Effects of Xanthine Oxidase Inhibition by Febuxostat on Lipid Profiles of Patients with Hyperuricemia: Insights from Randomized PRIZE Study.

Although patients with hyperuricemia and gout often have dyslipidemia, the effects of febuxostat, a xanthine oxidase inhibitor, on their lipid profiles are unclear. Thus, we performed a sub-analysis of the randomized PRIZE study in which the effects of febuxostat on carotid atherosclerosis were investigated in patients with hyperuricemia. The participants were randomized to the febuxostat or control group. The primary endpoint of this sub-analysis was changes in the patients' non-high-density lipoprotein cholesterol (HDL-C) levels from baseline to 6-month follow-up. Correlations between the changes in lipid profiles and cardiometabolic parameters were also evaluated. In total, 456 patients were included. From baseline to 6 months, non-HDL-C levels were significantly reduced in the febuxostat group (-5.9 mg/dL, 95% confidence interval [CI]: -9.1 to -2.8 mg/dL, p < 0.001), but not in the control group (-1.3 mg/dL, 95% CI: -4.4 to 1.8, p = 0.348). The reduction in non-HDL-C levels was more pronounced in women and correlated with changes in serum uric acid and estimated glomerular filtration rate levels only in the febuxostat group. In patients with hyperuricemia, febuxostat treatment was associated with reduced non-HDL-C levels from baseline to the 6-month follow-up compared to the control treatment, suggesting that the lipid-lowering effect of febuxostat should be considered when targeting dyslipidemia.

Autocrine Regulation of Interleukin-6 via the Activation of STAT3 and Akt in Cardiac Myxoma Cells.

Plasma concentrations of a pleiotropic cytokine, interleukin (IL)-6, are increased in patients with cardiac myxoma. We investigated the regulation of IL-6 in cardiac myxoma. Immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) revealed that IL-6 and its receptors, IL-6 receptor (IL-6R) and gp130, co-existed in the myxoma cells. Myxoma cells were cultured, and an antibody array assay showed that a conditioned medium derived from the cultured myxoma cells contained increased amounts of IL-6. Signal transducer and activator of transcription (STAT) 3 and Akt were constitutively phosphorylated in the myxoma cells. An enzyme-linked immunosorbent assay (ELISA) showed that the myxoma cells spontaneously secreted IL-6 into the culture medium. Real-time PCR revealed that stimulation with IL-6 + soluble IL-6R (sIL6R) significantly increased IL-6 mRNA in the myxoma cells. Pharmacological inhibitors of STAT3 and Akt inhibited the IL-6 + sIL-6R-induced gene expression of IL-6 and the spontaneous secretion of IL-6. In addition, IL-6 + sIL-6R-induced translocation of phosphorylated STAT3 to the nucleus was also blocked by STAT3 inhibitors. This study has demonstrated that IL-6 increases its own production via STAT3 and Akt pathways in cardiac myxoma cells. Autocrine regulation of IL-6 may play an important role in the pathophysiology of patients with cardiac myxoma.

Differentiating Macrovascular and Microvascular Ischemia Using Fractal Analysis of Dynamic Myocardial Perfusion Stress-CT.

