Refractory Oral Ulcer Responsive to Infliximab: A Case Report.

PURPOSE: Some oral ulcers are refractory to treatment. Recently, anti-tumor necrosis factor-alpha (anti-TNF-α) agents have been shown to induce relatively long remissions of refractory oral ulcers. METHODS: A 69-year man presented with a sore throat caused by a pharyngeal ulcer in the soft palate and subsequently repeatedly developed oropharyngolaryngeal ulcers and an ulcer in the ileocecal region. Intestinal Behçet disease was suspected, but he did not meet the diagnostic criteria for this condition. Seven months after the initial presentation, he developed a lingual ulcer that did not resolve despite treatment with prednisolone. Given the suspicion of intestinal Behçet disease, 300 mg of infliximab was administered intravenously. RESULTS: After the third dose of infliximab with prednisolone, the ulcer began to improve. He received infliximab every 8 weeks thereafter and developed no new oropharyngolaryngeal ulcers during the 17 months after the first infusion of infliximab. CONCLUSIONS: When a patient has refractory oral ulcers, attention must be paid to digestive symptoms and whether the patient has a systemic disease such as Behçet disease investigated. Furthermore, administration of infliximab to patients with refractory ulcers can be considered even when they do not fulfill the clinical criteria for a systemic disease.

Combination of Helicobacter pylori Antibody and Serum Pepsinogen as a Good Predictive Tool of Gastric Cancer Incidence: 20-Year Prospective Data From the Hisayama Study.

BACKGROUND: There is little information regarding whether the combination of Helicobacter pylori (H. pylori) antibody and serum pepsinogen (sPG), which is a marker of the degree of atrophic gastritis, has a discriminatory ability for detecting incident gastric cancer. We examined this issue in a long-term prospective cohort study of a Japanese population. METHODS: A total of 2446 Japanese community-dwelling individuals aged ≥40 years were stratified into four groups according to baseline H. pylori serological status and sPG: Group A (H. pylori[-], sPG[-]), Group B (H. pylori[+], sPG[-]), Group C (H. pylori[+], sPG[+]), and Group D (H. pylori[-], sPG[+]), and participants were followed up prospectively for 20 years. RESULTS: During the follow-up, 123 subjects developed gastric cancer. Compared with that in Group A, the cumulative incidence of gastric cancer was significantly increased in Groups B, C, and D, whereas no significant difference was found between Groups C and D. The multivariable-adjusted risk of gastric cancer was significantly increased in Group B (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.62-10.28) and in Groups C and D combined (HR 11.1; 95% CI, 4.45-27.46). When the multivariable model with H. pylori antibody was changed into that with the combination of H. pylori antibody and sPG, the C statistics for developing gastric cancer increased significantly (0.773 vs 0.732, P = 0.005), and the continuous net reclassification improvement value was 0.591 (P < 0.001). CONCLUSIONS: Our findings suggest that the combination of H. pylori antibody and sPG is a useful tool for predicting the development of gastric cancer.

Secular trends in cardiovascular disease and its risk factors in Japanese: half-century data from the Hisayama Study (1961-2009).

BACKGROUND: Changes in lifestyle and advances in medical technology during the past half century are likely to have affected the incidence and mortality of cardiovascular disease and the prevalence of its risk factors in Japan. METHODS AND RESULTS: We established 5 cohorts consisting of residents aged ≥40 years in a Japanese community, in 1961 (n=1618), 1974 (n=2038), 1983 (n=2459), 1993 (n=1983), and 2002 (n=3108), and followed up each cohort for 7 years. The age-adjusted incidence of stroke decreased greatly, by 51% in men and by 43% in women, from the 1960s to the 1970s, but this decreasing trend slowed from the 1970s to the 2000s. Among the stroke subtypes, ischemic stroke in both sexes and intracerebral hemorrhage in men showed a similar pattern. Stroke mortality decreased as a result of the decline in incidence and a significant improvement in survival rate. Although the incidence of acute myocardial infarction did not change in either sex, disease mortality declined slightly in women. From the 1960s to the 2000s, blood pressure control among hypertensive individuals improved significantly and the smoking rate decreased, but the prevalence of glucose intolerance, hypercholesterolemia, and obesity increased steeply. CONCLUSIONS: Our findings suggest that in Japanese, the decreasing trends in the incidence of ischemic stroke have recently slowed down, and there has been no clear change in the incidence of acute myocardial infarction, probably because the benefits of hypertension control and smoking cessation have been negated by increasing metabolic risk factors.

