Naohito Tanabe

Body mass index and risk of stroke and myocardial infarction in a relatively lean population: meta-analysis of 16 Japanese cohorts using individual data.

Background–The association of overweight/obesity with the incidence of cardiovascular diseases, especially stroke, has not been comprehensively examined in relatively lean populations in which stroke is more prevalent than coronary heart disease. Methods and Results–Pooled individual data from 16 Japanese cohorts comprising 45 235 participants ages 40 to 89 years without previous history of cardiovascular disease were studied. During follow-up, 1113 incident strokes and 190 myocardial infarctions were identified. At baseline, mean ages of men and women were 55.4 and 56.5 years and mean body mass indices (BMI) were 23.0 and 23.4 kg/m2, respectively. Compared with those with BMI <21.0, incidence rates of cerebral infarction in subjects with BMI ≥27.5 were significantly elevated in both men (hazard ratio, 1.81; 95% confidence interval [CI], 1.28 to 2.56) and women (hazard ratio, 1.65; 95% CI, 1.23 to 2.21), adjusted for age, smoking, and drinking habit. Incidence of cerebral hemorrhage was also associated positively with BMI in both men (hazard ratio, 2.51; 95% CI, 1.21 to 5.20) and women (hazard ratio, 1.98; 95% CI, 1.12 to 3.52). Adjustment for systolic blood pressure, a mediating factor, significantly attenuated most BMI association with stroke in both sexes. For myocardial infarction, the hazard ratio was 3.16 (95% CI, 1.66 to 6.01) for BMI 27.5 or greater versus less than 21.0 only in men, which appeared partly mediated by total cholesterol and SBP. Conclusions–Overweight/obesity was associated with an increased risk of cerebral infarction and hemorrhage in men and women and myocardial infarction in men. Weight control may have the potential to prevent both stroke and myocardial infarction in Japan.

Incidence of osteoporotic fractures in Sado, Japan in 2010

We conducted a survey of fracture incidences associated with senile osteoporosis in 2010 in Sado City, Niigata Prefecture, Japan, including compression vertebral fractures, hip fractures, distal radius fractures, and fractures of the proximal end of the humerus. We previously conducted a similar survey from 2004−2006 in Sado City. The purpose of the current study was to determine the incidence of osteoporotic fractures in Sado City in 2010 and to examine changes over time. We calculated the incidence of each fracture per 100,000 person-years based on the population of Sado City. Hip and vertebral fractures showed marked increases from 2004−2006, but a similar increase was not found from 2006−2010. The average age at injury increased in 2010 compared to 2004, except for fractures of the radius. Among the subjects with hip fractures, 14xa0% had a history of contralateral hip fracture. The percentage of patients taking medication for osteoporosis before injury was higher in 2010 compared with 2004, but these percentages were still only 7 and 13xa0% for those with subsequent hip and vertebral fractures, respectively.

Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in reactive amyloidosis associated with rheumatoid arthritis

The kidney is a major target organ for systemic amyloidosis, resulting in proteinuria and an elevated serum creatinine level. In patients with reactive amyloidosis associated with rheumatoid arthritis, a correlation between the amount of amyloid deposits and clinical parameters is not known. The purpose of this study was to clarify the association between various factors including renal function and the area of amyloid deposition in these patients. Fifty-eight patients with an established diagnosis of reactive AA amyloidosis were studied. We retrospectively investigated the correlation between clinical data and the area occupied by amyloid in renal biopsy specimens. All the patients showed amyloid deposits in renal tissues, and the percentage of the area occupied by amyloid was <10% in 54 of them. Mesangial proliferative glomerulonephritis and membranous nephropathy were frequently combined with renal amyloidosis. For statistical analyses, the percentage of the area occupied by amyloid was transformed to a common logarithmic value (Log10 % amyloid), as the histograms showed a log-normal distribution. Log10 % amyloid was found to be correlated with age, creatinine (Cr) level, creatinine clearance (Ccr), blood urea nitrogen (BUN) level, and the estimated glomerular filtration rate (eGFR). Multiple linear regression analyses were then performed to examine the sex- and age-adjusted association between Log10 % amyloid and each of the clinical variables. Cr, Ccr, BUN, UA, CRP, and eGFR were significantly correlated with Log10 % amyloid, but urinary protein was not. There was a significant correlation between the area of amyloid deposition in renal tissue and parameters of renal function, especially Cr and Ccr. If amyloid deposition in renal tissue can be arrested or prevented, then it may be possible to maintain renal function at an acceptable level.

