Abstract
Serum uric acid (SUA) level is associated with vascular dysfunction in Eurasian populations, but little is known about this association in individuals from sub-Saharan Africa, who have a high prevalence of both relatively high SUA levels and vascular dysfunction. To assess the associations of SUA levels with macrovascular and kidney microvascular dysfunction in individuals of sub-Saharan African ancestry and evaluate potential factors that could mediate these associations. Cross-sectional analyses of baseline data from the multicenter Research on Obesity and Diabetes Among African Migrants study, conducted from 2012 to 2015, were performed from January to March 2021. The population included Ghanaian individuals living in Ghana and Europe. Abnormal SUA levels. Logistic regression was used to examine the associations of SUA level quartiles with microvascular (albuminuria) and macrovascular (peripheral artery disease and coronary artery disease) dysfunction, with adjustments for age, sex, estimated glomerular filtration rate, site of residence, socioeconomic status, alcohol, smoking, diabetes, hypertension, waist-hip ratio, and total cholesterol level. Mediation analysis was performed to assess whether the association was via elevated blood pressure, hemoglobin A1c, and high-sensitivity C-reactive protein levels or via weight-hip ratio. The research questions were formulated after data collection. A total of 4919 Ghanaian individuals (3047 [61.9%] women) aged 25-75 years (mean [SD], 46.26 [11.08] years) were included. There was a significant positive association between SUA quartiles and albuminuria, but not coronary artery disease or peripheral artery disease, after adjustment for covariates. After full adjustment, individuals in the fourth SUA quartile had higher odds of albuminuria (adjusted odds ratio [aOR], 1.54; 95% CI, 1.07-2.21), but not peripheral artery disease (aOR, 1.35; 95% CI, 0.87-2.08) or coronary artery disease (aOR, 1.09; 95% CI, 0.77-1.55), compared with individuals in the first quartile. After full adjustment, systolic and diastolic blood pressure significantly mediated the association between SUA concentrations and albuminuria, accounting for 19.4% of the total association for systolic and 17.2% for diastolic blood pressure; hemoglobin A1c, high-sensitivity C-reactive protein, and waist-hip ratio did not mediate this association. In this cross-sectional study among a sub-Saharan African population, elevated SUA levels were significantly associated with kidney microvascular dysfunction and mediated partly through elevated blood pressure. These findings suggest that individuals from sub-Saharan Africa with elevated SUA levels may benefit from periodic screening for kidney microvascular dysfunction to aid early detection or treatment.
Highlights
In the general population, atherosclerotic macrovascular diseases are common, such as coronary artery disease (CAD), peripheral artery disease (PAD), and cerebrovascular disease, and frequently complicate acute coronary syndromes, critical limb ischemia, and cerebrovascular accidents.[1,2] Likewise, microvascular disease, including nephropathy, is prevalent and remains a leading cause of kidney failure.[3]
Individuals in the fourth serum uric acid (SUA) quartile had higher odds of albuminuria, but not peripheral artery disease or coronary artery disease, compared with individuals in the first quartile
In this cross-sectional study among a sub-Saharan African population, elevated SUA levels were significantly associated with kidney microvascular dysfunction and mediated partly through elevated blood pressure
Summary
Atherosclerotic macrovascular diseases are common, such as coronary artery disease (CAD), peripheral artery disease (PAD), and cerebrovascular disease, and frequently complicate acute coronary syndromes, critical limb ischemia, and cerebrovascular accidents.[1,2] Likewise, microvascular disease, including nephropathy, is prevalent and remains a leading cause of kidney failure.[3]. Data have shown that the conventional CVD risk factors are unable to fully explain the development and/or progression of vascular dysfunction.[4] Experimental, clinical, and epidemiologic data suggest that individuals with elevated serum uric acid (SUA) levels are at increased risk of CVD and kidney dysfunction.[5,6,7,8] Most research exploring the role of SUA levels in the pathogenesis of microvascular and macrovascular dysfunction has typically excluded sub-Saharan African (SSA) ancestry populations.[5,6] Like most other vascular disease risk factors,[9] the role of SUA as a potential risk factor may be associated with race and ethnicity. We evaluated the mediating roles of hypertension, hyperglycemia, inflammation, and obesity in the association between SUA levels and macrovascular and microvascular dysfunction
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