Trends in the incidence and survival of intracerebral hemorrhage by its location in a Japanese community.

BACKGROUND: No previous population-based studies have examined secular trends in the incidence of intracerebral hemorrhage (ICH) by its location. METHODS AND RESULTS: We established 3 cohorts consisting of residents of Hisayama, Japan, aged ≥40 years without a history of stroke or myocardial infarction in 1961 (the first cohort, n=1,618), in 1974 (the second cohort, n=2,038), and in 1988 (the third cohort, n=2,637). Each cohort was followed for 13 years. The age- and sex-adjusted incidence of ICH significantly declined from the first to the second cohort and showed no further change in the third cohort. With regard to the ICH location, the incidence of putaminal hemorrhage decreased steadily, mainly in subjects aged 60-69 years, whereas the incidence of thalamic hemorrhage increased, especially in those aged ≥70 years. Both hypertension and alcohol intake were strong risk factors for ICH in the first cohort, but their influence declined with time. Blood pressure levels in hypertensive subjects decreased significantly, and the proportion of current drinkers decreased slightly over the study period. CONCLUSIONS: Our findings suggest that the ICH incidence steeply declined from the 1960s to the 1970s in Japan as a result of the reduced influence of hypertension and alcohol intake, but that this decline has leveled off since then, probably because of the increased incidence of thalamic hemorrhage in the elderly in recent years.

Diabetes mellitus and cancer risk: review of the epidemiological evidence.

Diabetes mellitus and cancer are diseases of epidemic proportions across the globe. These diseases are influenced by many factors, both genetic and environmental. A possible association between diabetes and cancer risk has long been speculated. Increased incidence of several cancers has been observed in diabetes patients, notably pancreatic, hepatic, colorectal, breast, urinary tract, and endometrial cancers. In contrast, a decreased incidence of prostate cancer is observed in diabetes patients, implying a protective effect. Precise knowledge of the complex associations and interactions between these two conditions is of great importance for their prevention and treatment. Multiple potential mechanisms have been proposed, but they have tended to be site-specific. Possible common mechanisms for a biological link between diabetes and cancer include hyperinsulinemia, hyperglycemia, and inflammation. Today, 366 million people live with diabetes globally, and this figure is expected to increase. Thus, if diabetes is associated with even a small increase in cancer risk, this may have important consequences at the population level. The aim of this review is to summarize recent epidemiological evidence of an association between diabetes and total cancer and specific sites of cancer, and to consider causal associations between these diseases.

Haemoglobin A1c even within non-diabetic level is a predictor of cardiovascular disease in a general Japanese population: the Hisayama Study.

BACKGROUND: There is little information about predictive ability of haemoglobin A1c (HbA1c) for cardiovascular disease (CVD) in Asians. To investigate the discriminatory ability of HbA1c to identify subjects who are at greater risk of developing CVD in a prospective study of a defined community-dwelling Japanese population. METHODS: A total of 2,851 subjects aged 40-79 years were stratified into five groups (HbA1c levels with ≤ 5.0, 5.1-5.4, 5.5-6.4, and ≥ 6.5% and a group with antidiabetic medication) and followed up prospectively for 7 years (2002-2009). RESULTS: During the follow-up, 119 subjects developed CVD. The multivariable-adjusted risk of CVD was significantly increased in subjects with HbA1c levels of 5.5-6.4 and ≥ 6.5% and diabetic medication compared to HbA1c level with ≤ 5.0% (hazard ratio, 2.26 [95% confidence interval, 1.29-3.95] for the 5.5-6.4%; 4.43 [2.09-9.37] for the ≥ 6.5%; and 5.15 [2.65-10.0] for the antidiabetic medication group). With regard to CVD subtype, the positive associations between HbA1c levels and the risk of coronary heart disease (CHD) and ischaemic stroke were also significant, but no such associations were seen for haemorrhagic stroke. The C statistic for developing CVD was significantly increased by adding HbA1c values to the model including other risk factors (0.789 vs. 0762, p = 0.006), and the net reclassification improvement was 0.105 (p = 0.004). CONCLUSIONS: Our findings suggest that elevated HbA1c levels are an independent risk factor for CVD, especially CHD and ischaemic stroke, and that the addition of HbA1c to the model with traditional risk factors significantly improves the predictive ability of CVD.