Incidence of hip fracture in Niigata, Japan in 2004 and 2010 and the long-term trends from 1985 to 2010.

We investigated the incidence of hip fracture in a population of patients ≥50xa0yearsxa0old in 2004 and 2010 in Niigata City, Niigata Prefecture, Japan. We also investigated the long-term trends in the incidence of hip fracture from 1985 to 2010, using our previously reported survey results obtained from 1985 to 1999. In 2004 and 2010, the survey found 2,368 and 3,218 proximal femur fractures, respectively. The crude hip fracture incidence rates in 2004 and 2010 were 215.8 and 281.5 per 100,000 of population per year, respectively. For males, the incidence rates were 99.9 in 2004 and 126.3 in 2010; for females, the incidence rates were 311.0 and 410.7, respectively. In males aged 80–84xa0years, the incidence rate since 1999 has been decreasing, while that for males >85xa0years peaked in 2004. In females of all ages, the incidence rate was higher in 2010 than in all other survey periods, and in females >85xa0years, the incidence has increased the fastest. Additionally, the long-term changes in the age- and sex-standardized incidence each year using the 1985 population structure in Japan in females has been increasing, although it decreased in 1999. However, in males, the incidence in 2010 was not significantly different from that in 1994, although it has been increasing since 1999. Our study findings indicate that the age-specific incidence of hip fractures in the Niigata Prefecture of Japan has not plateaued in females, but that it may have done so in males; in addition, the number and incidence of hip fractures has been increasing.

Electrocardiographic abnormalities and risk of developing cardiac events in extracardiac sarcoidosis

BACKGROUNDnCardiac involvement is a leading cause of death from sarcoidosis. Because the efficacy of corticosteroid treatment is limited in patients with cardiac manifestation, early diagnosis is important. However, cardiac involvement is difficult to identify at early stages and is often underdiagnosed. Therefore, this study aimed to identify electrocardiographic risk factors for cardiac events in patients with extracardiac sarcoidosis.nnnMETHODSnThis prospective observational cohort study included 227 patients with extracardiac sarcoidosis who did not have any cardiac manifestation (age, 49 ± 17 years; women, 63%). We studied the association of electrocardiographic abnormalities with developing cardiac manifestations.nnnRESULTSnDuring a follow-up of 6.3 ± 3.7 years, 11 patients developed cardiac events, including advanced atrioventricular block (4 patients), ventricular tachycardia (4 patients), and systolic dysfunction (3 patients). All patients had electrocardiographic abnormalities prior to the development of cardiac events. In multivariate analyses, the baseline heart rate and PR interval were associated with increased risk of developing cardiac events. The QRS duration and corrected QT interval were not associated with cardiac manifestations. The multivariate analyses also revealed that baseline conduction disorder, ST segment/T wave abnormalities, and fragmented QRS complexes were associated with cardiac events.nnnCONCLUSIONSnElectrocardiographic abnormalities occurred prior to cardiac events in extracardiac sarcoidosis. Patients with electrocardiographic abnormalities may require further evaluation for cardiac involvement and careful follow-up.

