Exploring the Multifaceted Nexus of Uric Acid and Health: A Review of Recent Studies on Diverse Diseases.

The prevalence of patients with hyperuricemia or gout is increasing worldwide. Hyperuricemia and gout are primarily attributed to genetic factors, along with lifestyle factors like consuming a purine-rich diet, alcohol and/or fructose intake, and physical activity. While numerous studies have reported various comorbidities linked to hyperuricemia or gout, the range of these associations is extensive. This review article focuses on the relationship between uric acid and thirteen specific domains: transporters, genetic factors, diet, lifestyle, gout, diabetes mellitus, metabolic syndrome, atherosclerosis, hypertension, kidney diseases, cardiovascular diseases, neurological diseases, and malignancies. The present article provides a comprehensive review of recent developments in these areas, compiled by experts from the Young Committee of the Japanese Society of Gout and Uric and Nucleic Acids. The consolidated summary serves to enhance the global comprehension of uric acid-related matters.

Annual Increase of Acute Inpatients with Both Cancer and Cardiovascular Diseases in Japan 2011-2015: Analysis From National Database of Health Insurance Claims and Specific Health Checkups of Japan.

BACKGROUND: Patients with cancer were able to live longer due to improvements in cancer treatment. Additionally, cardiovascular disease (CVD) is the second leading cause of mortality in cancer survivors. However, epidemiological data on onco-CVD have not been sufficiently provided. We aimed to investigate the clinical characteristics of cancer in CVD patients using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). METHOD AND RESULTS: The NDB sampling dataset used in this study was randomly sampled 10% from the whole Diagnosis Procedure Combination (DPC) records from every January, April, July, and October from 2011 to 2015. The significance of the increase trend in the percentage of records in each disease group to the total number of all DPC records from 2011 to 2015 was checked with Chi-square test with a Bonferroni correction. The percentage of records in cancer with the CVD group to the total number of all DPC records significantly increased over time, and their average age also increased since 2011. Their proportion over 75 years was approximately 56 % in 2015. There was no difference in the cancer sites. However, the prevalence of heart failure dramatically elevated. CONCLUSION: We were able to assess the increase in cancer among CVD patients using DPC inpatient records obtained from the NDB. Both cardiologists and oncologists should be more aware of this phenomenon.

Cardiovascular adverse events and prognosis in patients with haematologic malignancies and breast cancer receiving anticancer agents: Kurume-CREO Registry insights.

AIMS: Cancer treatment-related cardiovascular toxicity (CTR-CVT) is a growing concern in patients undergoing anticancer therapy. The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) risk assessment tools have been proposed for the baseline cardiovascular (CV) risk stratification of patients with cancer. This study investigated the incidence of CV adverse events in clinical practice, also using the HFA-ICOS risk tool. METHODS AND RESULTS: This single-centre, prospective, observational study was conducted at Kurume University Hospital from October 2016 to August 2021, including patients aged ≥20 years with haematologic malignancies or breast cancer who were receiving anticancer agents. Cardiovascular assessments were performed at enrolment and every 6 months until August 2021, with additional assessments for suspected CV adverse events. The primary endpoint was common terminology criteria for adverse events v4.0 Grade ≥2, and the secondary endpoints were all-cause and CV deaths. Of the enrolled 486 patients, CV adverse events occurred in 24.5, 15.8, 38.1, and 18.0% of patients with leukaemia, malignant lymphoma, multiple myeloma, and breast cancer, respectively. Patients at high or very high risk had a significantly higher incidence of CV events, according to the HFA-ICOS risk tool. Cardiovascular death occurred in 4 (0.8%) patients during follow-up. CONCLUSION: This study revealed that 16-38% of patients with haematologic malignancies and breast cancer developed CTR-CVT during follow-up, in which patients with high/very high risk were well predicted by the HFA-ICOS risk assessment tool. Monitoring and managing CV risk factors are essential for safe cancer therapy.

