Urinary albumin excretion, even within the normal range, predicts an increase in left ventricular mass over the following 5 years
2010; Elsevier BV; Volume: 77; Issue: 12 Linguagem: Inglês
10.1038/ki.2010.8
ISSN1523-1755
AutoresThorsten Reffelmann, Marcus Dörr, Henry Völzke, Nele Friedrich, Alexander Krebs, Till Ittermann, Stephan B. Felix,
Tópico(s)Cardiac Imaging and Diagnostics
ResumoThere is increasing evidence that urinary albumin excretion, even when below the accepted threshold values for normal excretion, may have significant impact on future cardiovascular risks. To further define this, a total of 1086 patients, aged 45 years and older from the population-based, longitudinal ‘Study of Health in Pomerania’ were evaluated. Patients had echocardiographic analysis at baseline and 5-year follow-up, and were grouped into quartiles according to their baseline urinary albumin-to-creatinine ratio. At baseline, left ventricular mass in the first three quartiles was similar; however, the fourth quartile was significantly elevated and further increased over the 5-year follow-up. In the first quartile, the albumin-to-creatinine ratio and left ventricular mass did not significantly change over 5 years. In the second and third quartiles, the left ventricular mass progressively increased and was significantly correlated with the albumin-to-creatinine ratio. In multivariable analysis, this association was independent of other common cardiovascular risk factors and applicable to both genders. Our study found that the urinary albumin-to-creatinine ratio, even below the current threshold for definition of microalbuminuria, is significantly associated with increased left ventricular mass. There is increasing evidence that urinary albumin excretion, even when below the accepted threshold values for normal excretion, may have significant impact on future cardiovascular risks. To further define this, a total of 1086 patients, aged 45 years and older from the population-based, longitudinal ‘Study of Health in Pomerania’ were evaluated. Patients had echocardiographic analysis at baseline and 5-year follow-up, and were grouped into quartiles according to their baseline urinary albumin-to-creatinine ratio. At baseline, left ventricular mass in the first three quartiles was similar; however, the fourth quartile was significantly elevated and further increased over the 5-year follow-up. In the first quartile, the albumin-to-creatinine ratio and left ventricular mass did not significantly change over 5 years. In the second and third quartiles, the left ventricular mass progressively increased and was significantly correlated with the albumin-to-creatinine ratio. In multivariable analysis, this association was independent of other common cardiovascular risk factors and applicable to both genders. Our study found that the urinary albumin-to-creatinine ratio, even below the current threshold for definition of microalbuminuria, is significantly associated with increased left ventricular mass. The development of left ventricular hypertrophy (LVH) is significantly associated with the occurrence of adverse cardiovascular events, such as myocardial infarction, heart failure, stroke, and also cardiovascular mortality.1.Kannel W.B. Cobb J. Left ventricular hypertrophy and mortality – results from the Framingham Study.Cardiology. 1992; 81: 291-298Crossref PubMed Scopus (114) Google Scholar, 2.Devereux R.B. Wachtell K. Gerdts E. et al.Prognostic significance of left ventricular mass change during treatment of hypertension.JAMA. 2004; 292: 2350-2356Crossref PubMed Scopus (663) Google Scholar, 3.de Simone G. Gottdiener J.S. Chinali M. et al.Left ventricular mass predicts heart failure not related to previous myocardial infarction: the Cardiovascular Health Study.Eur Heart J. 2008; 29: 741-747Crossref PubMed Scopus (170) Google Scholar, 4.Verdecchia P. Angeli F. Borgioni C. et al.Changes in cardiovascular risk by reduction of left ventricular mass in hypertension: a meta-analysis.Am J Hypertens. 