論文

Background: Heated tobacco products (HTPs) have gained global popularity, but their health risks remain unclear. Therefore, the current study aimed to identify plasma metabolites associated with smoking and HTP use in a large Japanese population to improve health risk assessment.Methods: Metabolomics data from 9,922 baseline participants of the Tsuruoka Metabolomics Cohort Study (TMCS) were analyzed to determine the association between smoking habits and plasma metabolites. Moreover, alterations in smoking-related metabolites among HTP users were examined based on data obtained from 3,334 participants involved from April 2018 to June 2019 in a follow-up survey.Results: Our study revealed that cigarette smokers had metabolomics profiles distinct from never smokers, with 22 polar metabolites identified as candidate biomarkers for smoking. These biomarker profiles of HTP users were closer to those of cigarette smokers than those of never smokers. The concentration of glutamate was higher in cigarette smokers, and biomarkers involved in glutamate metabolism were also associated with cigarette smoking and HTP use. Network pathway analysis showed that smoking was associated with the glutamate pathway, which could lead to endothelial dysfunction and atherosclerosis of the vessels.Conclusion: Our study showed that the glutamate pathway is affected by habitual smoking. These changes in the glutamate pathway may partly explain the mechanism by which cigarette smoking causes cardiovascular disease. HTP use was also associated with glutamate metabolism, indicating that HTP use may contribute to the development of cardiovascular disease through mechanisms similar to those in cigarette use.

Background: Prevention of heart failure (HF) is a public health issue. Using the National Vital Statistics, we explored risk factors for HF and coronary artery disease (CAD) mortality.Methods and Results: Altogether, 7,556 Japanese individuals aged ≥30 years in 1990 were followed over 25 years; of these, 139 and 154 died from HF and CAD, respectively. In multivariable Cox proportional hazard analysis, common risk factors for CAD and HF mortality were hypertension (hazard ratio [HR] 1.48 [95% confidence interval {CI} 1.00–2.20] and 2.31 [95% CI 1.48–3.61], respectively), diabetes (HR 2.52 [95% CI 1.63–3.90] and 2.07 [95% CI 1.23–3.50], respectively), and current smoking (HR 2.05 [95% CI 1.27–3.31) and 1.86 [95% CI 1.10–3.15], respectively). Specific risk factors for CAD were male sex, chronic kidney disease, history of cardiovascular disease, and both abnormal T and Q waves, with HRs (95% CIs) of 1.75 (1.05–2.92), 1.78 (1.19–2.66), 2.50 (1.62–3.88), and 11.4 (3.64–36.0), respectively. Specific factors for HF were current drinking (HR 0.43; 95% CI 0.24–0.78) and non-high-density lipoprotein cholesterol (non-HDL-C; HR 0.81; 95% CI 0.67–0.98). There was an inverse association between non-HDL-C and HF in those aged ≥65 years (HR 0.71; 95% CI 0.56–0.90), but not in those aged <65 years.Conclusions: We identified common risk factors for HF and CAD deaths; a history of cardiovascular disease was a specific risk for CAD.

Although metabolic syndrome, including visceral fat accumulation, causes kidney and cardiovascular diseases, the impact of visceral fat accumulation on mild decreased renal function remains unclear. This study examines the association between visceral fat area (VFA) measured by bioimpedance methods and the estimated glomerular filtration rate based on serum cystatin C (eGFRcys) in the Japanese urban population. This community-based cross-sectional study enrolled 952 individuals (287 men, 665 women) who participated in the second follow-up survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. We compared the multivariate-adjusted means of eGFRcys among VFA quartile groups by gender using the analysis of covariance. Models were adjusted for age, high blood pressure, hypercholesterolemia, glucose intolerance, smoking, and alcohol use, and further adjusted for body mass index (BMI). The highest VFA quartile group had lower eGFRcys than the lowest VFA quartile group after adjusted for cardiometabolic risk factors, except for BMI (93.1 [95% confidence interval (CI), 90.1–96.2] vs. 82.1 [95% CI, 79.1–85.0] in men and 95.8 [95% CI, 94.1–97.5] vs. 89.4 [95% CI, 87.8–90.9] in women). Moreover, further adjustment for BMI revealed a similar result in men (93.5 [95% CI, 89.8–97.2] vs. 81.6 [95% CI, 77.9–85.3]), while no significant association was found in women. This study suggests a significant association between increased VFA levels and lower eGFRcys levels independent of cardiometabolic risk factors, such as glucose intolerance and hypercholesterolemia in men and women, as well as independent of BMI in men.