As the elderly population grows worldwide, cancer and cardiac diseases have become the leading causes of death in many countries, including Japan. With advances in cancer treatment, survival rates have improved, resulting in an increasing number of cancer survivors developing therapy-related cardiovascular (CV) problems. The study, conducted at Kurume University Hospital, examined 486 participants with haematologic malignancies and breast cancer. The result demonstrates CV adverse events in 12, 45, 24, and 16 patients with leukaemia, malignant lymphoma, multiple myeloma, and breast cancer, respectively. Heart failure and left ventricular systolic dysfunction were the most common adverse events. This study demonstrates the importance of monitoring patients with cancer for potential CV risks and highlights the need for further research to improve treatment protocols for those at higher risk. Key findings include This prospective study conducted in Japan revealed a high incidence of adverse cardiovascular (CV) events in patients with haematologic malignancies and breast cancer treated with anticancer agents but a low CV mortality rate during the mid-term follow-up period. Patients at high/very high risk, as determined by the Heart Failure Association-International Cardio-Oncology Society risk assessment tool, experienced a higher incidence of CV events and heart failure compared with those at low and moderate risks.

Role of Quantitation of Saline Bubble Studies in Patients with Liver Cirrhosis.

OBJECTIVE: Microbubble contrast echocardiography with a late positive signal enables the detection of intrapulmonary vascular dilation, including hepatopulmonary syndrome, in patients with end-stage liver disease. We assessed the relationship between the severity of bubble study and clinical outcome. METHODS: We retrospectively analyzed 163 consecutive patients with liver cirrhosis who underwent an echocardiogram with bubble study from 2018 to 2021. Patients who were diagnosed with a late positive signal were divided into three groups: grade 1 (1-9 bubbles), grade 2 (10-30 bubbles) and grade 3 (>30 bubbles). RESULTS: Fifty-six percent of the patients had a late positive bubble study (grade 1: 31%, grade 2: 23%, grade 3: 46%). Patients with grade 3 had a significantly higher international normalized ratio, model for end-stage liver disease score and Child-Pugh score and a lower peripheral oxygen saturation compared with patients with a negative study. In patients undergoing liver transplant (LT), survival rates were similar among the groups (3-mo: >87%, 1-y: >87%, 2-y: >83%). However, survival rate was lower in grade 3 patients without LT (3-mo: 81%, 1-y: 64%, 2-y: 39%). CONCLUSION: Patients with grade 3 had much worse mortality without LT compared with other groups. However, after LT, all grades had equal survival. Therefore, patients with grade 3 may be considered as higher priority for LT.

A J-shaped Relationship between Sleep Duration and the Risk of Insulin Resistance in a General Japanese Population.

Objective Data on the role of sleep in the risk of insulin resistance (IR) are lacking. We therefore examined the association between sleep duration and IR in a general Japanese population. Methods Data of 1,344 individuals 34 to 89 years old from the Tanushimaru Study were analysed. IR was calculated using the fasting plasma glucose level×fasting insulin level/405, i.e. the homeostasis model assessment of IR (HOMA-IR). IR was defined as a HOMA-IR ≥1.73 based on the diagnostic criteria used in Japan. Information regarding sleep duration was collected via questionnaire. Results The frequencies of IR and metabolic syndrome (MetS) were 36.7% and 26.9%, respectively. A J-shaped relationship between sleep duration and IR was observed, and the same relationship was also shown between sleep duration and MetS; however, the relationship with MetS disappeared after adjusting for age, sex, and other confounding factors. Conclusion A J-shaped relationship was observed between sleep duration and the risks of IR in a general Japanese population.

Improvement of physical activity significantly reduced serum hepatocyte growth factor levels in a general population: 10 year prospective study.

Hepatocyte growth factor (HGF) is an adipocytokine elevated in obese subjects. We have previously reported that serum HGF levels were significantly associated with insulin resistance or components of the metabolic syndrome. However, it has been unknown how physical activity (PA) affects HGF levels after a long-term follow-up. Our aim was to clarify the association between PA changes and HGF levels as well as cerebro-cardiovascular disease (CVD) development, during a 10 year follow-up period in a Japanese general population. Of 1320 subjects who received a health check-up examination in Tanushimaru town in 1999, 903 subjects (341 males and 562 females), who received the examination both in 1999 and 2009 were enrolled. We evaluated their PA levels by Baecke questionnaire in 1999 and by a simple questionnaire in 2009. We measured the HGF levels by ELISA method in 1999 and 2009. We divided the subjects into four PA groups, stable low PA, increased PA, decreased PA, and stable high PA. Using these questionnaires, we compared their PA and HGF levels after an interval of 10 years. A significant inverse association was found between PA changes and HGF levels at 10 years, after adjustment for age and sex. The HGF levels of the increased PA group were significantly lower than stable low PA (p = 0.038), and the increased PA group showed reduced CVD development compared to the stable low PA group after adjustment for age and sex (p = 0.012). Our data demonstrated that improvement of PA levels was associated with reduced HGF levels and CVD development.

