Low-Density Lipoprotein Cholesterol Attributable Cardiovascular Disease Risk Is Sex Specific.
J Am Heart Assoc
; 11(12): e024248, 2022 06 21.
Article
em En
| MEDLINE
| ID: mdl-35699189
ABSTRACT
Background Epidemiological studies show that women are generally at lower risk for cardiovascular disease than men. Here, we investigated the sex-specific differential effect of genetically increased low-density lipoprotein cholesterol (LDL-C) on cardiovascular disease (CVD) and other lipid-associated diseases. Methods and Results This is a 2-sample Mendelian randomization study that uses individual participant data from 425 043 participants from the UK Biobank, including 229 279 female participants. An 80-variant LDL-C weighted genetic score was generated. Linear and logistic regression models with interactions were used to identify differences between sex-specific LDL-C effects on lipids, carotid-intima media thickness, and multiple cardiovascular outcomes such as CVD, ischemic heart disease, peripheral artery disease, heart failure, aortic valve disease, type 2 diabetes, atrial fibrillation, and aortic aneurysm and dissection. After correction for multiple testing, we observed that the genetically increased LDL-C effect on CVD events was sex specific per SD genetically increased LDL-C, female participants had a higher LDL-C increase but an attenuated CVD risk increase compared with male participants (LDL-C female participants 0.71 mmol/L, 95% CI, 0.70-0.72 and male participants 0.57 mmol/L, 95% CI, 0.56-0.59. P for interaction 5.03×10-60; CVD female participants:
odds ratio [OR], 1.32; 95% CI 1.24-1.40 and maleparticipants:
OR, 1.52; 95% CI, 1.46-1.58. P for interaction 9.88×10-5). We also observed attenuated risks for ischemic heart disease and (nominally for) heart failure in female participants, and genetically increased LDL-C results in higher risk for aortic valve disease in female participants compared with male participants. Genetically increased LDL-C was also associated with an attenuated carotid-intima media thickness increase in female participants. We did not observe other significant attenuations. Sensitivity analyses with an unweighted genetic score and sex-specific weighted genetic scores showed similar results. Conclusions We found that genetically increased LDL-C has a sex-specific differential effect on the risk for cardiovascular disease, ischemic heart disease, heart failure, and aortic valve stenosis. Our observations provide evidence that LDL-C might be a less important determinant of CVD in women compared with men, suggesting that male patients might benefit more from LDL-C targeted therapies for CVD management than female patients and warranting investigations into the sex-specific relative contribution of risk factors for CVD.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estenose da Valva Aórtica
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Doenças Cardiovasculares
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Isquemia Miocárdica
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Diabetes Mellitus Tipo 2
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Insuficiência Cardíaca
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
J Am Heart Assoc
Ano de publicação:
2022
Tipo de documento:
Article