Prevalence of Abnormal Urinary Albumin Excretion Rate in Hypertensive Patients with Impaired Fasting Glucose and Its Association with Cardiovascular Disease

ʈ Rafael Marıń,* Pilar Rodrı´guez,† Salvador Tranche,‡ Jose´Redoń,§ Francisco Morales-Olivas, Alberto Galgo,¶ Miguel A´ ngel Brito,** Javier Mediavilla,†† Jose´Vicente Lozano,‡‡ Claudia Filozof;§§ and the MAGAL group *Nephrology Service, Hospital Universitario Central de Asturias, and ‡El Cristo Health Centre, Oviedo, †Fingoi Health ʈ Centre, Lugo, §Internal Medicine Service, Hospital Clıńico, Department of Pharmacology, University of Valencia, and ‡‡Valencia Health Centre, Valencia, ¶Espronceda Health Centre and **Endocrinology, Hospital Puerta de Hierro, Madrid, ††Pampliega Health Centre, Burgos, and §§Scientific Department, Cardiovascular Section, Bristol-Myers- Squibb, Madrid, Spain

The prevalence and significance of microalbuminuria in hypertensive patients with impaired fasting glucose (IFG) has received very little attention. A total of 10,320 hypertensive patients who attended primary care centers were enrolled in this study, and the final analysis was done in 7625 patients: 1459 without IFG (plasma glucose <100 mg/dl), 3010 with IFG (plasma glucose >100 mg/dl and <126 mg/dl), and 3156 with type 2 diabetes (plasma glucose >126 mg/dl). Microalbuminuria was determined using the Micro Albustix reactive strip from Bayer (high urinary albumin excretion [UAE]: Albumin/creatinine ratio >3.4 mg/mmol). The proportion of patients with high UAE was 39.4, 48.3, and 65.6%, respectively, in the three groups (P < 0.01 for the trend). The differences in UAE between the group with IFG and the group with normal fasting glucose persisted after adjustment for age, gender, systolic BP, fasting plasma glucose, and cardiovascular comorbidity (odds ratio 1.74; 95% confidence interval 1.08 to 2.80). Hypertensive patients with IFG and high UAE showed a higher prevalence of ischemic heart disease, cardiac insufficiency, left ventricular hypertrophy, atrial fibrillation, and renal insufficiency than the group with normal UAE. Global prevalence of cardiovascular conditions was 30.4% in the group with high UAE compared with 21.4% in the group with normal UAE (odds ratio 1.60; 95% confidence interval 1.31 to 1.95). It is concluded that almost half of hypertensive patients with IFG have high UAE and a higher prevalence of associated cardiovascular involvement and renal insufficiency. J Am Soc Nephrol 17: S178–S188, 2006. doi: 10.1681/ASN.2006080912

uring the past 20 yr, epidemiologic evidence has in- Only a few studies have assessed the prevalence of mi- dicated that microalbuminuria is predictive of in- croalbuminuria in the general population (3,11,12), which D creased renal and cardiovascular morbidity and mor- ranges from 7.2 to 7.8% and can reach 16% in hypertensive tality not only in patients with diabetes but also in the general patients and even 29 to 31% in patients with diabetes. In the population (1–4). This association has proved to be indepen- Australian Diabetes, Obesity, and Lifestyle Study (AusDiab), dent of traditional risk factors such as age, BP, dyslipidemia, or the prevalence of microalbuminuria in the subgroup with dia- left ventricular hypertrophy (LVH) (5,6). These data led the betes was 21% (13). This study showed a prevalence of mi- latest report of the Joint National Committee in the United croalbuminuria of 5.1% in patients with normal fasting glucose States to accept microalbuminuria as a first-degree cardiovas- (NFG), which increased to 9.3% in those with impaired fasting cular risk factor (7). glucose (IFG; Ն110 and Ͻ126 mg/dl). This continuous and The positive association between the albumin/creatinine ra- direct relationship between urinary albumin excretion rate tio and cardiovascular and renal morbidity and mortality is (UAE) and glucose tolerance already had been reported many Ͼ evident from very low levels ( 5 mg/g creatinine), well below years before in a study that involved a very low number of the standard microalbuminuria threshold (30 mg/g creatinine) patients (14). (8,9). Recently, post hoc studies showed that the reduction in Cardiovascular risk that is associated with impaired carbo- microalbuminuria levels by therapy is associated with a reduc- hydrate metabolism (15) and microalbuminuria seems very tion in cardiovascular events (8,10). likely to increase in hypertensive patients, although this has not yet been assessed. The main objective of our study was to assess the prevalence of elevated UAE (eUAE) in hypertensive pa- Address correspondence to: Dr. Rafael Marı´n, Servicio de Nefrologı´a, Hospital Universitario Central de Asturias, C/Celestino Villamil s/n, 33006, Oviedo, tients who had IFG and attended primary care units and to Spain. Phone: ϩ34-985-108000; Fax: ϩ34-985-108015; E-mail: [email protected] compare it with the prevalence of eUAE in hypertensive pa-