Use of Anti-Thrombotic Drugs and In-Hospital Mortality in Acute Aortic Dissection Patients.

Acute aortic dissection occurs due to a primary tear in the aortic intima, with blood from the aortic lumen entering the adjacent diseased media. In the clinical setting, practitioners often hesitate before the use of anti-thrombotic drugs in the acute phase of aortic dissection. Therefore, we examined the clinical course in patients who had already received antithrombotic therapies at the onset of acute aortic dissection, and who were given anti-thrombotic drugs in the acute phase during hospitalization. We retrospectively enrolled 685 consecutive patients with acute aortic dissection (type A/B: 454/231), who were transferred to Kurume University Hospital from 2004 to 2020. In types A and B, there were no significant differences between in-hospital mortality with or without antithrombotic therapies at the onset (14.3% vs. 16.4%, p = 0.66 in type A, 2.6% vs. 7.3%, p = 0.29 in type B). Patients in type A who survived more than a day and were treated with anti-thrombotic drugs during hospitalization had significantly lower in-hospital mortality compared with those who received no anti-thrombotic drugs in the acute phase (2.2% vs. 16.1%, p < 0.001), while there was no significant difference between in-hospital mortality in the two type-B groups (2.4% vs. 4.9%, p = 0.48). Although there were variations in response among patients with acute aortic dissection, anti-thrombotic drugs did not worsen in-hospital mortality for patients with acute aortic dissection, indicating that medical staff should not hesitate to administer anti-thrombotic drugs if indicated.

Correlation between estimated plasma remnant-like particle cholesterol and vegetable fat intake in Uku town, Japan.

BACKGROUND: Remnant-like particle cholesterol (RLP-C) is highly atherogenic, which is associated with atherosclerosis. However, RLP-C has not been routinely measured in the clinical practice. We estimated RLP-C levels using conventional lipid profiles and examined the association between estimated RLP-C and related factors including nutrient intake. METHODS: This study was performed in Uku town, Nagasaki prefecture, Japan in 2019. A total of 225 subjects were enrolled and directly measured RLP-C levels. Estimated RLP-C levels were defined as the following formula [total cholesterol - (LDL-cholesterol) - (HDL-cholesterol)]. Multivariate analyses were used to assess the relationship between estimated RLP-C and atherogenic factors. We calculated cut-off values on dichotomized RLP-C (< 7.5 mg/dL vs. ≥ 7.5 mg/dL) by receiver operating characteristic (ROC) curve. RESULTS: The mean values of directly measured RLP-C levels and estimated RLP-C were 4.0 mg/dL and 16.4 mg/dL, respectively. In the multiple stepwise linear regression analysis, directly measured and estimated RLP-C levels were independently and commonly associated with apolipoprotein E, triglycerides, and vegetable fat intake (inversely). Using ROC curves, we found the cut-off value of estimated RLP-C was 22.0 mg/dL. CONCLUSION: We demonstrated that the estimated RLP-C levels using conventional lipid profiles may substitute for directly measured RLP-C and these levels were independently and inversely associated with vegetable fat intake in the community-dwelling Japanese population.

Serum Urate Trajectory in Young Adulthood and Incident Cardiovascular Disease Events by Middle Age: CARDIA Study.

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Optimal Quantification of Functional Mitral Regurgitation: Comparison of Volumetric and Proximal Isovelocity Surface Area Methods to Predict Outcome.

