• APOL1 Genotypes Not Tied to CHD in Black Women

    — But heart failure with preserved ejection fraction was an issue in postmenopausal population

    High-risk apolipoprotein L1 (APOL1) genotypes were not associated with cardiovascular disease in postmenopausal African-American women, but there was an association with hospitalization for heart failure with preserved ejection fraction (HFpEF), researchers reported.

    Analysis of data of women in the Women's Health Initiative (WHI) cohort found that high-risk APOL1 genotypes were not associated with coronary heart disease (CHD), stroke, and all-cause, and cardiovascular mortality, and that the noted link of APOL1 with HFpEF may be related to chronic kidney disease, according to Nora Franceschini, MD, MPH, of the University of North Carolina at Chapel Hill, and colleagues.

    "In this large longitudinal study of postmenopausal African-American women at risk for cardiovascular events, we confirmed the association of high-risk APOL1 status with incident ESRD [end-stage renal disease] and identified an association of high-risk APOL1 variant carriers with hospitalization for heart failure with preserved LVEF (HFpEF)," the authors wrote.

    "The main findings are also notable for the lack of association of high-risk APOL1 variant carrier status with CHD, stroke (all-cause and subtypes), mortality (all cause and cardiovascular-associated) and a composite outcome (fatal and nonfatal CHD and ischemic stroke) when accounting for known risk factors," they added.

    Of 11,137 women studied (mean age 62), the 12.3% who were carriers of high-risk APOL1variants had higher prevalence of hypertension, used cholesterol-lowering medications, and had reduced estimated glomerular filtration rate (eGFR).

    An average of 11 years later, carriers of high-risk APOL1 variants had a significant 58% increased adjusted risk of hospitalized HFpEF compared with carriers of low-risk APOL1, although they showed no differences for overall and cardiovascular associated mortality outcomes, the group wrote.

    Franceschini's group suggested that additional factors may be involved, and that variants of APOL1 may modulate furosemide-induced diuresis in heart failure.

    Adjustment for baseline kidney function also reduced the hazard ratio for ESRD among high-risk APOL1 genotypes from 1.43 (95% CI 1.01-2.02) to a non-significant 1.02.

    "This study provides new information on incidence rates of ESRD for high-risk APOL1variants in postmenopausal women, which were lower than described in population studies that combined men and women (2.6 and 3.4 per 1,000 person-years, respectively)," they wrote.

    Gregg Fonarow, MD, of the UCLA David Geffen School of Medicine in Los Angeles told MedPage Today that "Apolipoprotein L1 has some ancestry specific alleles that may play a role in the observed increased cardiovascular risk in African-American men and women. Two alleles have been previously identified to play a role in CKD in African Americans."

    "This new study of WHI participants surprisingly finds there were no significant associations of the high-risk APOL1genotypes with coronary heart disease, stroke, or cardiovascular mortality," said Fonarow, who was not involved in the study. "However, there was an associated increased risk for the type of heart failure with preserved ejection fraction. This association with heart failure may be mediated by the association of the genotype with CKD."

    Fonarow noted that "these type of studies provide important insights on potential mechanisms for race/ethnicity specific increased risk for cardiovascular diseases and stroke."

    The authors concluded that "while the function of APOL1 remains to be elucidated, these findings identify potential genetic susceptibility to detrimental consequences of kidney disease and HFpEF that disproportionately affect African-American women, as well as important information on the lack of association of APOL1 variants with CHD, stroke, and mortality in postmenopausal African-American women."

    Study limitations included the inability to assess sex differences in APOL1 risk due to inclusion of women only, participation of women only, and the inability to assess associations between APOL1 and subclinical atherosclerosis or albuminuria due to lack of such information in the WHI. The associations of APOL1 with HFpEF should be confirmed in additional studies that focus on heart morphology and function, they noted.


    The study was supported U.S. government grants.

    Franceschini and co-authors disclosed no relevant relationships with industry.

    Fonarow disclosed serving as associate editor of JAMA Cardiology and relevant relationships with Novartis.



    JAMA Cardiology

    Source Reference: Franceschini N, et al "Association of APOL1 with heart failure with preserved ejection fraction in postmenopausal African American women" JAMA Cardiol 2018; DOI:10.1001/jamacardio.2018.1827.

    Read the original article on Medpage Today: APOL1 Genotypes Not Tied to CHD in Black Women

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