Optimal cutoff value of the serum pepsinogen level for prediction of gastric cancer incidence: the Hisayama Study.

BACKGROUND: Serum pepsinogen (sPG) levels have been established as a good marker of chronic atrophic gastritis and the sequential occurrence of gastric cancer. However, there have been few prospective investigations which investigated the predictive performance of sPG for future gastric cancer incidence. SUBJECTS AND METHODS: We prospectively followed-up a total of 2446 community-dwelling Japanese aged ≥ 40 years for 10 years and used the Youden's index to determine the cutoff values of the pepsinogen I level and pepsinogen I/II ratio to accurately discriminate gastric cancer events. Predictive performance of sPG was assessed by ROC curve. RESULTS: During the follow-up, 69 subjects developed gastric cancer. The most predictive sPG test criteria were determined to be a pepsinogen I level ≤ 59 ng/ml and pepsinogen I/II ratio ≤ 3.9. The sensitivity and specificity of these criteria to discriminate the actual occurrence of gastric cancer were 71.0% and 69.2%, respectively. The area under the ROC curve for gastric cancer occurrence increased significantly by adding the sPG test to the model that included the status of Helicobater pylori infection and other potential risk factors (from 0.742 to 0.809; p for difference in the area < 0.001). CONCLUSIONS: This study determined the optimal sPG test criteria for predicting gastric cancer occurrence over 10 years in a general Japanese population. These criteria would be effective to screen for individuals at high risk of this disease.

Colorectal cancer screening with odour material by canine scent detection.

OBJECTIVE: Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. DESIGN: Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. RESULTS: 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. CONCLUSIONS: This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.

Hyperglycemia increases risk of gastric cancer posed by Helicobacter pylori infection: a population-based cohort study.

BACKGROUND & AIMS: Although diabetes mellitus and hyperglycemia are considered to be possible risk factors for various types of malignancy, the epidemiologic evidence concerning gastric cancer is scarce. The aim of this study was to evaluate the impact of hemoglobin A1c (HbA1c) levels on gastric cancer occurrence and their interaction with Helicobacter pylori infection. METHODS: A total of 2603 Japanese subjects aged>or=40 years were stratified into 4 groups according to baseline HbA1c levels (or=7.0%) and followed up prospectively for 14 years. RESULTS: During the follow-up, 97 subjects developed gastric cancer. The age- and sex-adjusted incidence of gastric cancer significantly increased in the 6.0%-6.9% (5.1 per 1000 person-years; P<.05) and >or=7.0% groups (5.5 per 1000 person-years; P<.05) compared with the 5.0%-5.9% group (2.5 per 1000 person-years), whereas it was slightly but not significantly high in the or=7.0% group). Among subjects who had both high HbA1c levels (>or=6.0%) and Helicobacter pylori infection, the risk of gastric cancer was dramatically elevated (interaction term, P=.004). CONCLUSIONS: Our findings suggest that casual hyperglycemia is a risk factor for gastric cancer and is a possible cofactor increasing the risk posed by Helicobacter pylori infection.

Population-based prospective study of the combined influence of cigarette smoking and Helicobacter pylori infection on gastric cancer incidence: the Hisayama Study.

The authors assessed the separate and joint influences of cigarette smoking and Helicobacter pylori infection on the development of gastric cancer in a population-based prospective study. A total of 1,071 Japanese men aged > or =40 years were followed up prospectively for 14 years (1998-2002). Compared with that for current nonsmokers, the multivariate-adjusted hazard ratios of gastric cancer for smokers of 1-9, 10-19, and > or =20 cigarettes per day were 1.36 (95% confidence interval (CI): 0.50, 3.71), 1.93 (95% CI: 1.01, 3.67), and 1.88 (95% CI: 1.02, 3.43), respectively. The risk of gastric cancer increased steeply for subjects who had both a smoking habit and H. pylori infection compared with those who did not have both risk factors (hazard ratio = 11.41, 95% CI: 1.54, 84.67). If causal, the estimated population attributable fraction of gastric cancer for cigarette smoking was approximately half that for H. pylori infection (28.4% vs. 56.2%). The overlap of the population attributable fractions for the 2 factors was 49.6%. Findings suggest that cigarette smoking and H. pylori infection are significant risk factors for gastric cancer in Japanese men, and the magnitude of their combined influence is considerable.