Background Effective orifice area (EOA) ≥0.2 cm2 or regurgitant volume (Rvol) ≥30 mL predicts prognostic significance in functional mitral regurgitation (FMR). Both volumetric and proximal isovelocity surface area (PISA) methods enable calculation of these metrics. To determine their clinical value, we compared EOA and Rvol derived by volumetric and PISA quantitation upon outcome of patients with FMR. Methods and Results We examined the outcome of patients with left ventricular ejection fraction <35% and moderate to severe FMR. All had a complete echocardiogram including EOA and Rvol by both standard PISA and volumetric quantitation using total stroke volume calculated by left ventricular end-diastolic volume×left ventricular ejection fraction and forward flow by Doppler method: EOA=Rvol/mitral regurgitation velocity time integral. Primary outcome was all-cause mortality or heart transplantation. We examined 177 patients: mean left ventricular ejection fraction 25.2% and 34.5% with ischemic cardiomyopathy. Echo measurements were greater by PISA than volumetric quantitation: EOA (0.18 versus 0.11 cm2), Rvol (24.7 versus 16.9 mL), and regurgitant fraction (61 versus 37 %) respectively (all P value <0.001). During 3.6±2.3 years' follow-up, patients with EOA ≥0.2 cm2 or Rvol ≥30 mL had a worse outcome than those with EOA <0.2 cm2 or Rvol <30 mL only by volumetric (log rank P=0.003 and 0.004) but not PISA quantitation (log rank P=0.984 and 0.544), respectively. Conclusions Volumetric and PISA methods yield different measurements of EOA and Rvol in FMR; volumetric values exhibit greater prognostic significance. The echo method of quantifying FMR may affect the management of this disorder.

Differential impacts of 24 hour urinary sodium excretion on cardiovascular diseases or cancer mortality in a general population.

BACKGROUND: Elevated blood pressure is a major risk factor for cardiovascular (CV) disease. But the effects of sodium intake or excretion on CV mortality are uncertain. The present study aimed to investigate the association between 24 h urinary sodium excretion, as a marker of dietary salt intake, and CV or cancer mortality in a healthy Japanese population using 24 hurine collection. METHODS: The baseline study was conducted in 1980. A total of 1291 participants aged 21 to 85 years, underwent health check-ups, which included blood chemistry measurements and the collection of 24 h urine samples. Enrolled 1291 participants were followed up for 27.5 years, in whom the final follow-up rate was 95.8%. Cox proportional hazards regression models were used to assess the association between 24 h urinary sodium excretion and CV or cancer mortality. RESULTS: The mean 24 h urinary sodium excretion was 5.80 ± 2.28 g/day. There were 631 deaths: 153 (27%) from cancer, 142 (26%) from CV disease. In the Cox proportional hazard regression model after adjustment for confounding factors, systolic and diastolic blood pressures, and uric acid were positively associated with CV mortality, and the 24 h urinary sodium and potassium excretions were inversely associated with CV mortality (p < 0.05). On the other hand, there were no association between 24 h urinary sodium excretions and cancer mortality. We divided the urinary sodium excretions levels into quartiles. After adjustment for confounding factors, the hazard ratio of CV mortality in the highest quartile of 24 h urinary sodium excretion versus the lowest was 0.46 (p < 0.05). The cumulative survival rate for CV death was significantly decreased in the lowest quartile compared with the other higher groups. CONCLUSIONS: We found that impacts of 24 h sodium excretion on CV and cancer mortalities were much different in the general population.

Impact of combined elevations of homocysteine and asymmetric dimethylarginine on all-cause death - The Tanushimaru Study.

BACKGROUND: Both homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) induce endothelial dysfunction. However, the impact of both elevations on all-cause death is not known. We investigated the association between elevations of Hcy or ADMA and all-cause death in a general population. METHODS: A total of 517 subjects (224 men, 293 women; mean age, 62.8 years) were recruited from a population-based survey in 1999 in Tanushimaru, and we measured fasting plasma Hcy and ADMA levels. We followed them up for over 20 years and examined the effect on mortality using Cox proportional hazard regression model. RESULTS: The mean follow-up years were 17.7 (1.8-20.8). In this period, 182 subjects have died (35.2%). The correlation between Hcy and ADMA was high (r=0.194; p<0.001). With Cox regression analysis after adjustments for age and sex, elevated log transformed Hcy levels were significantly associated with all-cause death (p=0.028). When Hcy and ADMA levels were divided into quintiles, the hierarchical model showed the synergistic effect of Hcy and ADMA on all-cause death. CONCLUSIONS: This is the first report that we have measured Hcy and ADMA levels simultaneously in this community-dwelling Japanese, and we demonstrated that combined elevations of Hcy and ADMA had big impact on all-cause death in this epidemiological study.