OBJECTIVES: Fractal analysis of dynamic myocardial stress computed tomography perfusion imaging (4D-CTP) has shown potential to noninvasively differentiate obstructive coronary artery disease (CAD) and coronary microvascular disease (CMD). This study validates fractal analysis of 4D-CTP in a multicenter setting and assesses its diagnostic accuracy in subgroups with ischemia and nonobstructed coronary arteries (INOCA) and with mild to moderate stenosis. MATERIALS AND METHODS: From the AMPLIFiED multicenter trial, patients with suspected or known chronic myocardial ischemia and an indication for invasive coronary angiography were included. Patients underwent dual-source CT angiography, 4D-CTP, and CT delayed-enhancement imaging. Coronary artery disease, CMD, and normal perfusion were defined by a combined reference standard comprising invasive coronary angiography with fractional flow reserve, and absolute or relative CT-derived myocardial blood flow. Nonobstructed coronary arteries were defined as ≤25% stenosis and mild to moderate stenosis as 26%-80%. RESULTS: In 127 patients (27% female), fractal analysis accurately differentiated CAD (n = 61, 23% female), CMD (n = 23, 30% female), and normal perfusion (n = 34, 35% female) with a multiclass area under the receiver operating characteristic curve (AUC) of 0.92 and high agreement (multiclass κ = 0.89). In patients with ischemia (n = 84), fractal analysis detected CAD (n = 61) over CMD (n = 23) with sensitivity of 95%, specificity of 74%, accuracy of 89%, and AUC of 0.83. In patients with nonobstructed coronary arteries (n = 33), INOCA (n = 15) was detected with sensitivity of 100%, specificity of 78%, accuracy of 88%, and AUC of 0.94. In patients with mild to moderate stenosis (n = 27), fractal analysis detected CAD (n = 19) over CMD with sensitivity of 84%, specificity of 100%, accuracy of 89%, and AUC of 0.95. CONCLUSIONS: In this multicenter study, fractal analysis of 4D-CTP accurately differentiated CAD and CMD including subgroups with INOCA and with mild to moderate stenosis.

Hazards associated with blue light emitted during gas metal arc welding of mild steel using various shielding gases and currents.

Blue light emitted during arc welding is known to potentially cause photoretinopathy. To help prevent retinal injury, it is important to identify the hazards associated with various welding conditions. The present work conducted experiments involving gas metal arc welding of mild steel under various conditions, and measured the spectral radiance of the arcs. The effective radiance values, as used by the American Conference of Governmental Industrial Hygienists (ACGIH) to quantify exposure level of blue light, were subsequently calculated from the data. The resulting values were in the range of 5.0-118 W/cm2/sr, corresponding to hazardous levels according to ACGIH guidelines. The effective radiance was increased at higher welding currents and when pulsed currents were used rather than steady currents. The blue light hazard was also affected by the type of shielding gas employed. These data confirm that it is very hazardous to stare at arcs during gas metal arc welding of mild steel. As such, appropriate eye protection is necessary during arc welding, and directly staring at the arc should be avoided.

Comparison of self-reported symptoms in COVID-19 patients who had or had not previously received COVID-19 mRNA vaccination.

Although mRNA coronavirus disease 2019 (COVID-19) vaccines have been reported for high effectiveness against symptoms, it remains unclear whether post-vaccination infections are less symptomatic than infections in vaccine-naive individuals. We included patients with COVID-19 diagnosed by polymerase chain reaction tests during Japan's alpha and delta variant epidemics. COVID-19 symptoms at approximately 4 weeks were compared based on COVID-19 vaccination status. In total, 398 cases (372 symptomatic and 26 asymptomatic; 286 unvaccinated, 66 vaccinated with one dose, and 46 with two doses) were analyzed. The most common symptoms were fever (78.4%), fatigue (78.4%), cough (74.4%), loss of taste or smell (62.8%), and headache (59.8%). Post-vaccination infections were significantly less likely to be symptomatic. Possible confounder-adjusted odds ratios of two vaccine doses against fatigue, dry eyes and mouth, insomnia, fever, shortness of breath, unusual muscle pains, and loss of taste or smell were 0.18 (95% confidence interval [CI]: 0.09-0.38), 0.22 (95% CI: 0.08-0.59), 0.33 (95% CI: 0.14-0.80), 0.31 (95% CI: 0.15-0.63), 0.36 (95% CI: 0.16-0.76), 0.40 (95% CI: 0.19-0.82), and 0.44 (95% CI: 0.22-0.87), respectively. Post-vaccination infections after two mRNA COVID-19 vaccine doses show milder and fewer symptoms than infections in unvaccinated patients, highlighting the effectiveness of vaccination.

Fractal Analysis of Dynamic Stress CT-Perfusion Imaging for Detection of Hemodynamically Relevant Coronary Artery Disease.

