrollment, 87,857 suffered from pancreatic cancer. Pancreatic cancers occurred in 16,154 of 331,229 subjects (4.9%) in the MetS group and 71,703 of 2,376,067 patients (3.0%) in the non-MetS group (hazard ratio (HR), 1.37; 95% confidence interval [CI], 1.34-1.39; p < 0.0001 after the adjustment with age, smoking and sex). As the number of the constituent factors of MetS increased from one to five, the incidence of pancreatic cancer correspondingly increased (HR: 1.11, 1.23, 1.42, 1.66 and 2.03 using Cox proportional hazard models, p < 0.0001 each). When we defined MetS using the Japanese criteria, the results are in accord with the results using NCEP/ATPIII. Especially pre-metabolic syndrome (pre-MetS) in the Japanese criteria was tightly linked to the incidence of pancreatic cancers. Interpretation: MetS is confirmed to be linked to pancreatic cancer. Although we cannot conclude causality. We also demonstrated the link between pre-MetS and pancreatic cancer. Funding: The sponsors of the study were Japanese Heart Foundation and Japan Cardiovascular Research Foundation. This is also partially supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and Grants-in-Aid from the Japan Agency for Medical Research and Development.

Predicting heart failure onset in the general population using a novel data-mining artificial intelligence method.

We aimed to identify combinations of clinical factors that predict heart failure (HF) onset using a novel limitless-arity multiple-testing procedure (LAMP). We also determined if increases in numbers of predictive combinations of factors increases the probability of developing HF. We recruited people without HF who received health check-ups in 2010, who were followed annually for 4 years. Using 32,547 people, LAMP was performed to identify combinations of factors of fewer than four factors that could predict the onset of HF. The ability of the method to predict the probability of HF onset based on the number of matching predictive combinations of factors was determined in 275,658 people. We identified 549 combinations of factors for the onset of HF. Then we classified 275,658 people into six groups who had 0, 1-50, 51-100, 101-150, 151-200 or 201-250 predictive combinations of factors for the onset of HF. We found that the probability of HF progressively increased as the number of predictive combinations of factors increased. We identified combinations of variables that predict HF onset. An increased number of matching predictive combinations for the onset of HF increased the probability of HF onset.

Artificial Intelligence Uncovered Clinical Factors for Cardiovascular Events in Myocardial Infarction Patients with Glucose Intolerance.

PURPOSE: Glucose intolerance (GI), defined as either prediabetes or diabetes, promotes cardiovascular events in patients with myocardial infarction (MI). Using the pooled clinical data from patients with MI and GI in the completed ABC and PPAR trials, we aimed to identify their clinical risk factors for cardiovascular events. METHODS: Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 415,328 combinations of < 4 clinical parameters. RESULTS: We identified 242 combinations that predicted the occurrence of hospitalization for (1) percutaneous coronary intervention for stable angina, (2) non-fatal MI, (3) worsening of heart failure (HF), and (4) all causes, and we analyzed combinations in 1476 patients. Among these parameters, the use of proton pump inhibitors (PPIs) or plasma glucose levels > 200 mg/dl after 2 h of a 75 g oral glucose tolerance test were linked to the coronary events of (1, 2). Plasma BNP levels > 200 pg/dl were linked to coronary and cardiac events of (1, 2, 3). Diuretics use, advanced age, and lack of anti-dyslipidemia drugs were linked to cardiovascular events of (1, 3). All of these factors were linked to (4). Importantly, each finding was verified by independently drawn Kaplan-Meier curves, indicating that the determined factors accurately affected cardiovascular events. CONCLUSIONS: In most previous MI patients with GI, progression of GI, PPI use, or high plasma BNP levels were linked to the occurrence of coronary stenosis or recurrent MI. We emphasize that use of AI may comprehensively uncover the hidden risk factors for cardiovascular events.

Plasma BNP Levels and Diuretics Use as Predictors of Cardiovascular Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance.

