Urinary albumin-to-creatinine ratio levels are associated with subclinical atherosclerosis and predict CVD events and all-cause deaths: a prospective analysis

Abstract

ObjectiveWe aimed to examine the associations of urinary albumin-to-creatinine ratio (ACR) levels with risks of subclinical atherosclerosis, cardiovascular events and all-cause deaths.MethodsData from a large population-based cohort were used, which included 9580 participants aged ≥40 years free from cardiovascular diseases. Carotid intima–media thickness, brachial-ankle pulse wave velocity and ankle-brachial index were measured at baseline to assess subclinical atherosclerosis. After a median of 4.53 years’ follow-up, 486 cardiovascular events and 230 all-cause deaths were recorded.ResultsThe urinary ACR levels were categorised into three groups. Compared with the normal group (0≤ACR <7.82 mg/g), people with low-grade albuminuria (7.82≤ACR <30 mg/g) and albuminuria (ACR ≥30 mg/g) had higher levels of subclinical atherosclerosis. In prospective analysis, people with low-grade albuminuria was not significantly associated with cardiovascular events (HR=1.18; 95% CI 0.95 to 1.46], whereas people with albuminuria had a 50% higher risk of cardiovascular events (HR=1.50; 95% CI 1.11 to 2.03). People with low-grade albuminuria and albuminuria had 43% (HR=1.43; 95% CI 1.05 to 1.93) and 87% (HR=1.87; 95% CI 1.24 to 2.81) higher risks of all-cause deaths during follow-up, respectively. In stratified analysis, the association of higher ACR with risks of cardiovascular events and all-cause deaths was stronger among individuals with concomitant subclinical atherosclerosis, the presence of diabetes and more cardiovascular risk factors, respectively.ConclusionsACR levels were positively associated with subclinical atherosclerosis and predicted the risks of cardiovascular events and all-cause deaths. Evaluation of ACR levels should be integrated into risk stratification and prevention of cardiovascular events and all-cause deaths, especially among those with pre-existing subclinical atherosclerosis and cardiometabolic abnormalities.

Prevalence of Microalbuminuria and Its Association with Subclinical Carotid Atherosclerosis in Middle Aged, Nondiabetic, Low to Moderate Cardiovascular Risk Individuals with or without Hypertension

“…Microalbuminuria is still used in clinical practice; however, KDIGO guidelines recommend using the term “moderately increased albuminuria” instead of microalbuminuria [ 29 , 30 ]. In the majority of studies microalbuminuria is defined as the urinary albumin-to-creatine ratio (ACR) [ 31 , 32 , 33 , 34 , 35 ]; in other studies, it is the urinary albumin excretion (UAE) expressed as mg/24 h [ 36 ], or, as we define it, as mg/L urine, as in the PREVEND study [ 37 ]. Urinary albumin concentration (UAC) in 24 h samples is a reliable measurement in large population studies for estimating the prevalence of microalbuminuria in both sexes and irrespective of age when compared with the gold standard UAE.…”

“…Subclinical atherosclerotic status can reflect vascular injuries/endothelial dysfunction, ref. [ 35 ] which is associated with increased CV risk [ 36 ]. Several methods are used to assess vascular endothelial function, including FMD [ 36 , 44 , 45 ].…”

“…Aortic PWV is an independent predictor of CV morbidity in high-risk patients, and in the general population [ 48 , 49 , 50 ]. Albuminuria was identified as an independent risk factor for PWV [ 35 , 51 , 52 ]. Increased arterial stiffness is a major cause of a wide pulse pressure and systolic hypertension, and may contribute to glomerular damage and albuminuria.…”

“…Several studies have shown an association between ACR and peripheral artery disease (PAD), predominantly in the diabetic population [ 35 , 51 , 54 ]. We confirmed a higher prevalence of PAD in the microalbuminuric group, but no relationship was found between microalbuminuria and ABI, probably due to the fact that the diabetic population per se is more sensitive to the development of vascular damage.…”

“…An association betwen high-normal albuminuria and thickened IMT as well as a higher incidence of carotid plaque was documented in the large Japanese study with nondiabetic and nonhypertensive men [ 33 ]; it was also seen in Chinese community-based patients with T2 DM [ 54 ] and in the general population [ 63 ]. Liu et al [ 35 ], in their complex, large study with participants aged 58.2 ± 9.6 years, free from CV diseases, showed that people with low-grade albuminuria (7.82 ≤ ACR < 30 mg/g) and albuminuria (ACR ≥ 30 mg/g) had higher levels of subclinical atherosclerosis (carotid: IMT > 0.6 mm or the presence of carotid stenosis as ≥50%, elevated baPWV, but not ABI), but also higher all-cause deaths independent of glycaemic status and renal function. The association of higher ACR with all-cause deaths was stronger among individuals who had concomitant subclinical atherosclerosis, DM, or more CV risk factors.…”