BACKGROUND: Combined computed tomography-derived myocardial blood flow (CTP-MBF) and computed tomography angiography (CTA) has shown good diagnostic performance for detection of coronary artery disease (CAD). However, fractal analysis might provide additional insight into ischemia pathophysiology by characterizing multiscale perfusion patterns and, therefore, may be useful in diagnosing hemodynamically significant CAD. OBJECTIVES: The purpose of this study was to investigate, in a multicenter setting, whether fractal analysis of perfusion improves detection of hemodynamically relevant CAD over myocardial blood flow quantification (CTP-MBF) using dynamic, 4-dimensional, dynamic stress myocardial computed tomography perfusion (CTP) imaging. METHODS: In total, 7 centers participating in the prospective AMPLIFiED (Assessment of Myocardial Perfusion Linked to Infarction and Fibrosis Explored with Dual-source CT) study acquired CTP and CTA data in patients with suspected or known CAD. Hemodynamically relevant CAD was defined as ≥90% stenosis on invasive coronary angiography or fractional flow reserve <0.80. Both fractal analysis and CTP-MBF quantification were performed on CTP images and were combined with CTA results. RESULTS: This study population included 127 participants, among them 61 patients, or 79 vessels, with CAD as per invasive reference standard. Compared with the combination of CTP-MBF and CTA, combined fractal analysis and CTA improved sensitivity on the per-patient level from 84% (95% CI: 72%-92%) to 95% (95% CI: 86%-99%; P = 0.01) and specificity from 70% (95% CI: 57%-82%) to 89% (95% CI: 78%-96%; P = 0.02). The area under the receiver-operating characteristic curve improved from 0.83 (95% CI: 0.75-0.90) to 0.92 (95% CI: 0.86-0.98; P = 0.01). CONCLUSIONS: Fractal analysis constitutes a quantitative and pathophysiologically meaningful approach to myocardial perfusion analysis using dynamic stress CTP, which improved diagnostic performance over CTP-MBF when combined with anatomical information from CTA.

Rapid pretreatment for multi-sample analysis of advanced glycation end products and their role in nephropathy.

Advanced glycation end products (AGEs), produced by the Maillard reaction between carbohydrates and proteins, may be involved in diabetes and its complications. Accurate quantification of AGEs in vivo can demonstrate the relation between AGEs and pathological conditions, but it is not widely used in clinical practice because of the multiple pretreatment steps before analyses. We developed a fully automated solid-phase extraction system (FSPES) to simplify rate-limiting pretreatment using a cation exchange column. We applied this device to evaluate AGEs in nephropathy. Among the standard samples, we used arginine, lysine, N|ε-(carboxymethyl)lysine (CML), N|ω-(carboxymethyl)arginine (CMA), N|ε-(carboxyethyl)lysine (CEL), and N|δ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine (MG-H1) for FSPES. We analyzed the coefficient of variation (CV) by mass spectrometry. FSPES performed column operations rapidly at a pressure three times higher compared with the conventional method. FSPES stably performed pretreatment. CV results for CML, CMA, CEL, and MG-H1 measurements in bovine and human serum were the same as those in the conventional pretreatment. Among the AGE structures we measured, CML and CEL increased with the decline in kidney function. The CML and CEL levels of patients with nephropathy were significantly higher than those in normal subjects. Thus, FSPES is useful for clarifying the relation between AGEs and various pathological conditions.

Real-World Effectiveness of the mRNA COVID-19 Vaccines in Japan: A Case-Control Study.

The real-world effectiveness of the coronavirus disease 2019 (COVID-19) vaccines in Japan remains unclear. This case-control study evaluated the vaccine effectiveness (VE) of two doses of mRNA vaccine, BNT162b2 or mRNA-1273, against the delta (B.1.617.2) variant in the Japanese general population in the period June-September 2021. Individuals in close contact with COVID-19 patients were tested using polymerase chain reaction (PCR). A self-administered questionnaire evaluated vaccination status, demographic data, underlying medical conditions, lifestyle, personal protective health behaviors, and living environment. Two vaccine doses were reported by 11.6% of cases (n = 389) and 35.2% of controls (n = 179). Compared with controls, cases were younger and had a lower proportion who always performed handwashing for ≥20 s, a higher proportion of alcohol consumers, and a lower proportion of individuals living in single-family homes or with commuting family members. After adjusting for these confounding factors and day of PCR testing by multivariate logistic regression analysis, the VE in the period June-July (delta variant proportion 45%) was 92% and 79% in the period August-September (delta variant proportion 89%). The adjusted VE for homestay, hotel-based isolation and quarantine, and hospitalization was 78%, 77%, and 97%, respectively. Despite declining slightly, VE against hospitalization remained robust for ~3 months after the second dose. Vaccination policymaking will require longer-term monitoring of VE against new variants.