Benefits of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise on albuminuria in diabetic and non-diabetic Japanese populations

BackgroundAlbuminuria is a biomarker for chronic kidney disease and an independent predictor of cardiovascular and all-cause mortality. A recent meta-analysis concluded that these risks increase with urinary albumin concentration, even when below the microalbuminuria threshold. Thus, minimizing urinary albumin may be a valuable therapeutic goal regardless of disease status.MethodsWe investigated the benefits and safety of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise for reducing albuminuria in 295 normoalbuminuric or microalbuminuric Japanese adults, including 30 with type 2 diabetes mellitus (T2DM), 104 with metabolic syndrome (MS), and 145 with hypertension (HT).ResultsIn the study population, the urinary albumin:creatinine ratio (UACR) was reduced significantly (ΔUACR −3.8xa0±xa016.8xa0mg/g, Pxa0<xa00.001) with no change in estimated glomerular filtration rate (eGFR) (ΔeGFR −0.4xa0±xa07.4xa0mL/min/1.73xa0m2, Pxa0=xa00.343). The reduction in UACR was associated with decreased fasting plasma glucose (Pxa0<xa00.05). The UACR was also reduced in the T2DM, MS, and HT groups with no change in eGFR. Reduced UACR was associated with decreased fasting plasma glucose in the MS group and decreased systolic blood pressure in the HT group. The UACR was also reduced in 46 subjects using renin–angiotensin system inhibitors with no change in eGFR.ConclusionsOur 12-week lifestyle modification program reduced UACR, maintained eGFR, and improved multiple fitness findings in Japanese subjects including T2DM, MS, and HT patients.

Significant association between renal function and amyloid-positive area in renal biopsy specimens in AL amyloidosis.

BackgroundThe kidney is a major target organ for systemic amyloidosis that often affects the kidney including proteinura, and elevated serum creatinine (Cr). The correlation between amount of amyloid deposits and clinical parameters is not known. The aim of this study was to clarify correlation the amyloid area in all renal biopsy specimen and clinical parameters.MethodsFifty-eight patients with an established diagnosis of AL amyloidosis participated in the study. All patients showed amyloid deposits in renal biopsies. We retrospectively investigated the correlation between clinical data and amyloid occupied area in whole renal biopsy specimens.ResultsThe area occupied by amyloid was less than 10% in 57 of the 58 patients, and was under 2% in 40. For statistical analyses, %amyloid-positive areas were transformed to common logarithmic values (Log10%amyloid). Cr showed significant correlation with Log10%amyloid and estimated glomerular filtration rate (eGFR) showed the significant negative correlation. Patient age, cleatinine clearance (Ccr), blood urea nitorogen, and urinary protein was not significantly correlated with Log10%amyloid. The correlation with other clinical factors such as sex, and serum concentrations of total protein, albumin, immunoglobulins, compliments was evaluated. None of these factors significantly correlated with Log10%amyloid. According to sex- and age- adjusted multiple linear regression analysis, Log10%amyloid had significant positive association with Cr and significant negative association with eGFR.ConclusionThere is significant association between amyloid-positive area in renal tissue and renal function, especially Cr and eGFR. The level of Cr and eGFR may be a marker of amount of amyloid in renal tissue.

High triglyceride is a risk factor for silent osteonecrosis of the femoral head in systemic lupus erythematosus.

The purpose of this study was to clarify the factors related to silent osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE). Seventy-eight patients with SLE were selected on the basis of having been newly diagnosed and requiring high-dose prednisolone, including pulse therapy with methylprednisolone, as the initial treatment. All the patients initially underwent MRI at 3xa0months after the start of corticosteroid treatment to detect any early changes in the femoral head. These examinations were then performed again 3xa0months later. Laboratory parameters were evaluated at the start of steroid treatment and at 1xa0month thereafter. By 3xa0months after the start of corticosteroid treatment, silent ONFH was diagnosed by MRI in 21 patients (26.9xa0%), being bilateral in 11 patients and unilateral in 10. The occurrence of silent ONFH was not related to SLE disease activity index, serological activity, or renal function; it was also unrelated to body mass index (BMI), body surface area (BSA), and the initial dose of prednisolone per unit body weight. However, the total cholesterol level at 4xa0weeks after the start of steroid treatment tended to be higher in patients with silent ONFH. Patients with a higher triglyceride level showed a significantly higher frequency of silent ONFH both before (pu2009=u20090.002) and 4xa0weeks after (pu2009=u20090.036) steroid initiation.A high triglyceride level is an important risk factor for silent ONFH in patients with SLE, and large-scale epidemiologic surveys of such early events are needed in this patient population.

