Randi Chen, Brian J Morris, Timothy A Donlon, Kazuma Nakagawa, Richard C Allsopp, Bradley J Willcox, Kamal H Masaki
{"title":"FOXO3 长寿基因型可降低高血压对中年男性冠心病发病率造成的风险:Kuakini檀香山心脏计划","authors":"Randi Chen, Brian J Morris, Timothy A Donlon, Kazuma Nakagawa, Richard C Allsopp, Bradley J Willcox, Kamal H Masaki","doi":"10.1093/gerona/glae254","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>This study tested whether the carriage of the longevity-associated G-allele of FOXO3 SNP rs2802292 (TG/GG) protects against incident coronary artery disease (CAD) in men with hypertension.</p><p><strong>Methods: </strong>Subjects were American men residing on Oahu having Japanese (n = 5415) or Okinawan (n = 897) ancestry and free of CAD at baseline (1965-1968) when aged 45-68 years.</p><p><strong>Results: </strong>During the follow-up, there were 1 629 incident CAD cases. Adjusting for age and cardiovascular disease risk factors, the main effect Cox model showed that in men of Japanese ancestry, hypertension was a strong predictor of CAD (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.44-1.80), p < .0001), but TG/GG genotype was not associated with CAD (HR 0.92; 95% CI = 0.82-1.02; p = .11). A full Cox model showed the interaction of TG/GG with hypertension was significant (β = -0.23, p = .038). Stratified by hypertension status, TG/GG genotype TG/GG had a protective effect against CAD in each group (HR 0.83; 95% CI 0.71-0.96; p = .021 in men of Japanese heritage, and HR 0.66; 95% CI 0.43-1.01; p = .054 in men of Okinawan heritage). No association with CAD was seen in normotensive men having either Japanese (HR 1.04; 95% CI 0.89-1.22; p = .61) or Okinawan (HR 0.95; 95% CI 0.66-1.38; p = .79) heritage.</p><p><strong>Conclusions: </strong>The present prospective study found that longevity-associated FOXO3 genotype did not independently affect the risk of CAD in all men. Rather, it was associated with protection against incident CAD in men with hypertension. Hypertensive middle-aged men with FOXO3TT genotype may merit particular attention in CAD prevention programs.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11642614/pdf/","citationCount":"0","resultStr":"{\"title\":\"FOXO3 Longevity Genotype Mitigates Risk Posed by Hypertension on Incident Coronary Artery Disease in Middle-Aged Men: Kuakini Honolulu Heart Program.\",\"authors\":\"Randi Chen, Brian J Morris, Timothy A Donlon, Kazuma Nakagawa, Richard C Allsopp, Bradley J Willcox, Kamal H Masaki\",\"doi\":\"10.1093/gerona/glae254\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>This study tested whether the carriage of the longevity-associated G-allele of FOXO3 SNP rs2802292 (TG/GG) protects against incident coronary artery disease (CAD) in men with hypertension.</p><p><strong>Methods: </strong>Subjects were American men residing on Oahu having Japanese (n = 5415) or Okinawan (n = 897) ancestry and free of CAD at baseline (1965-1968) when aged 45-68 years.</p><p><strong>Results: </strong>During the follow-up, there were 1 629 incident CAD cases. Adjusting for age and cardiovascular disease risk factors, the main effect Cox model showed that in men of Japanese ancestry, hypertension was a strong predictor of CAD (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.44-1.80), p < .0001), but TG/GG genotype was not associated with CAD (HR 0.92; 95% CI = 0.82-1.02; p = .11). A full Cox model showed the interaction of TG/GG with hypertension was significant (β = -0.23, p = .038). Stratified by hypertension status, TG/GG genotype TG/GG had a protective effect against CAD in each group (HR 0.83; 95% CI 0.71-0.96; p = .021 in men of Japanese heritage, and HR 0.66; 95% CI 0.43-1.01; p = .054 in men of Okinawan heritage). No association with CAD was seen in normotensive men having either Japanese (HR 1.04; 95% CI 0.89-1.22; p = .61) or Okinawan (HR 0.95; 95% CI 0.66-1.38; p = .79) heritage.</p><p><strong>Conclusions: </strong>The present prospective study found that longevity-associated FOXO3 genotype did not independently affect the risk of CAD in all men. Rather, it was associated with protection against incident CAD in men with hypertension. Hypertensive middle-aged men with FOXO3TT genotype may merit particular attention in CAD prevention programs.</p>\",\"PeriodicalId\":94243,\"journal\":{\"name\":\"The journals of gerontology. 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引用次数: 0
摘要
本研究测试了 FOXO3 SNP rs2802292 (TG/GG)的长寿相关 G-等位基因携带者是否能预防男性高血压患者发生冠状动脉疾病(CAD)。研究对象是居住在欧胡岛的美国男性,他们有日本血统(5415 人)或冲绳血统(897 人),基线年龄为 45-68 岁(1965-1968 年),无冠状动脉疾病。在随访期间,共发现 1629 例冠状动脉粥样硬化病例。在对年龄和心血管疾病风险因素进行调整后,主效应 Cox 模型显示,在日本血统的男性中,高血压是预测 CAD 的有力因素(HR 1.61;95% CI 1.44-1.80),P<0.05。
FOXO3 Longevity Genotype Mitigates Risk Posed by Hypertension on Incident Coronary Artery Disease in Middle-Aged Men: Kuakini Honolulu Heart Program.
Background: This study tested whether the carriage of the longevity-associated G-allele of FOXO3 SNP rs2802292 (TG/GG) protects against incident coronary artery disease (CAD) in men with hypertension.
Methods: Subjects were American men residing on Oahu having Japanese (n = 5415) or Okinawan (n = 897) ancestry and free of CAD at baseline (1965-1968) when aged 45-68 years.
Results: During the follow-up, there were 1 629 incident CAD cases. Adjusting for age and cardiovascular disease risk factors, the main effect Cox model showed that in men of Japanese ancestry, hypertension was a strong predictor of CAD (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.44-1.80), p < .0001), but TG/GG genotype was not associated with CAD (HR 0.92; 95% CI = 0.82-1.02; p = .11). A full Cox model showed the interaction of TG/GG with hypertension was significant (β = -0.23, p = .038). Stratified by hypertension status, TG/GG genotype TG/GG had a protective effect against CAD in each group (HR 0.83; 95% CI 0.71-0.96; p = .021 in men of Japanese heritage, and HR 0.66; 95% CI 0.43-1.01; p = .054 in men of Okinawan heritage). No association with CAD was seen in normotensive men having either Japanese (HR 1.04; 95% CI 0.89-1.22; p = .61) or Okinawan (HR 0.95; 95% CI 0.66-1.38; p = .79) heritage.
Conclusions: The present prospective study found that longevity-associated FOXO3 genotype did not independently affect the risk of CAD in all men. Rather, it was associated with protection against incident CAD in men with hypertension. Hypertensive middle-aged men with FOXO3TT genotype may merit particular attention in CAD prevention programs.