Fractal analysis of 4D dynamic myocardial stress-CT perfusion imaging differentiates micro- and macrovascular ischemia in a multi-center proof-of-concept study.

Fractal analysis of dynamic, four-dimensional computed tomography myocardial perfusion (4D-CTP) imaging might have potential for noninvasive differentiation of microvascular ischemia and macrovascular coronary artery disease (CAD) using fractal dimension (FD) as quantitative parameter for perfusion complexity. This multi-center proof-of-concept study included 30 rigorously characterized patients from the AMPLIFiED trial with nonoverlapping and confirmed microvascular ischemia (nmicro = 10), macrovascular CAD (nmacro = 10), or normal myocardial perfusion (nnormal = 10) with invasive coronary angiography and fractional flow reserve (FFR) measurements as reference standard. Perfusion complexity was comparatively high in normal perfusion (FDnormal = 4.49, interquartile range [IQR]:4.46-4.53), moderately reduced in microvascular ischemia (FDmicro = 4.37, IQR:4.36-4.37), and strongly reduced in macrovascular CAD (FDmacro = 4.26, IQR:4.24-4.27), which allowed to differentiate both ischemia types, p < 0.001. Fractal analysis agreed excellently with perfusion state (κ = 0.96, AUC = 0.98), whereas myocardial blood flow (MBF) showed moderate agreement (κ = 0.77, AUC = 0.78). For detecting CAD patients, fractal analysis outperformed MBF estimation with sensitivity and specificity of 100% and 85% versus 100% and 25%, p = 0.02. In conclusion, fractal analysis of 4D-CTP allows to differentiate microvascular from macrovascular ischemia and improves detection of hemodynamically significant CAD in comparison to MBF estimation.

Diagnostic Performance of Dynamic Myocardial Perfusion Imaging Using Dual-Source Computed Tomography.

BACKGROUND: Single-center studies indicated a high diagnostic accuracy of dynamic computed tomography perfusion (CTP) imaging in the diagnosis of coronary artery disease (CAD). OBJECTIVES: This prospective multicenter study determined the diagnostic performance of combined coronary computed tomography angiography (CTA) and CTP for detecting hemodynamically significant CAD defined by invasive coronary angiography (ICA) with fractional flow reserve (FFR). METHODS: Seven centers enrolled 174 patients with suspected or known CAD who were clinically referred for ICA. CTA and dynamic CTP were performed using dual-source CT before ICA. FFR was done as part of ICA in the case of 26% to 90% coronary diameter stenosis. Hemodynamically significant stenosis was defined as FFR of <0.8 or >90% stenosis on ICA. RESULTS: The study protocol was completed in 157 participants, and hemodynamically significant stenosis was detected in 76 of 157 patients (48%) and 112 of 442 vessels (25%). According to receiver-operating characteristic curve analysis, adding dynamic CTP to CTA significantly increased the area under the curve from 0.65 (95% CI: 0.57-0.72) to 0.74 (95% CI: 0.66-0.81; P = 0.011) on the patient level, with decreased sensitivity (93% vs 72%; P < 0.001), improved specificity (36% vs 75%; P < 0.001), and improved overall accuracy (64% vs 74%; P < 0.001). CONCLUSIONS: In this prospective multicenter study on dynamic CTP, the combination of anatomic assessment with coronary CTA and functional evaluation with dynamic CTP allowed more accurate identification of hemodynamically significant CAD compared with CTA alone. However, the clinical significance of this approach needs to be further investigated, including its usefulness in improving prognosis. (Assessment of Myocardial Perfusion Linked to Infarction and Fibrosis Explored With Dual-Source CT [AMPLIFiED]; UMIN000016353).

