Low-grade albuminuria is associated with carotid atherosclerosis in normotensive and euglycemic Chinese middle-aged and elderly adults: The Shanghai Changfeng Study



      Microalbuminuria is associated with cardiovascular disease (CVD). We investigated whether low-grade albuminuria (LGA) is independently associated with the carotid intima-media thickness (CIMT) and carotid plaques in normotensive and euglycemic Chinese middle-aged and elderly adults.


      A total of 1341 normotensive and euglycemic participants (489 males and 852 females; mean age, 57.7 years) with normal urinary albumin-to-creatinine ratios (UACRs) (<30 μg/mg) were enrolled from the Changfeng Study. A standard interview, anthropometric measurements and laboratory analyzes were performed for each participant. Bilateral CIMTs were measured using ultrasonography, and the presence of carotid plaques was assessed. The urinary albumin excretion rate was measured using an early morning urine sample to determine the UACR.


      The median UACRs were 4.2 (interquartile range, 2.9–6.0) μg/mg and 5.6 (interquartile range, 4.0–8.2) μg/mg for male and female subjects, respectively. Compared with subjects with UACRs in the first and second tertiles, subjects of both genders with UACRs in the third tertile had greater CIMTs. After adjusting for conventional CVD risk factors and the glomerular filtration rate (GFR), male and female participants with UACRs in the third tertile for each gender had a 1.696-fold and 1.911-fold increased risk, respectively, of carotid plaques relative to those in the lowest tertiles. The logUACR was positively associated with the CIMT (β = 0.068 in males, P = 0.001; and β = 0.034 in females, P = 0.012) after adjusting for conventional CVD risk factors and the GFR. The multiple logistic regression analysis showed that a 1-unit increase in the logUACR corresponded to an odds ratio (OR) of having a carotid plaque that was 1.875 (95% confidence interval (CI) 1.103–3.538; P = 0.022) and 2.389 (95% CI 1.244–4.391; P = 0.01) for male and female subjects, respectively, after adjusting for all potential confounders.


      These results suggest that the UACR is independently associated with carotid atherosclerosis in normotensive and euglycemic Chinese individuals and that even when well below the current microalbuminuria threshold, LGA contributes to the risk of atherosclerosis.