Lower albumin levels are associated with frailty measures, trace elements, and an inflammation marker in a cross-sectional study in Tanushimaru.

BACKGROUND: There is little data on the association between the lower nutrition represented by serum albumin levels and related factors in a general population. The present study aimed to determine whether the albumin level positioned as some kind of biomarker with frailty measures, trace elements, and an inflammation marker. METHODS: In 2018, we performed an epidemiological survey in 1368 subjects who resided in Tanushimaru, Japan, in which we examined the blood chemistry including albumin, trace elements, hormone levels, and carotid ultrasonography. Albumin levels were categorized into 4 groups (G1 [3.2-3.9 mg/dL], G2 [4.0-4.3 mg/dL], G3 [4.4-4.6 mg/dL], and G4 [4.7-5.3 mg/dL]). The participants underwent measurements of handgrip strength and were tested by asking to walk 5 m. Their cognitive functions were evaluated by the mini-mental state examination (MMSE). RESULTS: Multiple stepwise regression analysis demonstrated that albumin levels were significantly and independently associated with age (inversely), systolic blood pressures, estimated glomerular filtration rate (eGFR), MMSE score, frailty measures (handgrip strength), an inflammation marker (high-sensitivity C-reactive protein), hormones (growth hormone (inversely) and insulin-like growth factor-1), and trace elements (calcium, magnesium, iron, and zinc), with a linear trend. CONCLUSIONS: Lower albumin levels, even in the normal range, were found to be related factors of frailty measures, trace elements, and an inflammation marker in a general population.

Serum Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is Independently Associated with Insulin Resistance, Triglycerides, Lipoprotein(a) Levels but not Low-Density Lipoprotein Cholesterol Levels in a General Population.

AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as an important regulator of low-density lipoprotein (LDL) receptor processing. Evolocumab and alirocumab are PCSK9 inhibitors; however, little is known about the association between PCSK9 levels and lipid profiles in a general population. Because PCSK9 inhibitors have LDL-C lowering effects, we investigated whether there is a positive correlation between serum PCSK9 levels and LDL-C or lipoprotein(a) [Lp(a)]. METHODS: In Uku town, 674 residents (mean age; 69.2±8.3 years) received health check-ups. The participants underwent a physical examination and blood tests, including PCSK9 and Lp(a). Serum PCSK9 and Lp(a) were measured by ELISA and Latex methods, respectively. HOMA-IR was calculated by fasting plasma glucose×insulin levels/405. RESULTS: The mean (range) of PCSK9 and Lp(a) were 211.2 (49-601) ng/mL and 60 (1-107) mg/dL, respectively. Because of a skewed distribution, the log-transformed values were used. With univariate linear regression analysis, PCSK9 levels were associated with Lp(a) (p=0.028), triglycerides (p＜0.001), and HOMA-IR (p＜0.001), but not with LDL-C (p=0.138) levels. Multiple stepwise regression analysis revealed that serum PCSK9 levels were independently associated with triglycerides (p＜0.001), Lp(a) (p=0.033) and HOMA-IR (p=0.041). CONCLUSIONS: PCSK-9 is independently associated with triglycerides, Lp(a) levels, and HOMA-IR, but not LDL-C, in a relatively large general population sample.

Association between growth hormone and hypertension in a general population.