2003; 16: 895-899Crossref PubMed Scopus (251) Google Scholar Recently, various risk factors for LVH apart from arterial hypertension were identified on the basis of population-based studies and investigational trials: among others age, gender, renal function, hematocrit, and thyroid hormone status were significantly associated with left ventricular mass (LVM) in several investigations.5.Hense H.W. Gneiting B. Muscholl M. et al.The association of body size and body composition with left ventricular mass: impacts for indexation in adults.J Am Coll Cardiol. 1998; 32: 451-457Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar, 6.Henry R.M.A. Kamp O. 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Robinson D.M. et al.The association of thyroid function with cardiac mass and left ventricular hypertrophy.J Clin Endocrinol Metabol. 2005; 90: 673-677Crossref PubMed Scopus (103) Google Scholar However, when considering principles of preventive medicine, it seems to be of outstanding relevance to identify parameters, associated with further increase of LVM over time in a longitudinal study design, as these variables may become a valuable basis on which preventive measures or intensified treatment could be initiated.9.Reffelmann T. Dörr M. Völzke H. et al.Combination of electrocardiographic and echocardiographic information identifies individuals prone to progressive increase in left ventricular mass over 5 years.J Hypertens. 2009; 27: 861-868Crossref PubMed Scopus (6) Google Scholar Micro- and macroalbuminuria have long been recognized as important prognostic factors both in individuals with and without diabetes mellitus.10.Gerstein H.C. Mann J.F.E. Yi Q. et al.Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals.JAMA. 2001; 286: 421-426Crossref PubMed Scopus (1925) Google Scholar, 11.Solbu M.D. Kronborg J. Jenssen T.G. et al.Albuminuria, metabolic syndrome and the risk of mortality and cardiovascular events.Atherosclerosis. 2009; 204: 503-508Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 12.Valmadrid C.T. Klein R. Moss S.E. et al.The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus.Arch Intern Med. 2000; 160: 1093-1100Crossref PubMed Scopus (384) Google Scholar There is increasing evidence that urinary albumin excretion below currently accepted threshold values for the definition of microalbuminuria (≥2.5 mg urinary albumin/mmol creatinine for men and ≥3.5 mg/mmol for women13.European Society of Hypertension - European Society of Cardiology guidelines committee2003 European society of hypertension – European society of cardiology guidelines for the management of arterial hypertension.J Hypertens. 2003; 21: 1011-1053Crossref PubMed Scopus (3610) Google Scholar) has also significant prognostic impact with respect to several cardiovascular risk factors.10.Gerstein H.C. Mann J.F.E. Yi Q. et al.Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals.JAMA. 2001; 286: 421-426Crossref PubMed Scopus (1925) Google Scholar, 14.Ingelsson E. Sundström J. Lind L. et al.Low-grade albuminuria and the incidence of heart failure in a community-based cohort of elderly men.Eur Heart J. 2007; 28: 1739-1745Crossref PubMed Scopus (52) Google Scholar, 15.Ratto E. Leoncini G. Viazzi F. et al.Microalbuminuria and cardiovascular risk assessment in primary hypertension: should threshold levels be revised?.Am J Hypertens. 2006; 19: 728-734Crossref PubMed Scopus (18) Google Scholar In the Heart Outcomes Prevention Evaluation Study (HOPE), for example, rates of cardiovascular events and mortality increased steadily with every quartile of the urinary albumin-to-creatinine ratio (ACR).10.Gerstein H.C. Mann J.F.E. Yi Q. et al.Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals.JAMA. 2001; 286: 421-426Crossref PubMed Scopus (1925) Google Scholar Interestingly, in the first three quartiles, ACR values were far below the definition of microalbuminuria; nonetheless, the prognostic impact of ACR within these quartiles was striking. Furthermore, most of the studies, investigating the impact of urinary albumin excretion, demonstrated associations independent of common cardiovascular risk factors, which highlights albuminuria as a potential useful parameter in preventive cardiovascular medicine.10.Gerstein H.C. Mann J.F.E. Yi Q. et al.Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals.JAMA. 2001; 286: 421-426Crossref PubMed Scopus (1925) Google Scholar, 12.Valmadrid C.T. Klein R. Moss S.E. et al.The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus.Arch Intern Med. 2000; 160: 1093-1100Crossref PubMed Scopus (384) Google Scholar, 14.Ingelsson E. Sundström J. Lind L. et al.Low-grade albuminuria and the incidence of heart failure in a community-based cohort of elderly men.Eur Heart J. 2007; 28: 1739-1745Crossref PubMed Scopus (52) Google Scholar, 16.Wachtell K. Olsen M.H. Dahlöf B. et al.Microalbuminuria in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study.J Hypertens. 2002; 20: 405-412Crossref PubMed Scopus (137) Google Scholar As microalbuminuria is regarded as a sensitive indicator of a generalized vascular process with different consequences in various organs, we sought to investigate whether urinary albumin excretion is associated with the development of LVM over time. We used data from subjects aged 45 years and older of the population-based ‘Study of Health in Pomerania’ (SHIP) that provides a comprehensive set of echocardiographic investigations at baseline and at follow-up after 5 years in combination with sociodemographic, medical and laboratory parameters.17.John U. Greiner B. Hensel E. et al.Study of Health in Pomerania (SHIP): a health examination survey in an east German region: objectives and design.Soz Präventivmed. 2001; 46: 186-194Crossref PubMed Scopus (472) Google Scholar Age was significantly higher in ACR quartile IV, but similar in the first three quartiles (Tables 1 and 2). Women tended to have slightly higher urinary ACR than men (median: 0.90 mg/mmol; female 0.99 mg/mmol; male: 0.80 mg/mmol), which is reflected by the lower percentage of males in the two quartiles with higher ACR. Quartile IV (ACR>1.804 mg/mmol) differed significantly from quartile I with respect to several cardiovascular risk factors at baseline: apart from being older, subjects in this quartile were characterized by a higher prevalence of hypertension and diabetes mellitus. Accordingly, blood pressure (BP) values, frequency of antihypertensive medication, and body mass index (BMI) and glycated hemoglobin levels were also significantly higher. No significant differences were found between quartile I and II, whereas quartile III showed slightly higher BP values compared with quartile I and II. It is interesting that renal function at baseline was similar in the four quartiles; only after five years estimated glomerular filtration rate was significantly lower in quartile IV. Non-parametric correlation analysis (Spearman) revealed a significant positive correlation between urinary ACR and systolic (r=0.220, P<0.001), diastolic BP (r=0.104, P<0.001), pulse pressure (r=0.239, P<0.001), glycated hemoglobin (r=0.105, P<0.001) and BMI (r=0.129, P 0.532–0.902 (n=271)III >0.902–1.804 (n=272)IV >1.804 (n=271)P-value(n=1086)Age (years)57.8±0.5(IV)58.0±0.559.7±0.562.3±0.6(I, II, III)0.00159.4±0.3Sex (%, male)49.650.240.442.40.04445.7Arterial hypertension (%)53.356.866.281.20.00164.4Diabetes mellitus (%)7.05.211.415.90.0019.9Cigarette smoker (%)22.417.421.317.4n.s.19.6Previous MI (%)3.74.83.34.8n.s.4.2Systolic BP (mm Hg)137.6±1.2(III, IV)138.4±1.1(IV)142.4±1.2(I, IV)151.0±1.4(I, II, III)0.001142.4±0.6Diastolic BP (mm Hg)84.8±0.7(IV)85.0±0.6(IV)86.0±0.7(IV)88.5±0.7(I, II, III)0.00186.1±0.3Pulse pressure (mm Hg)52.8±0.9(III, IV)53.4±0.8(IV)56.4±0.9(I, IV)62.5±1.0(I, II, III)0.00156.3±0.5LDL cholesterol (mmol/l)3.88±0.073.92±0.073.74±0.063.87±0.08n.s.3.85±0.04HB A1c (%)5.51±0.05(IV)5.53±0.05(IV)5.61±0.06(IV)5.91±0.08(I, II, III)0.0015.64±0.03BMI (kg/m2)27.3±0.3(IV)27.7±0.228.1±0.328.6±0.3(I)0.00427.9±0.1CCl (ml/min per 1.73 m2)78.3±0.980.1±0.978.9±1.076.3±1.1n.s.78.4±0.5eGFRMDRD (ml/min per 1.73m2)74.5±0.876.1±0.874.8±0.773.5±0.8n.s.74.7±0.4Antihypertensive drugs (%)32.732.140.155.70.00140.1Diuretics (%)9.65.511.416.20.00110.7β-Blocker (%)18.018.519.123.6n.s.19.8Calcium antagonist (%)9.99.213.626.20.00114.7ACE-inhibitor (%)13.611.116.928.40.00117.4Angiotensin-II-antagonist (%)0.43.32.93.0n.s.2.4Abbreviations: ACE, angiotensin converting enzyme; ANOVA, analysis of variance; BMI, body mass index; BP, blood pressure; CCl, estimated creatinine clearance (Cockcroft Gault); eGFRMDRD estimated glomerular filtration rate (MDRD-formula); HB A1c, glycated hemoglobin; LDL, low density lipoprotein; MI, myocardial infarction; n.s., not significant.Mean±s.e.m. for continuous variables, % for frequency data. Statistics: P-value for χ2 test (numerical data) or one-way-ANOVA (continuous data) with Tukey's post hoc test for comparisons between quartiles (groups with significant differences according to Tukey's post hoc testing in superscript roman). Open table in a new tab Table 2Clinical characteristics, laboratory parameters and drug therapy after 5 years in relation to urinary albumin-to-creatinine ratio at baselineUrinary albumin-to-creatinine ratio (mg/mmol) at baseline (quartiles)Statistics (ANOVA or χ2 test between quartiles)Entire populationAfter 5 yearsI 0–0.532 (n=272)II >0.532–0.902 (n=271)III >0.902–1.804 (n=272)IV >1.804 (n=271)P-value(n=1086)Arterial hypertension (%)52.263.171.383.40.00167.5Diabetes mellitus (%)10.78.914.421.30.00113.8Cigarette smoker (%)17.314.018.114.9n.s.16.1Previous MI (%)4.47.05.97.0n.s.6.1Systolic BP (mm Hg)133.2±1.1(III, IV)135.3±1.0(IV)139.1±1.2(I)142.3±1.3(I, II,)0.001137.5±0.6Diastolic BP (mm Hg)81.0±0.681.9±0.682.4±0.681.7±0.7n.s.81.8±0.3Pulse pressure (mm Hg)52.2±0.8(III, IV)53.4±0.8(III, IV)56.7±0.9(I,II, IV)60.6±1.0(I, II, III)0.00155.7±0.5LDL cholesterol (mmol/l)3.79±0.06(IV)3.72±0.063.71±0.053.54±0.06(I)0.0223.69±0.03HB A1c (%)5.61±0.05(IV)5.60±0.05(IV)5.71±0.06(IV)5.92±0.06(I, II, III)0.0015.71±0.03BMI (kg/m2)27.8±0.3(IV)28.2±0.328.8±0.328.9±0.3(I)0.01928.4±0.1CCl (ml/min per 1.73 m2)79.0±1.2(IV)81.8±1.2(IV)78.9±1.2(IV)73.6±1.4(I, II, III)0.00178.3±0.6eGFRMDRD (ml/min per 1.73m2)76.4±1.1(IV)78.9±1.0(IV)76.0±1.1(IV)71.5±1.2(I, II, III)0.00175.7±0.6Antihypertensive drugs (%)29.433.934.250.60.00137.0Diuretics (%)10.37.712.921.80.00113.2β-Blocker (%)18.821.819.929.90.00822.6Calcium antagonist (%)7.05.57.015.90.0018.8ACE inhibitor (%)15.813.715.832.10.00119.3Angiotensin-II-antagonist (%)1.55.97.07.00.0115.3Abbreviations: ACE, angiotensin converting enzyme; ANOVA, analysis of variance; BMI, body mass index; BP, blood pressure; CCl, estimated creatinine clearance (Cockcroft Gault); eGFRMDRD estimated glomerular filtration rate (MDRD-formula); HB A1c, glycated hemoglobin, LDL, low density lipoprotein; MI, myocardial infarction; n.s., not significant.Mean±s.e.m. for continuous variables, % for frequency data. Statistics: P-value for χ2 test (numerical data) or one-way-ANOVA (continuous data) with Tukey's post hoc test for comparisons between quartiles (groups with significant differences according to Tukey's post hoc testing in superscript roman). Open table in a new tab Abbreviations: ACE, angiotensin converting enzyme; ANOVA, analysis of variance; BMI, body mass index; BP, blood pressure; CCl, estimated creatinine clearance (Cockcroft Gault); eGFRMDRD estimated glomerular filtration rate (MDRD-formula); HB A1c, glycated hemoglobin; LDL, low density lipoprotein; MI, myocardial infarction; n.s., not significant. Mean±s.e.m. for continuous variables, % for frequency data. Statistics: P-value for χ2 test (numerical data) or one-way-ANOVA (continuous data) with Tukey's post hoc test for comparisons between quartiles (groups with significant differences according to Tukey's post hoc testing in superscript roman). Abbreviations: ACE, angiotensin converting enzyme; ANOVA, analysis of variance; BMI, body mass index; BP, blood pressure; CCl, estimated creatinine clearance (Cockcroft Gault); eGFRMDRD estimated glomerular filtration rate (MDRD-formula); HB A1c, glycated hemoglobin, LDL, low density lipoprotein; MI, myocardial infarction; n.s., not significant. Mean±s.e.m. for