      • The study was conducted in a population with normal glucose tolerance and without hypertension.
      • The UACR was independently associated with carotid atherosclerosis after adjusting for CVD risk factors.
      • The UACR in the normal range is a novel marker or risk factor for atherosclerosis.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Wang L.
        • Kong L.
        • Wu F.
        • et al.
        Preventing chronic diseases in China.
        Lancet. 2005; 366: 1821-1824
        • Gerstein H.C.
        • Mann J.F.
        • Yi Q.
        • et al.
        Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals.
        J Am Med Assoc. 2001; 286: 421-426
        • Jones C.A.
        • Francis M.E.
        • Eberhardt M.S.
        • et al.
        Microalbuminuria in the US population: third national health and nutrition examination survey.
        Am J Kidney Dis. 2002; 39: 445-459
        • Jackson C.E.
        • Solomon S.D.
        • Gerstein H.C.
        • et al.
        CHARM Investigators and Committees Albuminuria in chronic heart failure: prevalence and prognostic importance.
        Lancet. 2009; 374: 543-550
        • Diercks G.F.
        • van Boven A.J.
        • Hillege H.L.
        • et al.
        Microalbuminuria is independently associated with ischaemic electrocardiographic abnormalities in a large nondiabetic population. The PREVEND (Prevention of Renal and Vascular ENdstage Disease) study.
        Eur Heart J. 2000; 21: 1922-1927
        • Arnlov J.
        • Evans J.C.
        • Meigs J.B.
        • et al.
        Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals. The Framingham Heart Study.
        Circulation. 2005; 112: 969-975
        • Rachmani R.
        • Levi Z.
        • Lidar M.
        • et al.
        Considerations about the threshold value of microalbuminuria in patients with diabetes mellitus: lessons from an 8-year follow-up study of 599 patients.
        Diabetes Res Clin Pract. 2000; 49: 187-194
        • Hillege H.L.
        • Fidler V.
        • Diercks G.F.
        • et al.
        Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population.
        Circulation. 2002; 106: 1777-1782
        • Romundstad S.
        • Holmen J.
        • Hallan H.
        • et al.
        Microalbuminuria and all cause mortality in treated hypertensive individuals: does sex matter? The Nord-Trøndelag Health Study (HUNT), Norway.
        Circulation. 2003; 108: 2783-2789
        • Romundstad S.
        • Holmen J.
        • Kvenild K.
        • et al.
        Microalbuminuria and all-cause mortality in 2,089 apparently healthy individuals: a 4.4- year follow-up study. The Nord-Trøndelag Health Study (HUNT), Norway.
        Am J Kidney Dis. 2003; 42: 466-473
        • Klausen K.
        • Borch-Johnsen K.
        • Feldt-Rasmussen B.
        • et al.
        Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes.
        Circulation. 2004; 110: 32-35
        • Xu J.
        • Knowler W.C.
        • Devereux R.B.
        • et al.
        Albuminuria within the "normal" range and risk of cardiovascular disease and death in American Indians: the Strong Heart Study.
        Am J Kidney Dis. 2007; 49: 208-216
        • Yuyun M.F.
        • Khaw K.T.
        • Luben R.
        • et al.
        A prospective study of microalbuminuria and incident coronary heart disease and its prognostic significance in a British population: the EPIC-Norfolk study.
        Am J Epidemiol. 2004; 159: 284-293
        • Van der Meer I.M.
        • Bots M.L.
        • Hofman A.
        • et al.
        Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam Study.
        Circulation. 2004; 109: 1089-1094
        • Gao X.
        • Hofman A.
        • Hu Y.
        • et al.
        The Shanghai Changfeng Study: a community-based prospective cohort study of chronic diseases among middle-aged and elderly: objectives and design.
        Eur J Epidemiol. 2010; 25: 885-893
        • Levey A.S.
        • Bosch J.P.
        • Lewis J.B.
        • et al.
        A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.
        Ann Intern Med. 1999; 130: 461-470
        • Li X.
        • Xia M.
        • Ma H.
        • et al.
        Liver fat content is associated with increased carotid atherosclerosis in a Chinese middle-aged and elderly population: the Shanghai Changfeng study.
        Atherosclerosis. 2012; 224: 480-485
        • Huang Y.
        • Chen Y.
        • Xu M.
        • et al.
        Low-grade albuminuria is associated with carotid intima-media thickness in Chinese type 2 diabetic patients.
        J Clin Endocrinol Metab. 2010; 95: 5122-5128
        • Stein J.H.
        • Korcarz C.E.
        • Hurst R.T.
        • et al.
        Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography. Carotid intima-media thickness Task Force Endorsed by the Society for vascular Medicine.
        J Am Soc Echocardiogr. 2008; 21: 93-111
        • Chobanian A.V.
        • Bakris G.L.
        • Black H.R.
        • et al.
        Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure.
        Hypertension. 2003; 42: 1206-1252
        • American Diabetes Association
        Standards of medical care in diabetes—2010.
        Diabetes Care. 2010; 33: S11-S61
        • Joint Committee for Developing Chinese guidelines on Prevention and Treatment of Dyslipidemia in Adults
        Chinese guidelines on prevention and treatment of dyslipidemia in adults.
        Zhonghua Xin Xue Guan Bing Za Zhi. 2007; 35: 390-419
        • Pedrinelli R.
        • Giampietro O.
        • Carmassi F.
        • et al.
        Microalbuminuria and endothelial dysfunction in essential hypertension.
        Lancet. 1994; 344: 14-18
        • Ozyol A.
        • Yucel O.
        • Ege M.R.
        • et al.
        Microalbuminuria is associated with the severity of coronary artery disease independently of other cardiovascular risk factors.
        Angiology. 2012; 63: 457-460
        • Dyer A.R.
        • Greenland P.
        • Elliott P.
        • et al.
        Evaluation of measures of urinary albumin excretion in epidemiologic studies.
        Am J Epidemiol. 2004; 160: 1122-1131
        • Ciccone M.M.
        • Scicchitano P.
        • Mitacchione G.
        • et al.
        Is there a correlation between OSAS duration/severity and carotid intima-media thickness?.
        Respir Med. 2012; 106: 740-746
        • Ciccone M.M.
        • De Pergola G.
        • Porcelli M.T.
        • et al.
        Increased carotid IMT in overweight and obese women affected by Hashimoto's thyroiditis: an adiposity and autoimmune linkage?.
        BMC Cardiovasc Disord. 2010; 28: 22