Insulin-like growth factors are polypeptides, with arrays similar to insulin, and insulin-like growth factor 1 (IGF-1) is secreted via stimulation by growth hormone (GH) in the liver. The lack of both GH and IGF-1 leads to physiological age-related changes in the cardiovascular system; however, the role of IGF-1 and GH in hypertension has not been fully elucidated. Thus, we examined the association between plasma IGF-1 and GH levels and hypertension. Among 1368 health check-up examination participants in the town of Tanushimaru, 1094 subjects were analyzed after excluding subjects with diabetes mellitus or impaired liver function. Multiple linear and logistic regression analyses were performed for factors related to systolic and diastolic blood pressures (BPs). Characteristics of participants stratified by IGF-1 and GH quartiles were compared using analysis of covariance. We calculated odds ratios associated with each standard deviation increase in IGF-1 and GH levels for hypertension, which was defined as BP ≥ 140/90 mmHg and/or the use of antihypertensive medication. Multivariable analysis showed that FPG, insulin, HOMA-IR, eGFR, total cholesterol, triglycerides, and the use of medication for hypertension were associated with the Z-score of IGF-1 measurement quartiles. Next, we found that BMI, systolic and diastolic BPs, insulin, HOMA-IR, total cholesterol, HDL-cholesterol, triglycerides, smoking, and alcohol intake were associated with GH quartiles, indicating that hypertension was inversely associated with GH but not IGF-1. A significant and inverse relationship between serum GH and hypertension was found after adjustment for confounders. In conclusion, decreased GH but not IGF-1, was associated with hypertension in a general population.

Association between physical activity, occupational sitting time and mortality in a general population: An 18-year prospective survey in Tanushimaru, Japan.

AIMS: It is well known that a decline in physical activity is associated with an increase of all-cause death including cardiovascular events and cancer. Few studies have examined the association between occupational sitting time and mortality. Therefore, we investigated this issue in a general population. METHODS: Physical activity and occupational sitting time were measured using the Baecke physical activity questionnaire in 1999. The questionnaire generated indices in three physical activity categories: work, sport and leisure-time. A total physical activity index was calculated by adding these three indices. The Baecke physical activity questionnaire was able to evaluate occupational sitting time. Hazard ratios and 95% confidence intervals (CIs) were calculated using Cox's proportional hazard regression models. RESULTS: We enrolled a total of 1680 participants, who were followed up for 15.9 ± 3.8 years. The final follow-up rate was 93%. During the follow-up period, 397 subjects died. A significant inverse association (p < 0.0001) was found between physical activity and mortality after adjustment for age and sex. Compared with lower levels of physical activity, the adjusted hazard ratio for mortality at higher levels of physical activity was 0.85 (95% CI: 0.78-0.92). Longer occupational sitting time was also significantly associated with higher mortality (p < 0.01). The adjusted hazard ratio for mortality at longer occupational sitting time was 1.16 (95% CI: 1.05-1.27). These findings were observed in males, but not in females. CONCLUSIONS: Our data demonstrated that higher levels of physical activity are associated with a reduced risk of cancer and cardiovascular death. Further, longer occupational sitting time is associated with increased mortality.

Habitual coffee intake reduces all-cause mortality by decreasing heart rate.

It is well known that subjects with metabolic syndrome show an elevated resting heart rate. We previously reported that elevated heart rate was significantly related to all-cause mortality, and that coffee consumption was inversely associated with metabolic syndrome. We hypothesized that higher coffee consumption may decrease all-cause mortality by reducing resting heart rate. We performed a longitudinal epidemiological study in Tanushimaru (a cohort of the Seven Countries Study). A total of 1920 residents aged over 40 years received health checkups in 1999. We measured components of metabolic syndrome, and eating and drinking patterns were evaluated by a food frequency questionnaire. We followed up the participants annually for 15 years. During the follow-up period, 343 of the participants died. Of these, 102 subjects died of cancer, 48 of cerebro-cardiovascular diseases, and 44 of infectious diseases. Multivariate analyses revealed that higher coffee consumption was inversely associated with resting heart rate. Kaplan-Meier curves found lower mortality rates in the higher coffee consumption groups. In the lower coffee consumption groups, elevated hazard ratios of all-cause death were observed in the increased heart rate quintiles, whereas heart rate was not associated with all-cause death in the higher coffee consumption groups. These significant associations remained after further adjustment for confounders. This prospective study suggests that higher coffee consumption may have a protective effect against all-cause death due to reducing resting heart rate.

Thrombospondin-2 as a Potential Risk Factor in a General Population.