continuous variables, % for frequency data. Statistics: P-value for χ2 test (numerical data) or one-way-ANOVA (continuous data) with Tukey's post hoc test for comparisons between quartiles (groups with significant differences according to Tukey's post hoc testing in superscript roman). At baseline, parameters of LVM assessed by echocardiography were very similar in the three lowest quartiles of urinary ACR (Figure 1). However, individuals in the highest ACR quartiles (>1.804 mg/mmol) were characterized by significantly higher LVM and LVM indices at baseline (Table 3). For the entire population, LVM increased from 187.6±1.7 g at baseline to 197.6±1.8 g over 5 years (females (n=590): 164.2±1.8 to 174.7±2.1 g; males (n=496): 215.5±2.5 g at baseline to 224.9±2.6 g after 5 years) with a mean intra-individual difference in LVM (ΔLVM) of 10.0±1.4 g (females: 10.5±1.8 g; males: 9.3±2.3 g).Table 3Echocardiographic data at baseline and 5-year follow-up in relation to urinary albumin-to-creatinine ratio at baselineUrinary albumin-to-creatinine ratio (mg/mmol) at baseline (quartiles)Statistics (ANOVA or χ2 test between quartiles)Entire populationI 0–0.532 (n=272)II >0.532-0.902 (n=271)III >0.902-1.804 (n=272)IV >1.804 (n=271)P-value(n=1086)BaselineLVd (mm)51.1±0.351.6±0.350.6±0.451.0±0.4n.s.51.1±0.2SWd (mm)9.6±0.1(IV)9.7±0.2(IV)9.7±0.1(IV)10.4±0.1(I, II, III)0.0019.9±0.1PWd (mm)9.7±0.19.6±0.1(IV)9.8±0.110.1±0.1(II)0.0289.8±0.1LVM (g)182.8±3.3(IV)186.8±3.4182.9±3.3(IV)198.1±3.6(I, III)0.004187.6±1.7LVMIBSA (g/m2)97.6±1.5(IV)99.2±1.6(IV)98.4±1.5(IV)105.8±1.6(I, II, III)0.001100.2±0.8LVMIht(g/m2.7)45.1±0.8(IV)46.2±0.8(IV)46.7±0.8(IV)50.7±0.9(I, II, III)0.00147.2±0.4FS (%)38.0±0.438.2±0.536.9±0.537.9±0.5n.s.37.8±0.2After 5 yearsLVd (mm)48.8±0.348.9±0.348.8±0.349.7±0.4n.s.49.1±0.2SWd (mm)10.7±0.2(II, III, IV)11.6±0.2(I)11.4±0.2(I)11.9±0.2(I)0.00111.4±0.1PWd (mm)9.7±0.1(III, IV)10.0±0.110.1±0.1(I)10.4±0.1(I)0.00110.1±0.1LVM (g)183.0±3.3(II, III, IV)198.3±3.5(I, IV)197.2±3.5(I, IV)211.9±3.9(I, II, III)0.001197.6±1.8LVMIBSA (g/m2)97.5±1.5(II, III, IV)104.7±1.6(I, IV)105.8±1.6(I, IV)113.4±1.8(I, II, III)0.001105.3±0.8LVMIht (g/m2.7)45.5±0.8(II, III, IV)49.1±0.8(I, IV)50.9±0.9(I, IV)54.6±1.0(I, II, III)0.00150.0±0.4FS (%)38.2±0.538.4±0.538.4±0.538.9±0.6n.s.38.5±0.3Comparison of baseline and follow-upΔ LVM (5 years) (g)0.2±2.7(II, III, IV)11.5±2.6(I)14.3±2.9(I)13.9±3.2(I)0.00110.0±1.4Abbreviations: Δ, difference; ANOVA, analysis of variance; BSA, body surface area; FS, fractional shortening; LVd, diastolic left ventricular diameter; LVM, left ventricular mass; LVMIBSA, left ventricular mass indexed by body surface area; LVMIht, left ventricular mass indexed by height2.7; PWd, diastolic thickness of the posterior wall; SWd, diastolic thickness of the interventricular septum; n.s., not significant.Mean±s.e.m. Statistics: P-value for one-way ANOVA (continuous data) with Tukey's post hoc test for comparisons between quartiles (groups with significant differences according to Tukey's post hoc testing in superscript roman). Open table in a new tab Abbreviations: Δ, difference; ANOVA, analysis of variance; BSA, body surface area; FS, fractional shortening; LVd, diastolic left ventricular diameter; LVM, left ventricular mass; LVMIBSA, left ventricular mass indexed by body surface area; LVMIht, left ventricular mass indexed by height2.7; PWd, diastolic thickness of the posterior wall; SWd, diastolic thickness of the interventricular septum; n.s., not significant. Mean±s.e.m. Statistics: P-value for one-way ANOVA (continuous data) with Tukey's post hoc test for comparisons between quartiles (groups with significant differences according to Tukey's post hoc testing in superscript roman). In individuals, presenting with a urinary ACR of ≤0.532 mg/mmol (lowest quartile), LVM did not significantly increase over 5 years (+0.2±2.7 g), whereas individuals in the other three quartiles demonstrated a substantial gain in LVM (Table 3): in women, LVM increased by +0.9±3.2 g in quartile I, but by +13.6±3.1 g, +14.6±3.4 g, and +12.0±4.2 g in quartile