biostudies-literatureLi JNIDDK NIH HHSNIEHS NIH HHSNHLBI NIH HHSMedical Research CouncilGuangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney DiseasesNational Natural Science Foundation of ChinaNational Institutes of Health374-385https://www.ebi.ac.uk/biostudies/studies/S-EPMC11599539biostudies-literatureUnknown69(4)<h4>Background</h4>The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women.<h4>Methods</h4>We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization.<h4>Results</h4>In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83-0.94]) and women (HR: 0.89 [0.83-0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74-0.89) and women (pooled RR: 0.86 [0.78-0.94]).<h4>Conclusions</h4>Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.Clinical chemistrySex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.PMC11599539MC_PC_172282019B121205005R01DK1254038207352881302417R01 DK12540381673156ES031391K23 HL140081R01 ES029082R01 ES031391ES029082MC_QA137853Zou XMadsen TEWu WCLiu JLi JZhong QManson JEZhang JZheng LChan KHKLiu SYu XfalseSex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.<h4>Background</h4>The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women.<h4>Methods</h4>We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization.<h4>Results</h4>In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83-0.94]) and women (HR: 0.89 [0.83-0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74-0.89) and women (pooled RR: 0.86 [0.78-0.94]).<h4>Conclusions</h4>Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.2023-01-01T00:00:00Z2023 Apr2025-04-04T02:33:05.148Z2025-04-04T02:33:05.148ZS-EPMC115995393670257210.1093/clinchem/hvac209