Objective To consider effective measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in medical institutions, this study estimated the SARS-CoV-2 infection rate among healthcare workers (HCWs) in Tokyo, Japan, and determined the specific findings for mild coronavirus disease 2019 (COVID-19) cases. Methods This study analyzed the results of serologic tests to detect immunoglobulin G antibodies against SARS-CoV-2 and evaluated the demographic and clinical characteristics of the faculty and HCWs at a Tokyo medical institution in August 2020. The demographic and clinical characteristics of participants with antibody-positive results were compared to those of participants with antibody-negative results. Materials This study recruited 2,341 faculty and HCWs at a Tokyo medical institution, 21 of whom had a COVID-19 history. Results Of the 2,320 participants without a COVID-19 history, 20 (0.862%) had positive serologic test results. A fever and dysgeusia or dysosmia occurred with greater frequency among the participants with positive test results than in those with negative results [odds ratio (OR), 5.475; 95% confidence interval (CI), 1.960-15.293 and OR, 24.158; 95% CI, 2.693-216.720, respectively]. No significant difference was observed in the positivity rate between HCWs providing medical care for COVID-19 patients using adequate protection and other HCWs (OR, 2.514; 95% CI, 0.959-6.588). Conclusion To reduce the risk of COVID-19 spread in medical institutions, faculty and HCWs should follow standard and necessary transmission-based precautions, and those with a fever and dysgeusia or dysosmia should excuse themselves from work as soon as possible.

目的　塩味味覚閾値の高値は高血圧との関連が指摘されているが，その規定要因は明らかではない。都市部地域住民集団で塩味味覚閾値の規定要因を明らかにするとともに，複数の規定要因が同時に存在した場合の塩味味覚閾値との関連を明らかにすることを目的とした。方法　がんや循環器疾患の既往歴がなく，高血圧，糖尿病，脂質異常症の治療中ではない40～74歳の健康な都市部住民を対象としたコホート研究である神戸研究のベースライン調査参加者1,117人のうち，塩味味覚閾値検査を実施し，尿検査から推定一日食塩摂取量の結果が把握できる1,116人を対象者とした。塩味味覚閾値調査はソルセイブ®を用いて塩味味覚閾値0.6%を正常群，0.8%以上を高値群と定義した。塩味味覚閾値高値を目的変数，問診票から得られた生活状況，家族状況，教育歴，喫煙状況，飲酒状況，塩干物摂取状況，ストレス指標，推定一日食塩摂取量を説明変数として，二項ロジスティック回帰モデルにて検討した。さらに，説明変数を塩味味覚閾値に影響を与える要因，目的変数を塩味味覚閾値（正常/高値）として強制投入法を用いた多変量解析にて二項ロジスティック回帰分析を実施した。この分析では，推定一日食塩摂取量との多重共線性を考慮して，尿中ナトカリ比を除いて実施した。結果　平均年齢は男性60.9±9.0歳，女性58.0±8.7歳であった。塩味味覚閾値の正常群は80.9%（903人）（男性73.6%（251人），女性84.1%（652人）），高値群は19.1%（213人）（男性26.3%（90人），女性15.9%（123人））であった。多変量解析の結果，全対象者において現在喫煙習慣がある群は喫煙習慣が無い群と比較し，塩味味覚閾値高値となるオッズ比（95%信頼区間）が2.51（1.33-4.74）と有意な関連が認められた。また，推定一日食塩摂取量上位25%群では下位75%群と比較してオッズ比（95%信頼区間）が1.45（1.03-2.03）と塩味味覚閾値高値との有意な関連を認めた。男女別の解析では，男女ともに現在喫煙習慣と塩味味覚閾値高値との関連を認め，推定一日食塩摂取量は男性のみ関連を認めた。結論　健康な都市住民において，喫煙習慣と推定一日食塩摂取量の多さが塩味味覚閾値高値と関連していた。