Prosthetic vascular graft rupture caused by claw-type rib fixation strut: a case report.

A 66-year-old-man who had undergone partial aortic arch and descending aortic graft replacement for a dissecting aortic aneurysm presented to our hospital with pain and beating swelling of his left back shoulder. Enhanced computed tomography and aortic angiography revealed graft rupture caused by one of the claws of a rib fixation strut. Furthermore, another claw had invaded a lung. We performed emergency thoracic endovascular aortic repair, and removed all of the struts 3 weeks later. Claw-type rib fixation struts have the potential to injure other organs, including prosthetic grafts. Careful follow-up is mandatory after implantation of this type of strut.

Eating before bed and new-onset hypertension in a Japanese population: the Iki city epidemiological study of atherosclerosis and chronic kidney disease.

The aim of this study was to determine the relationship between eating before bed and the development of hypertension in a general Japanese population. We conducted a population-based retrospective cohort study using annual health check-up data collected from the residents of Iki City, Nagasaki Prefecture, Japan. In total, 2930 participants without hypertension at baseline (mean age 57.0 years, male 42.8%) were included in the present analysis. Eating before bed was defined as eating within 2 h of bedtime. The outcome of this study was incident hypertension (blood pressure ≥140/90 mmHg or initiation of blood pressure-lowering medications). Multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During an average follow-up of 4.5 years, 909 participants developed hypertension. The incidence (per 1000 person-years) of hypertension in the group of individuals who ate before bed was 82.8, whereas that in the group of individuals who did not eat before bed was 65.8. The association was significant even after adjusting for other risk factors, including age, sex, current smoking status, current alcohol intake, regular exercise, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia, with a hazard ratio of 1.23 (95% CI: 1.05-1.44) for the group of individuals who ate before bed compared with the group of individuals who did not eat before bed (P = 0.01 for trend). Eating before bed was correlated with a future risk of developing hypertension in the general Japanese population.

Effects of Weight Gain after 20 Years of Age and Incidence of Hyper-Low-Density Lipoprotein Cholesterolemia: The Iki Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD).

The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of Japanese people. METHODS: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. RESULTS: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of <10 kg (41.8/1000 person-years). This association remained statistically significant even after adjustment for age, sex, smoking, daily drinking, exercise, obesity, hypertension, and diabetes (multivariable hazard ratio 1.31, 95% confidence interval 1.08-1.58, p = 0.006). CONCLUSION: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese.

Eating Speed and Incidence of Diabetes in a Japanese General Population: ISSA-CKD.

BACKGROUND: We investigated whether eating speed was associated with the incidence of diabetes in a Japanese general population. METHODS: A total of 4853 Japanese individuals without diabetes at baseline were analyzed. Self-reported eating speed was categorized as slow, medium, and fast on the basis of questionnaire responses. The study outcome was the incidence of diabetes. RESULTS: After an average follow-up period of 5.1 years, 234 individuals developed diabetes. The incidence of diabetes per 1000 person-years was 4.9 in the slow eating speed group, 8.8 in the medium eating speed group, and 12.5 in the fast eating speed group, respectively (*** p < 0.001 for trend). The HRs were 1.69 (95%CI 0.94-3.06) for the medium eating speed and 2.08 (95%CI 1.13-3.84) for the fast eating speed, compared to the slow eating speed (* p = 0.014 for trend) after adjustment for age, gender, smoking status, drinking, exercise, obesity, hypertension, and dyslipidemia. CONCLUSION: Faster eating speed increased a risk for the incidence of diabetes in a general Japanese population.

Association between serum uric acid and new onset and progression of chronic kidney disease in a Japanese general population: Iki epidemiological study of atherosclerosis and chronic kidney disease.