PURPOSE: Although impaired glucose tolerance (IGT) promotes cardiovascular events, our Alpha-glucosidase-inhibitor Blocks Cardiac Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance (ABC) study showed that alpha-glucosidase inhibitors do not prevent cardiovascular events in patients with myocardial infarction (MI) and IGT. The aim of the present study was to identify potential clinical factors for cardiovascular events in patients with MI and IGT. METHODS: Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 385,391 combinations of fewer than four clinical parameters. RESULTS: We identified 380 combinations predicting the occurrence of (1) all-cause hospitalization, (2) hospitalization due to worsening of heart failure (HF), (3) hospitalization due to non-fatal MI, and (4) hospitalization due to percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for stable angina among 385,391 combinations in 853 patients. Among these, either plasma BNP levels ≥ 200 pg/dl or diuretic use exclusively predicted (1) all-cause hospitalization, (2) hospitalization due to worsening of HF, and (3) hospitalization due to a non-fatal MI, with plasma BNP levels ≥ 200 pg/dl being the sole predictor of hospitalization due to PCI and CABG. Importantly, each finding was verified by independently drawn Kaplan-Meier curves, revealing the unexpected role of plasma BNP levels in the progression of coronary stenosis determined as the necessity of PCI and CABG for stable angina. CONCLUSIONS: In patients with MI and IGT, high plasma BNP levels predicted the occurrence of coronary stenosis, recurrent MI, and worsening of HF, whereas diuretic use did not predict the progression of coronary stenosis but non-fatal MI and worsening of HF.

Arterial stiffening is a crucial factor for left ventricular diastolic dysfunction in a community-based normotensive population.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is an important underlying hemodynamic mechanism for heart failure. Hypertension reportedly increases aortic stiffness with histological changes in the aorta assessed using aortic pulse wave velocity (PWV) that is associated with LV diastolic dysfunction. The role of hypertension per se in the relationship between aortic stiffness and LV diastolic dysfunction has not been clarified; therefore, we investigated whether this relation works for normotensive subjects. METHODS: Of the 502 subjects who underwent both echocardiography and PWV measurement in a medical check-up conducted in Arita, Japan, we enrolled 262 consecutive normotensive subjects (age 52 ± 13 years). LV diastolic dysfunction was defined as abnormal relaxation and pseudonormal or restrictive patterns determined with both transmitral flow velocity and mitral annular velocity. Aortic stiffness was assessed via non-invasive brachial-ankle PWV measurement. RESULTS: LV diastolic dysfunction was detected in 67 of the 262 (26%) normotensive subjects, and PWV was higher in subjects with LV diastolic dysfunction (15.4 ± 3.6 vs. 13.0 ± 2.7 m/s, p < 0.01). Multivariate logistic regression analyses revealed that PWV was independently associated with LV diastolic dysfunction (p = 0.02) after the adjustment for age; body mass index; blood pressure; eGFR; blood levels of BNP, glucose, and HDL cholesterol; LV mass index; and LA dimension. CONCLUSIONS: Both aortic stiffness and LV diastolic function are mutually related even in normotensive subjects, independent of the potential confounding factors. The increase in aortic stiffness may be a risk factor for LV diastolic dysfunction, irrespective of blood pressure.

The impact of creating mathematical formula to predict cardiovascular events in patients with heart failure.

Since our retrospective study has formed a mathematical formula, α = f(x1, …, x252), where α is the probability of cardiovascular events in patients with heart failure (HF) and x1 is each clinical parameter, we prospectively tested the predictive capability and feasibility of the mathematical formula of cardiovascular events in HF patients. First of all, to create such a mathematical formula using limited number of the parameters to predict the cardiovascular events in HF patients, we retrospectively determined f(x) that formulates the relationship between the most influential 50 clinical parameters (x) among 252 parameters using 167 patients hospitalized due to acute HF; the nonlinear optimization could provide the formula of α = f(x1, …, x50) which fitted the probability of the actual cardiovascular events per day. Secondly, we prospectively examined the predictability of f(x) in other 213 patients using 50 clinical parameters in 3 hospitals, and we found that the Kaplan-Meier curves using actual and estimated occurrence probabilities of cardiovascular events were closely correlated. We conclude that we created a mathematical formula f(x) that precisely predicted the occurrence probability of future cardiovascular outcomes of HF patients per day. Mathematical modelling may predict the occurrence probability of cardiovascular events in HF patients.