Serum thrombospondin-2 (TSP-2) is a glycoprotein expressed in the extracellular matrix (ECM), which increases during tissue remodeling. It has been shown in recent studies that TSP-2 is a useful predictor of cardiovascular death in patients with heart failure (HF). However, the clinical importance of serum TSP-2 levels in a general population is still unknown. Therefore, we aimed to clarify the association between TSP-2 and clinical risk factors. A periodic epidemiological survey was performed in a community dwelling in the town of Uku, Nagasaki, Japan. A total of 445 residents received a health checkup examination including blood tests such as fasting serum levels of TSP-2. Uni- and multivariate analyses were performed to examine the relationship between TSP-2 and clinical risk factors. All statistical analyses were performed using SAS v9.4 program. The mean ± standard deviation of age was 67.0 ± 9.4 years old. Although serum TSP-2 levels (mean: 20.9 ± 8.5 ng/mL) showed no significant sex difference, they were significantly correlated with the levels of plasma glucose (P < 0.001), insulin (P < 0.01), homeostasis model assessment of insulin resistance (HOMA-IR) (P < 0.001), estimated glomerular filtration rate (eGFR) (P < 0.01, inversely), high-sensitivity C-reactive protein (hs-CRP) (P < 0.001), history of atrial fibrillation (P < 0.001), history of cardiovascular diseases (P < 0.001), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (P < 0.001). Moreover, in the multiple stepwise linear regression analysis, the levels of TSP-2 were independently and significantly associated with the history of atrial fibrillation (P < 0.0001), HOMA-IR (P < 0.001), high-sensitivity CRP (P = 0.011), and NT-proBNP (P = 0.043). These results indicated the significant relationship between TSP-2 and clinical risk factors in a general population, suggesting its role as a predictor of heart disease morbidity and mortality.

The Use of Bromocriptine for Peripartum Cardiomyopathy after Twin Delivery via Oocyte Donation.

Peripartum cardiomyopathy (PPCM) is rare but life-threatening. We herein report the case of a 48-year-old woman with PPCM after oocyte donation and delivery of twins. Two weeks after delivery, she suffered from severe symptoms of heart failure [orthopnea, New York Heart Association (NYHA) class IV, pulmonary edema and a reduced left ventricular ejection fraction of 18%]. Although standard heart failure therapy was effective for diminishing the congestion, it was not sufficient to improve her symptoms or left ventricular systolic dysfunction. During admission, we added bromocriptine. A year later after the onset, she was in a good state with an improved left ventricular systolic function.

Twenty-four-Hour Urinary Potassium Excretion, But Not Sodium Excretion, Is Associated With All-Cause Mortality in a General Population.

BACKGROUND: Few studies have examined the relationship between accurate monitoring of sodium or potassium consumption and mortality. We aimed to investigate the association between 24-hour urinary sodium or potassium excretion and ≈30-year mortality in a Japanese population using 24-hour urine collection. METHODS AND RESULTS: We enrolled a total of 1291 participants, aged 21 to 85 years, who underwent health checkups, including a blood test and 24-hour urine collection. They were followed up for 27.5±9.9 years by December 31, 2015, and the final follow-up rate was 95.8%. Cox proportional hazards regression analysis was used to assess the association between 24-hour urinary sodium or potassium excretion and all-cause mortality. At baseline, the mean 24-hour urinary sodium and potassium excretions were 5.80±2.28 g/d and 1.85±0.82 g/d, respectively. There were 631 deaths during the follow-up. The cumulative survival rate was significantly decreased in the lowest quartile compared with the other higher groups. In the Cox proportional hazard model after adjustment for age and sex, 24-hour urinary potassium excretion, but not sodium excretion, was inversely associated with all-cause mortality. We divided the 24-hour urinary potassium excretion levels into quartiles. After adjustment for confounding factors, the hazard ratio of all-cause mortality in the highest quartile of 24-hour urinary potassium excretion versus the lowest was 0.62 (95% confidence interval, 0.48-0.79; P<0.001). CONCLUSIONS: The 24-hour urinary potassium excretion, but not sodium excretion, was significantly associated with all-cause mortality in the general population.