Association of serum lipocalin-type prostaglandin D synthase levels with subclinical atherosclerosis in untreated asymptomatic subjects.

Recent studies suggest that lipocalin-type prostaglandin (PG) D synthase (L-PGDS), which converts PGH2 to PGD2, is implicated in the pathogenesis of atherosclerosis. However, clinical evidence for the association between serum L-PGDS levels and atherosclerosis has not been reported. In this study, we measured the serum L-PGDS concentration using sandwich enzyme-linked immunosorbent assay (ELISA) and investigated the association with traditional cardiovascular risk factors and surrogate atherosclerotic indices, such as the maximum score of the intima-media complex thickness of the carotid artery (C-IMT(max)) and the brachial-ankle pulse wave velocity (ba-PWV), in 500 non-treated asymptomatic subjects. The serum concentration of L-PGDS was 0.56+/-0.01 (mean+/-SEM, range 0.25-1.27, median 0.54) mg/L. Serum L-PGDS levels increased with age and were higher in men than in women. Serum L-PGDS was higher in subjects with hypertension and increased with increasing numbers of the traditional atherosclerotic risk factors. When the subjects were divided into four groups according to the levels of serum L-PGDS, the age-adjusted values of C-IMT(max) and ba-PWV were significantly increased in subjects with higher serum L-PGDS levels (quartile 3 and quartile 4) compared to those in the lowest quartile (quartile 1), for both genders. Multiple regression analysis including risk factors revealed that serum L-PGDS was an independent determinant for ba-PWV (beta=0.130, p<0.001). Serum L-PGDS tended to associate with C-IMT(max) but was not statistically significant (beta=0.084, p=0.075). In conclusion, our results suggest that an increase in serum L-PGDS concentration is associated with the progression of atherosclerosis.

C-reactive protein and risk of first-ever ischemic and hemorrhagic stroke in a general Japanese population: the Hisayama Study.

BACKGROUND AND PURPOSE: The role of high-sensitivity C-reactive protein (hsCRP) in the development of stroke is not clearly understood. We investigated the relationship between serum hsCRP levels and stroke occurrence in a general Japanese population. METHODS: We followed 2692 subjects > or =40 years of age for 12 years. The relative risks and 95% CIs for ischemic and hemorrhagic stroke occurrence were calculated according to the hsCRP quintiles. RESULTS: During the follow-up, 129 first-ever ischemic and 59 hemorrhagic strokes occurred. In men, the age-adjusted incidence of ischemic stroke significantly increased with elevated serum hsCRP levels; the difference between the first and fifth quintiles was statistically significant (1.4 versus 6.6 per 1000 person-years; P=0.02). This association remained significant even after adjustment for other confounding factors, such as age, systolic blood pressure, ECG abnormalities, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol, smoking habits, alcohol intake, and regular exercise (adjusted relative risks, 3.11; 95% CI, 1.04 to 9.32; P=0.04). However, such associations were not observed for ischemic stroke in women or in hemorrhagic stroke in either sex. Among male subjects who were both in the fifth hsCRP level and had hypertension, diabetes, obesity, hypercholesterolemia, or a smoking habit, the risk of ischemic stroke was extremely increased, even after adjustment for other risk factors. CONCLUSIONS: Our findings suggest that elevated serum hsCRP levels are an independent risk factor for future ischemic stroke in Japanese men and that the coexistence of a high hsCRP level with another risk factor extremely increases the risk of ischemic stroke.

Small bowel injury induced by selective cyclooxygenase-2 inhibitors: a prospective, double-blind, randomized clinical trial comparing celecoxib and meloxicam.

BACKGROUND: Selective cyclooxygenase (COX)-2 inhibitors are less harmful to the small bowel mucosa than non-selective anti-inflammatory drugs. We aimed to compare the severity of small bowel mucosal injury in healthy volunteers induced by two selective COX-2 inhibitors, celecoxib and meloxicam, in a randomized, double-blind trial, using capsule endoscopy (CE). METHODS: Twenty-nine healthy subjects were randomized to take either celecoxib (200 mg twice daily) or meloxicam (10 mg once daily) for 2 weeks. The incidence and the number of small bowel mucosal injuries (bleeding, ulcers, and erosions) observed by CE were compared between the two groups. RESULTS: The overall incidence of small bowel mucosal injury was not different between the celecoxib group (6 of 14 subjects, 42.9%) and the meloxicam group (4 of 15 subjects, 26.7%, P = 0.45). In subjects with positive CE findings, the number of ulcers was greater in the meloxicam group than in the celecoxib group (P = 0.02), while such a trend was not found with regard to erosions (P = 0.52). The distribution of mucosal lesions within the small bowel was similar in the two groups. CONCLUSIONS: Selective COX-2 inhibitors are not completely safe for the small bowel. The mucosal lesions may be less severe with celecoxib than with meloxicam.