Cardiovascular Outcomes in Patients With Previous Myocardial Infarction and Mild Diabetes Mellitus Following Treatment With Pioglitazone: Reports of a Randomised Trial From The Japan Working Group for the Assessment Whether Pioglitazone Protects DM Patients Against Re-Infarction (PPAR Study).

BACKGROUND: Secondary prevention in patients with myocardial infarction (MI) is critically important to prevent ischaemic heart failure and reduce social burden. Pioglitazone improves vascular dysfunction and prevents coronary atherosclerosis, mainly via anti-inflammatory and antiatherogenic effects by enhancing adiponectin production in addition to antihyperglycemic effects, thus suggesting that pioglitazone attenuates cardiovascular events in patients with mild (HbA1c levels < 6·5%) diabetes mellitus (DM). Therefore, we evaluated the effects of pioglitazone on cardiovascular events in patients with both previous MI and mild DM. METHODS: In this multicentre, prospective, randomised, open, blinded-endpoint trial, we randomly assigned 630 patients with mild DM with a history of MI to undergo either DM therapy with (pioglitazone group) or without (control group) pioglitazone. DM was diagnosed using the 75-g oral glucose tolerance test, and mild DM was defined if HbA1c level was < 6·5%. The primary endpoint was the composite of cardiovascular death and hospitalisation caused by acute MI, unstable angina, coronary revascularisation (including percutaneous coronary intervention and cardiac bypass surgery), and stroke. FINDINGS: HbA1C levels were 5·9 and 5·8% (p = 0·71) at baseline and 6·0 and 5·8% (p < 0·01) at 2 years for the control and pioglitazone groups, respectively.The primary endpoint was observed in 14·2% and 14·1% patients in the control and pioglitazone groups during two years (95% confidential interval (CI):0.662-1·526, p = 0·98), respectively; the incidence of MI and cerebral infarction was 0·3% and 2·2% (95%CI: 0·786-32·415, p = 0·09) and 1·0% and 0·3% (95%CI: 0·051-3·662, p = 0·44), respectively. Post-hoc analyses of the 7-year observation period showed that these trends were comparable (21·9% and 19·2% in the control and pioglitazone groups, 95%CI: 0.618-1·237, p = 0·45). INTERPRETATION: Pioglitazone could not reduce the occurrence of cardiovascular events in patients with mild DM and previous MI.

Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?

PURPOSE: We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). METHODS: This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. RESULTS: The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints. CONCLUSION: Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00212017.

Plasma B-type natriuretic peptide is a useful tool for assessing coronary heart disease risk in a Japanese general population.

B-type natriuretic peptide (BNP) has been reported to be associated with cardiovascular prognosis in a community-based population. In addition, accumulation of individual cardiovascular risk factors is important in predicting an individual's risk of future cardiovascular disease. However, there have been few reports showing that BNP is a comprehensive marker of the accumulation of cardiovascular risk factors. We studied 1530 community-dwelling subjects without obvious heart diseases or renal dysfunction (mean age 62 ± 15 years; 569 men and 961 women) who participated in an annual health checkup in a rural Japanese community. Coronary heart disease (CHD) risk was estimated, and patients were placed into the following three groups based on the Framingham function: low risk, moderate risk and high risk. The prevalence of moderate- and high-risk subjects for CHD rose in both genders with increasing plasma BNP levels. The area under the receiver operating characteristic curve showed a modest ability of plasma BNP levels to detect these subjects (0.755 and 0.700 for men and women, respectively). The optimal thresholds for the identification of subjects with moderate- and high-risk disease were BNP concentrations of 12.0 and 22.0 pg ml(-1), with sensitivities of 70% and 66% and specificities of 71% and 63% for men and women, respectively. In conclusion, subjects with high plasma BNP levels were at higher risk for CHD in a population without obvious heart disease or renal dysfunction.

Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts: role of NO.

Carperitide is effective for heart failure (HF) owing to its diuretic and vasodilatory effects. This recombinant peptide may also have direct cardioprotective effects because carperitide reduces the severity of heart failure and limits infarct size. Because coronary vasodilation is an important cardioprotective treatment modality, we investigated whether carperitide increased coronary blood flow (CBF) and improved myocardial metabolic and contractile dysfunction during ischemia in canine hearts. We also tested whether carperitide is directly responsible for limiting the infarct size. We infused carperitide at 0.025-0.2 µg kg(-1) min(-1) into the canine coronary artery. A minimum dose of 0.1 µg kg(-1) min(-1) was required to obtain maximal vasodilation. To test the effects of carperitide on ischemic hearts, we reduced perfusion pressure in the left anterior descending coronary artery such that CBF decreased to one-third of the baseline value. At 10 min after carperitide was infused at a dose of 0.1 µg kg(-1) min(-1), we observed increases in CBF, fractional shortening (FS) and pH levels in coronary venous blood without concomitant increases in cardiac nitric oxide (NO) levels; these changes were attenuated using either the atrial natriuretic peptide receptor antagonist HS-142-1 or the NO synthase inhibitor L(ω)-nitroarginine methyl ester (L-NAME). Cyclic guanosine monophosphate (GMP) levels in the coronary artery were elevated in response to carperitide that also limited the infarct size after 90 min of ischemia and subsequent reperfusion. Again, these effects were blunted by L-NAME. Carperitide increases CBF, reduces myocardial contractile and metabolic dysfunction and limits infarct size. In addition, NO is necessary for carperitide-induced vasodilation and cardioprotection in ischemic hearts.

Serum blood urea nitrogen and plasma brain natriuretic Peptide and low diastolic blood pressure predict cardiovascular morbidity and mortality following discharge in acute decompensated heart failure patients.

BACKGROUND: Patients with heart failure (HF) have a high risk of cardiovascular (CV) death and re-hospitalization. The purpose of the present study was therefore to investigate predictors of CV death and re-hospitalization for acute decompensated HF (ADHF). METHODS AND RESULTS: A total of 225 patients aged 67.2±15.2 years, including 134 men (59.6%), who were hospitalized for ADHF between 2008 and 2009, were followed up. After discharge, the relationship between clinical parameters and CV events (ie, CV death or re-hospitalization for HF) was examined. Follow-up was continued until 30 April 2011. The most important predictors of re-hospitalization were serum blood urea nitrogen (BUN; adjusted hazard ratio [HR], 1.02; 95% confidence interval [CI]: 1.00-1.03, P=0.01), plasma brain natriuretic peptide (BNP; adjusted HR, 1.85; 95% CI: 1.12-3.04, P=0.02), and diastolic blood pressure (DBP; adjusted HR, 0.97; 95% CI: 0.94-1.00, P=0.049). The only predictor of CV mortality was a high BUN (adjusted HR, 1.05; 95% CI: 1.01-1.09, P=0.01). CONCLUSIONS: High serum BUN (≥22.5mg/dl), high plasma BNP (≥250pg/ml), and low DBP (<60mmHg) predict CV events in patients hospitalized for ADHF. These factors may identify high-risk patients for CV events and provide therapeutic targets for managing HF. (Circ J 2012; 76: 2372-2379).

Plasma adiponectin levels predict cardiovascular events in the observational Arita Cohort Study in Japan: the importance of the plasma adiponectin levels.