BACKGROUND: Although several risk factors for chronic kidney disease (CKD) have been proposed, it remains unclear whether elevated serum uric acid (SUA) is negatively association with kidney function. The aim of this study was to elucidate the association between SUA and new onset and progression of CKD in a Japanese general population. METHODS: This was a population-based retrospective cohort study using annual health checkup data of residents of Iki Island. A total of 5,507 adults (979 with CKD and 4,528 without) were included. The outcomes were new onset of CKD among participants without CKD at baseline, and progression of CKD among those with CKD. A Cox proportional hazards model was used to evaluate the association between SUA and new onset and progression of CKD. RESULTS: During mean follow-up of 4.6 years, 757 cases of new onset of CKD and 193 with progression of CKD were observed. SUA was significantly associated with new onset of CKD (adjusted hazard ratio 1.13, [95% confidence interval 1.03-1.24] per standard deviation [SD] increase in SUA). In contrast, SUA was not significantly associated with progression of CKD (hazard ratio 1.08, [0.92-1.27] per SD increase). Similar results were obtained when classifying uric acid as categorical. CONCLUSION: SUA was significantly associated with increased risk for new onset of CKD, but not with progression of CKD among a Japanese general population.

Genetic testing and serological screening for SARS-CoV-2 infection in a COVID-19 outbreak in a nursing facility in Japan.

BACKGROUND: The Pandemic of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has critically impacted the spread of infection within nursing facilities. We evaluated the usefulness of genetic and serological tests conducted during a COVID-19 outbreak in a nursing facility in Japan. METHODS: After the first identification of SARS-CoV-2 infection, a comprehensive, facility- and/or unit-wide PCR testing from nasopharyngeal swabs was repeatedly performed in a three-unit facility including 99 residents with dementia and 53 healthcare personnel. Additionally, PCR testing was conducted separately for residents and staff with fever of ≥37.5 °C. Facility-wide serological testing, including rapid kit testing and quantitative assay, was conducted twice over 1 month apart. RESULTS: A total of 322 PCR and 257 antibody tests were performed. 37 (24.3%) of the 152 individuals (25/99 residents, 25.3%; 12/53 staff, 22.6%) were identified as PCR-positive. Seven residents died with a mortality of 7.1% (7/99). Among the 37 individuals, 10 (27.0%) were asymptomatic at the time of testing. PCR positivity was concentrated on one unit (Unit 1) (20/30 residents, 66.7%; 9/14 staff, 64.3%). The other units showed a limited spread of infection. In unit-wide and separate tests, PCR positivity detection was highly prevalent (22.9 and 44.4%, respectively) in Unit 1, compared with that in the other units. Serological testing identified two additional infected residents with a negative PCR result and showed that no staff was newly identified as infected. CONCLUSIONS: Thorough PCR testing, in combination with comprehensive and separate tests, is critical for managing COVID-19 outbreaks in nursing facilities, particularly, in units considered an epicenter. Serological testing is also beneficial for tracing contacts, confirming the number of infected individuals, and authorizing the termination of the outbreak.

White blood cell count and incidence of hypertension in the general Japanese population: ISSA-CKD study.

OBJECTIVES: This study aimed to clarify the relationship between the white blood cell (WBC) count and hypertension in the general Japanese population. METHODS: We conducted a population-based retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. A total of 2935 participants without hypertension at baseline were included in the present analysis. WBC counts were classified as tertile 1 (<4700/µL), tertile 2 (4700-5999/µL), and tertile 3 (≥6000/µL). The outcome was incident hypertension (blood pressure ≥140 mmHg). Multivariable-adjusted hazard ratios and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazards model. RESULT: During an average follow-up of 4.5 years, 908 participants developed hypertension. The incidence (per 100 person-years) of hypertension increased with an elevation in the WBC count (6.3 in tertile 1, 7.0 in tertile 2, and 7.4 in tertile 3). This association was significant, even after adjustment for other risk factors, including age, sex, current smoking habits, current alcohol intake, exercise habits, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia. The hazard ratios were 1.07 for tertile 2 (95% CI 0.90-1.26) and 1.27 for tertile 3 (95% CI 1.06-1.51) compared with the reference group of tertile 1 (p = 0.009). CONCLUSION: The WBC count was associated with future development of hypertension in the general Japanese population.