Liver enzymes as a predictor for incident diabetes in a Japanese population: the Hisayama study.

OBJECTIVE: We studied the relationship between liver enzymes and the development of diabetes in a general Japanese population. RESEARCH METHODS AND PROCEDURES: A total of 1804 non-diabetic subjects 40 to 79 years of age were followed-up prospectively for a mean of 9.0 years. RESULTS: During the follow-up, 135 subjects developed diabetes. In both sexes, the age-adjusted cumulative incidence of diabetes increased significantly with elevating quartiles of serum gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) levels. This pattern was also observed in aspartate aminotransferase (AST) quartiles for men but not for women. In multivariate analyses after adjusting for comprehensive risk factors and other liver enzymes, the risk of developing diabetes was significantly higher in the highest GGT quartile than in the lowest quartile [odds ratio (OR), 2.54; 95% confidence interval (CI), 1.03 to 6.26 for men; OR, 5.73; 95% CI, 1.62 to 20.19 for women]. Similar results were observed in ALT quartiles (OR, 2.32; 95% CI, 0.91 to 5.92 for men; OR, 4.40; 95% CI, 1.38 to 14.06 for women) but not in AST quartiles in either sex. Significant positive associations of GGT and ALT with diabetes were seen within each stratified category of risk factors, namely fasting insulin, BMI, waist-to-hip ratio, high-sensitivity C-reactive protein, and alcohol consumption. In receiver operating characteristic analyses, the areas under the receiver operating characteristic curve of GGT and ALT were significantly larger than that of AST, fasting insulin, waist-to-hip ratio, or C-reactive protein. DISCUSSION: Our findings suggest that serum GGT and ALT concentrations are strong predictors of diabetes in the general population, independent of known risk factors.

The serum pepsinogen test as a predictor of gastric cancer: the Hisayama study.

The authors examined whether a serum pepsinogen test (SPT) based on the combination of the serum pepsinogen I level and pepsinogen I/II ratio is a good predictor of gastric cancer occurrence in a general Japanese population. A total of 2,446 subjects aged > or =40 years were classified into negative, positive, and strong-positive SPT groups and were followed prospectively for 14 years (1988-2002). Compared with that for the negative SPT group (26 men, 10 women), gastric cancer incidence increased significantly for both men (n = 17; age-adjusted hazard ratio = 4.56, 95% confidence interval: 2.42, 8.60) and women (n = 6; age-adjusted hazard ratio = 5.84, 95% confidence interval: 2.00, 17.11) in the strong-positive SPT group. It was also significantly higher in the positive SPT group for men (n = 23; age-adjusted hazard ratio = 3.91, 95% confidence interval: 2.23, 6.86). These associations did not attenuate even after adjustment for other comprehensive risk factors. Stratified analysis revealed significant associations between the SPT and development of intestinal-type gastric cancer as well as of cancer in both Helicobacter pylori-negative and -positive subjects. These findings suggest that the SPT can serve as a predictor of intestinal-type gastric cancer, irrespective of H. pylori infection.

A prospective study of dietary salt intake and gastric cancer incidence in a defined Japanese population: the Hisayama study.

The results of prospective studies of the association between dietary salt intake and gastric cancer occurrence remain controversial. To examine this issue in a cohort study of a general population, 2,476 subjects aged 40 years or older were stratified into 4 groups according to the amount of daily salt intake: namely, <10.0, 10.0-12.9, 13.0-15.9, and > or = 16.0 per day and were followed up prospectively for 14 years. During the follow-up period, 93 subjects developed gastric cancer. The age- and sex-adjusted incidence was significantly higher in the second to fourth groups than in the first group (age- and sex-adjusted hazard ratio [95% confidence interval], 2.42 [1.24-4.71] for the second group; 2.10 [1.03-4.30] for the third group; 2.98 [1.53-5.82] for the fourth group). This association remained substantially unchanged even after adjusting for other confounding factors such as age, sex, Helicobacter pylori infection, atrophic gastritis, medical history of peptic ulcer, family history of cancer, body mass index, diabetes, total cholesterol, physical activity, alcohol intake, smoking habit and other dietary factors. In the stratified analysis, a significant salt-cancer association was observed only in subjects who had both Helicobacter pylori infection and atrophic gastritis (age- and sex-adjusted hazard ratio, 2.87 [1.14-7.24]). Our findings suggest that high dietary salt intake is a significant risk factor for gastric cancer; moreover, this association was found to be strong in the presence of Helicobacter pylori infection with atrophic gastritis.