As the plasma level of adiponectin is related to metabolic syndrome and cardiovascular events, a low plasma adiponectin level may either cause or trigger cardiovascular disorders. The purpose of this study was to determine whether a low adiponectin level contributes to cardiovascular events, and to investigate the factors influencing adiponectin in the Japanese Arita-cho cohort study.We followed about 2000 subjects in Arita-cho, Saga, Japan as a cohort study, and we enrolled 637 subjects (205 men; 65.1±8.3 years old) who participated in annual health checks from 2005 to 2008 and underwent measurement of the plasma adiponectin level and an oral glucose tolerance test. We monitored the incidence of cardiovascular or cerebrovascular events in these subjects until the end of 2010, discontinuing follow-up at 3 years after the start of enrollment. Subjects with low plasma adiponectin levels (<10.5 ng ml(-1)) had a higher incidence of newly diagnosed cardiovascular diseases such as acute heart failure or acute myocardial infarction than those with high plasma adiponectin levels (≥10.5 ng ml(-1)) over an average of 2.95 years of follow-up. Multivariate analysis showed that the adiponectin level was predicted by the following parameters in all subjects: age (ß=0.16), male gender (ß=-0.267), homeostasis model assessment of insulin resistance (ß=-0.140) and the plasma levels of high-density lipoprotein cholesterol (ß=0.104), uric acid (ß=-0.13), triglycerides (ß=-0.169) and brain natriuretic peptide (ß=0.151). The difference in plasma glucose before and 120 min after the intake of a 75-g glucose load did not influence the plasma adiponectin level. The plasma adiponectin level is useful for predicting cardiovascular events, and is a measure of the risk of lifestyle-related diseases.

A histamine H2 receptor blocker ameliorates development of heart failure in dogs independently of ß-adrenergic receptor blockade.

Histamine has a positive inotropic effect on ventricular myocardium and stimulation of histamine H2 receptors increases the intracellular cAMP level via Gs protein, as dose stimulation of ß-adrenergic receptors, and worsens heart failure. To test whether a histamine H2 receptor blocker had a beneficial effect in addition to ß-adrenergic receptor blockade, we investigated the cardioprotective effect of famotidine, a histamine H2 receptor blocker, in dogs receiving a ß-blocker. We induced heart failure in dogs by rapid ventricular pacing (230 beats/min). Animals received no drugs (control group), famotidine (1 mg/kg daily), carvedilol (0.1 mg/kg daily), or carvedilol plus famotidine. Both cardiac catheterization and echocardiography were performed before and 4 weeks after the initiation of pacing. Immunohistochemical studies showed the appearance of mast cells and histamine in the myocardium after 4 weeks of pacing. In the control group, the left ventricular ejection fraction (LVEF) was decreased after 4 weeks compared with before pacing (71 ± 2 vs. 27 ± 2%, p < 0.05) and mean pulmonary capillary wedge pressure (PCWP) was increased (8 ± 1 vs. 19 ± 3 mmHg). Famotidine ameliorated the decrease of LVEF and increase of PCWP, while the combination of carvedilol plus famotidine further improved both parameters compared with the carvedilol groups. These beneficial effects of famotidine were associated with a decrease of the myocardial cAMP level. Histamine H2 receptor blockade preserves cardiac systolic function in dogs with pacing-induced heart failure, even in the presence of ß-adrenergic receptor blockade. This finding strengthens the rationale for using histamine H2 blockers in the treatment of heart failure.

[Anti-diabetic drugs for secondary prevention of cardiovascular disease in mild diabetic and IGT patients: ABC study and PPAR study].

A variety of epidemiological researches culminated in the fact that patients with diabetes mellitus (DM) are at high risk of cardiovascular diseases including myocardial infarction. Recently, observational researches showed that impaired glucose tolerance (IGT) is also a risk factor for cardiovascular disease, and STOP-NIDDM study demonstrated that the treatment of IGT patients with acarbose reduced the risk of cardiovascular events as well as the progression to diabetes mellitus. However, there are no reports on the secondary prevention of anti-diabetic drugs for cardiovascular disease in IGT patients. To this end, we are conducting two clinical studies: PPAR Study and ABC Study, and the results of these studies are expected to establish the involvement of metabolic disorders in cardiovascular medicine.

Left atrial volume combined with atrial pump function identifies hypertensive patients with a history of paroxysmal atrial fibrillation.