Influence of municipal- and individual-level socioeconomic conditions on mortality in Japan.

BackgroundThe health effect of area socioeconomic conditions has been evident especially in Western countries; however, limited research has focused on the effect of municipal-level socioeconomic conditions, especially in Asia.PurposeMultilevel research using data from the Japan Collaborative Cohort Study, a large cohort study followed from 1990 to 2006, was conducted to examine individual as well as municipal socioeconomic conditions on risk of death, adjusting for each other.MethodWe included 24,460 men and 32,649 women aged 40 to 65xa0years at baseline in 35 municipalities as our study population. Primary predictors were municipal socioeconomic conditions (proportion of college graduates, per capita income, unemployment rate, and proportion of households receiving public assistance) and individual socioeconomic conditions (education level and occupation).ResultsAmong men, the multilevel logistic estimate (standard errors) of proportion of college graduates and unemployment rate for mortality from cardiovascular disease were −0.399 (0.094) and −0.343 (0.122), respectively. Among women, the multilevel logistic estimate (standard errors) of proportion of college graduates and per capita annual income for mortality from injuries were −0.386 (0.171) and −1.069 (0.407). Individual education level and occupation were associated with all-cause mortality, in particular, mortality from cardiovascular disease or injuries. Interactions between individual education level and indicators of municipal socioeconomic conditions were observed for mortality from cancer and cardiovascular disease among men and mortality from injuries among women.ConclusionMunicipal and individual socioeconomic conditions were independently and interactively associated with premature death; this suggests that reducing social inequalities in health demands a focus on municipal conditions in addition to those of individuals.

Real-time polymerase chain reaction analysis of MDM2 and CDK4 expression using total RNA from core-needle biopsies is useful for diagnosing adipocytic tumors

BackgroundDiagnosing adipocytic tumors can be challenging because it is often difficult to morphologically distinguish between benign, intermediate and malignant adipocytic tumors, and other sarcomas that are histologically similar. Recently, a number of tumor-specific chromosome translocations and associated fusion genes have been identified in adipocytic tumors and atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL), which have a supernumerary ring and/or giant chromosome marker with amplified sequences of the MDM2 and CDK4 genes. The purpose of this study was to investigate whether quantitative real-time polymerase chain reaction (PCR) could be used to amplify MDM2 and CDK4 from total RNA samples obtained from core-needle biopsy sections for the diagnosis of ALT/WDL.MethodsA series of lipoma (nu2009=u2009124) and ALT/WDL (nu2009=u200944) cases were analyzed for cytogenetic analysis and lipoma fusion genes, as well as for MDM2 and CDK4 expression by real-time PCR. Moreover, the expression of MDM2 and CDK4 in whole tissue sections was compared with that in core-needle biopsy sections of the same tumor in order to determine whether real-time PCR could be used to distinguish ALT/WDL from lipoma at the preoperative stage.ResultsIn whole tissue sections, the medians for MDM2 and CDK4 expression in ALT/WDL were higher than those in the lipomas (Pu2009<u20090.05). Moreover, karyotype subdivisions with rings and/or giant chromosomes had higher MDM2 and CDK4 expression levels compared to karyotypes with 12q13-15 rearrangements, other abnormal karyotypes, and normal karyotypes (Pu2009<u20090.05). On the other hand, MDM2 and CDK4 expression levels in core-needle biopsy sections were similar to those in whole-tissue sections (MDM2: Pu2009=u20090.6, CDK4: Pu2009=u20090.8, Wilcoxon signed-rank test).ConclusionQuantitative real-time PCR of total RNA can be used to evaluate the MDM2 and CDK4 expression levels in core-needle biopsies and may be useful for distinguishing ALT/WDL from adipocytic tumors. Thus, total RNA from core-needle biopsy sections may have potential as a routine diagnostic tool for other tumors where gene overexpression is a feature of the tumor.