Gastric juvenile polyposis associated with germline SMAD4 mutation.

We treated a 39-year-old woman with hypoproteinemia and anemia who had profuse gastric polyposis. Radiographic and endoscopic examination showed numerous polyps restricted to the stomach. The patient had pulmonary arteriovenous malformations in the left lung. Histological examination of the resected stomach revealed the gastric polyposis to be composed of cystic dilatation of the glands with small areas of adenocarcinoma. These findings were compatible with gastric juvenile polyposis (GJP) accompanied by gastric cancer. Analysis of genomic DNA revealed that the patient had truncating mutation of SMAD4, a responsible gene for juvenile polyposis (JP). Our case suggests that SMAD4 is possibly a responsible gene for GJP.

Secular trends in the incidence, mortality, and survival rate of gastric cancer in a general Japanese population: the Hisayama study.

To examine secular trends in the incidence and mortality of gastric cancer in a Japanese community, Hisayama, we established three study-cohorts of Hisayama residents aged > or =40 years in 1961 (1637 subjects), 1974 (2054), and 1988 (2602). Each cohort was followed up for ten years. The age-standardized mortality from gastric cancer significantly decreased from 2.4 per 1000 person-years in the first cohort to 0.8 in the third cohort for men, and from 1.0 to 0.2, respectively, for women (p < 0.01 for trend in both sexes). The five-year survival rate after gastric cancer significantly improved from the first (32.6%) to the third cohort (73.0%, p < 0.01) for men and from 43.2% to 72.3% (p < 0.05), respectively, for women. The age-standardized incidence of cancer in men was not different among the cohorts (4.3 per 1000 person-years in the first, 5.0 in the second, and 4.9 in the third cohort), while it decreased significantly in women (2.0, 1.8, and 1.2, respectively, p < 0.01 for trend). In conclusion, our findings suggest that in a Japanese population, the mortality from gastric cancer declined during the past 40 years, due mainly to the improvement of survival in both sexes and a decrease in the incidence for women.

Chronic kidney disease and cardiovascular disease in a general Japanese population: the Hisayama Study.

BACKGROUND: Chronic kidney disease has been shown to be an independent risk factor for cardiovascular disease in high-risk populations. However, this relationship is inconclusive in community-based populations. METHODS: To clarify this issue, we followed 2634 community-dwelling individuals without cardiovascular disease, aged 40 years or older, for 12 years and examined the relationship between chronic kidney disease and the incidence of cardiovascular disease. RESULTS: During the follow-up period, 99 subjects (56 men and 43 women) experienced coronary heart disease, 137 subjects (60 men and 77 women) ischemic stroke, and 60 subjects (26 men and 34 women) hemorrhagic stroke. In men, the age-adjusted incidence of coronary heart disease was significantly higher in subjects with chronic kidney disease than in those without it (6.2 vs. 2.9 per 1000 person-years) (P < 0.05), but such a relationship was not observed with ischemic stroke. In contrast, in women, the age-adjusted incidence of ischemic stroke was significantly higher in subjects with chronic kidney disease than in those without it (3.4 vs. 2.5) (P < 0.05), while that of coronary heart disease was not. Chronic kidney disease was not found to be associated with the incidence of hemorrhagic stroke. In multivariate analysis, even after adjustments for traditional and nontraditional cardiovascular disease risk factors, chronic kidney disease was found to be an independent risk factor for the occurrence of coronary heart disease in men [hazard ratio (HR), 2.26; 95% CI, 1.06-4.79], and for the occurrence of ischemic stroke in women (HR, 1.91; 95% CI, 1.15-3.15). CONCLUSION: Our findings suggest that chronic kidney disease is an independent risk factor for the occurrence of cardiovascular disease in the general Japanese population.