Identifying patients at high risk for the occurrence of atrial fibrillation is one means by which subsequent thromboembolic complications may be prevented. Left atrial enlargement is associated with progression of atrial remodeling, which is a substrate for atrial fibrillation, but impaired atrial pump function is also another aspect of the remodeling. Our objective was to differentiate patients with a history of paroxysmal atrial fibrillation using echocardiography. We studied 280 hypertensive patients (age: 66+/-7 years; left ventricular ejection fraction: 65+/-8%), including 140 consecutive patients with paroxysmal atrial fibrillation and 140 age- and sex-matched control subjects. Left atrial volume was measured using the modified Simpson method at both left ventricular end systole and preatrial contraction and was indexed to body surface area. Peak late-diastolic mitral annular velocity was measured during atrial contraction using pulsed tissue Doppler imaging as an atrial pump function. Left atrial volume index measured at left ventricular end systole had a 74% diagnostic accuracy and a 71% positive predictive value for identifying patients with paroxysmal atrial fibrillation; these values for the ratio of left atrial volume index at left ventricular end systole to the peak late-diastolic mitral annular velocity were 82% and 81%, respectively, and those for the ratio of left atrial volume index at preatrial contraction to the peak late-diastolic mitral annular velocity were 86% and 90%, respectively. In conclusion, left atrial size combined with atrial pump function enabled a more accurate diagnosis of a history of paroxysmal atrial fibrillation than conventional parameters.

Risk factors for chronic kidney disease in Japan: a community-based study.

BACKGROUND: Chronic kidney disease (CKD) is increasingly being recognized as a predictor for both end-stage renal disease and cardiovascular disease. The present study, conducted on individuals from a community in Arita, Japan, was designed to evaluate biomarkers that can be used to determine the associated factors for CKD. METHODS: This study involved 1554 individuals. Kidney function was evaluated in terms of the creatinine-based estimated glomerular filtration rate (eGFR), which was determined using the Modification of Diet in Renal Disease equation. Low eGFR was defined as eGFR < 60 mL/min per 1.73 m2. The concentration of both urinary albumin and urinary type IV collagen were measured. RESULTS: In the younger participants (age, <65 years), the odds ratio (95% confidence interval [CI]) of low eGFR was 1.17 (1.02 to 1.34) for each 1 year older age, 6.28 (1.41 to 28.03) for urinary albumin creatinine ratio (ACR) over 17.9 mg/g and 9.43 (2.55 to 34.91) for hyperlipidemia. On the other hand, among the elderly participants (age, > or = 65 years), the odds ratio (95% CI) of low eGFR was 2.97 (1.33 to 6.62) for gender, 1.62 (1.06 to 2.50) for hypertension and 1.97 (1.19 to 3.28) for hyperlipidemia. Urinary type IV collagen creatinine ratio was not identified as an associated factor for low eGFR. CONCLUSION: In this present cross-sectional community-based study, ACR is associated with CKD, which was defined as an eGFR of less than 60 mL/min per 1.73 m2, in the younger participants but not in the older participants.

Transient constrictive pericarditis diagnosed by cardiac magnetic resonance, 67Ga scintigraphy, and positron emission tomography.

Constrictive pericarditis occurs following pericardial fibrosis and often leads to refractory right side heart failure. Surgical relief is often required for correction of hemodynamic abnormalities. Two recent reports described a transient form of constrictive pericarditis that resolved without surgical intervention. In this case, we present representative images of transient constrictive pericarditis detected by late gadolinium enhancement of cardiac magnetic resonance, 67Ga scintigraphy, and 18FDG positron emission tomography before and after corticosteroid therapy. This is the first demonstration of the utility of imaging modalities in the diagnosis of transient constrictive pericarditis, and we document radiologic changes in pericardial inflammation after medical therapy.

Metformin prevents progression of heart failure in dogs: role of AMP-activated protein kinase.