II–IV, respectively. In men, the difference in LVM over 5 years in quartile I was -0.6±4.3 g, but +9.5±4.2 g, +13.8±5.1 g, and +16.5±5.1 g in quartiles II–IV, respectively. After 5 years, LVM and indices of LVM in both gender subgroups and the entire population were significantly higher in the three quartiles with higher ACR in comparison with quartile I (Table 3). ΔLVM correlated significantly with urinary ACR at baseline in the entire population (P<0.001), and also in the female (P<0.016) and the male subgroup (P<0.016). When subjects with baseline urinary ACR above the gender-specific upper reference limits for the definition of microalbuminuria (females: ≥3.5 mg/mmol; males: ≥2.5 mg/mmol ACR13.European Society of Hypertension - European Society of Cardiology guidelines committee2003 European society of hypertension – European society of cardiology guidelines for the management of arterial hypertension.J Hypertens. 2003; 21: 1011-1053Crossref PubMed Scopus (3610) Google Scholar) were excluded from the correlation analysis, again, there was a statistically significant correlation between baseline ACR and ΔLVM in individuals with very low albumin excretion (females: r=0.107, P<0.017, n=501; males: r=0.105, P<0.033, n=411). By multivariable analysis (Table 4), the association between ACR (log2) and ΔLVM remained highly significant. Four different models with increasing number of potential confounders were applied (see Materials and Methods). The LVM value at the baseline was inversely correlated with ΔLVM (r=-0.319, P 140 mm Hg versus <=140 mm Hg; diastolic blood pressure >90 mm Hg versus <=90 mm Hg; and subjects on antihypertensive medical treatment and subjects without antihypertensive treatment revealed similar results. Furthermore, the association between ACR and ΔLVM was statistically significant in individuals without previous myocardial infarction (n=1031, β-coefficient (s.e.) for ACR: 2.449 (0.451), P=0.001), and in subjects without diabetes mellitus (n=969, β-coefficient (s.e.) for ACR: 2.317 (0.468), P=0.001). There was only a nonsignificant trend in subjects with diabetes mellitus (n=107, β-coefficient (s.e.) for ACR: 3.452 (1.749), P=0.051). In the entire baseline sample, restricted to subjects aged 45 years or older (n=2619, age: 61.4±0.2 years, 50.7% males), prevalence of arterial hypertension was 69.1% and prevalence of diabetes mellitus was 12.6%. Measured BP values at baseline averaged 144.3±0.4 mm Hg for systolic BP and 86.0±0.2 mm Hg for diastolic BP. Median urinary ACR (n=2193) was 1.020 mg/mmol, LDL cholesterol was 3.83±0.04 mmol/l and glycated hemoglobin was 5.71%. The LVM value at baseline amounted to 191.6±1.3 (n=1951) and LVM after 5 year was 201.0±1.6 (n=1667). In subjects with complete data for ACR and LVM at baseline (n=1616), median ACR was 0.962 mg/mmol and baseline LVM was 193.0±1.4 (n=1616), whereas LVM after 5 years in this subgroup was 197.9±1.8 g (n=1102). Thus, in comparison with individuals with complete data, as shown in Tables 1 and 2, no obvious trend toward a different profile of cardiovascular risk was apparent in the entire population aged 45 years and older, even if representativeness might be limited to a certain extent. The present analysis demonstrates a significant association of urinary ACR at baseline with increase in LVM over the following 5 years in a population-based sample of individuals aged 45 years and older. Multivariable analysis identified ACR as being independently associated with increase in LVM over 5 years among various cardiovascular risk factors. Interestingly, ACR values well below the currently recommended limits for definition of microalbuminuria were significantly associated with increase in LVM; only the lowest quartile (ACR: 0–0.532) in this population did not show significant increase in LVM over 5 years. There is increasing evidence from several clinical trials and epidemiological studies that urinary albumin excretion is significantly associated with cardiovascular events and mortality
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