BACKGROUND: Some studies have shown that metformin activates AMP-activated protein kinase (AMPK) and has a potent cardioprotective effect against ischemia/reperfusion injury. Because AMPK also is activated in animal models of heart failure, we investigated whether metformin decreases cardiomyocyte apoptosis and attenuates the progression of heart failure in dogs. METHODS AND RESULTS: Treatment with metformin (10 micromol/L) protected cultured cardiomyocytes from cell death during exposure to H2O2 (50 micromol/L) via AMPK activation, as shown by the MTT assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, and flow cytometry. Continuous rapid ventricular pacing (230 bpm for 4 weeks) caused typical heart failure in dogs. Both left ventricular fractional shortening and left ventricular end-diastolic pressure were significantly improved in dogs treated with oral metformin at 100 mg x kg(-1) x d(-1) (n=8) (18.6+/-1.8% and 11.8+/-1.1 mm Hg, respectively) compared with dogs receiving vehicle (n=8) (9.6+/-0.7% and 22+/-0.9 mm Hg, respectively). Metformin also promoted phosphorylation of both AMPK and endothelial nitric oxide synthase, increased plasma nitric oxide levels, and improved insulin resistance. As a result of these effects, metformin decreased apoptosis and improved cardiac function in failing canine hearts. Interestingly, another AMPK activator (AICAR) had effects equivalent to those of metformin, suggesting the primary role of AMPK activation in reducing apoptosis and preventing heart failure. CONCLUSIONS: Metformin attenuated oxidative stress-induced cardiomyocyte apoptosis and prevented the progression of heart failure in dogs, along with activation of AMPK. Therefore, metformin may be a potential new therapy for heart failure.

Prolonged targeting of ischemic/reperfused myocardium by liposomal adenosine augments cardioprotection in rats.

OBJECTIVES: The purpose of this study was to investigate whether liposomal adenosine has stronger cardioprotective effects and fewer side effects than free adenosine. BACKGROUND: Liposomes are nanoparticles that can deliver various agents to target tissues and delay degradation of these agents. Liposomes coated with polyethylene glycol (PEG) prolong the residence time of drugs in the blood. Although adenosine reduces the myocardial infarct (MI) size in clinical trials, it also causes hypotension and bradycardia. METHODS: We prepared PEGylated liposomal adenosine (mean diameter 134 +/- 21 nm) by the hydration method. In rats, we evaluated the myocardial accumulation of liposomes and MI size at 3 h after 30 min of ischemia followed by reperfusion. RESULTS: The electron microscopy and ex vivo bioluminescence imaging showed the specific accumulation of liposomes in ischemic/reperfused myocardium. Investigation of radioisotope-labeled adenosine encapsulated in PEGylated liposomes revealed a prolonged blood residence time. An intravenous infusion of PEGylated liposomal adenosine (450 microg/kg/min) had a weaker effect on blood pressure and heart rate than the corresponding dose of free adenosine. An intravenous infusion of PEGylated liposomal adenosine (450 microg/kg/min) for 10 min from 5 min before the onset of reperfusion significantly reduced MI size (29.5 +/- 6.5%) compared with an infusion of saline (53.2 +/- 3.5%, p < 0.05). The antagonist of adenosine A(1), A(2a), A(2b), or A(3) subtype receptor blocked cardioprotection observed in the PEGylated liposomal adenosine-treated group. CONCLUSIONS: An infusion as PEGylated liposomes augmented the cardioprotective effects of adenosine against ischemia/reperfusion injury and reduced its unfavorable hemodynamic effects. Liposomes are promising for developing new treatments for acute MI.

Dobutamine stress echocardiography unmasks acute worsening of mitral regurgitation with latent left ventricular outflow tract obstruction behind diastolic heart failure in hypertensive heart disease.

In a 57-year-old woman who was referred as refractory diastolic heart failure, dobutamine stress echocardiography facilitated the diagnosis of acute worsening of mitral regurgitation accompanied with latent left ventricular outflow tract obstruction as a cause of recurrent flash pulmonary edema. Echocardiography revealed the presence of sigmoid septum and concentric left ventricular hypertrophy, being consistent with hypertensive heart disease. Dobutamine induced systolic anterior motion of the mitral valve (SAM) with massive mitral regurgitation, resulting in sudden hypotension with dyspnea. The class Ia antiarrhythmic drug, cibenzoline, reduced the SAM during a dobutamine stress test, followed by no recurrence of flash pulmonary edema.