Copyright © 2006 by the American Society of Nephrology ISSN: 1046-6673/1712-0178 J Am Soc Nephrol 17: S178–S188, 2006 Microalbuminuria in Hypertensive Patients with IFG S179 tients with type 2 diabetes and with those with NFG. The (lower or higher) would be estimated with more accuracy. Under this secondary objectives were to analyze the association between assumption and taking into consideration a clinically relevant differ- eUAE and other cardiovascular risk factors and to evaluate its ence of 4 to 5 units in UAE between the IFG and type 2 diabetes groups, association with cardiovascular morbidity. a total of 1600 to 2500 patients were necessary in each group to estimate this prevalence with an accuracy of between 2 and 3%, accepting an ␣ Ͻ 0.05 and a ␤ Ͻ 0.10 errors in a two-tailed P evaluation. Nevertheless, Materials and Methods with the intention of analyzing subgroups and allowing for a 25% loss MicroAluminuria en pacientes con glucemia Basal ALterada (MA- in the number of cases, the total number of patients was increased to GAL) is a multicenter, cross-sectional, observational study that was that mentioned above. carried out by 1723 primary care physicians between September and December 2005. Each physician consecutively enrolled six patients with Statistical Analyses essential hypertension in the following proportions: Three with IFG The variables are presented either as frequency and 95% CI, mean Ն Ͻ ( 100 mg/dl and 126 mg/dl), two with type 2 diabetes, and one with (SD), or median (25th to 75th percentiles) according to the distribution Ͻ NFG ( 100 mg/dl). of the variable. The t test was used for two-group comparisons, and A total of 10,320 patients were enrolled. The inclusion criteria were ANOVA was used for comparisons with more than two groups. The Ͼ Յ age 18 and 80 yr, previous diagnosis of hypertension and BP Tukey test was used to establish the difference between pairs of means Ն 140/90 mmHg, or receiving antihypertensive medication. Patients when necessary. The association between qualitative variables was with type 1 diabetes were excluded, as were pregnant or breast-feeding 2 evaluated using the ␹ or Fisher exact test. Differences were considered women; patients with urinary infection, pyuria, hematuria, or fever; significant at P Ͻ 0.05. and those who had done strenuous physical exercise during the 24 h To evaluate the factors that explained the presence of a high UAE, we before determination of microalbuminuria. constructed a multiple logistic regression model using the variables The study was approved by the Ethics and Clinical Trials Committee that were statistically significant in the previously mentioned terms. of the Hospital Central de Asturias. Informed consent of the patient Traditional risk factors also were included. The odds ratio (OR) of these was obtained in all cases. variables was reported, together with their CI and level of significance. The analysis was carried out using SAS for Windows (version 9.1; SAS Study Protocol Institute, Cary, NC). For each patient, the following were obtained: Demographic data (age and gender); clinical data (family history of premature cardiovas- Results cular disease, personal history of smoking and dyslipidemia, and pres- The final analysis was made in 7625 patients: 1459 in the NFG ence of associated cardiovascular disease [ischemic heart disease, car- group, 3010 in the IFG group, and 3156 in the type 2 diabetes diac insufficiency, cerebrovascular disease, and peripheral artery group. A total of 2695 (26.1%) were excluded for one of the disease]); and a physical examination that included weight, height, following causes of erroneous classification: Not fulfilling the body mass index (BMI), abdominal waist circumference, and systolic ϭ (SBP) and diastolic BP (DBP). Plasma creatinine, glucose, HbA , total age condition (n 357), being classified in more than one 1c ϭ cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were metabolism group (n 400), having normal BP and not receiv- ϭ measured after at least8hoffasting. UAE was determined in an ing antihypertensive medication (n 721), being included in isolated sample of first-morning urine by the semiquantitative method the normal carbohydrate metabolism group or in the IFG group using the Micro Albustix reactive strip (Bayer, Milano, Italy). For cal- and receiving antidiabetes medication (n ϭ 6 and n ϭ 674, culation of renal function, the GFR was estimated (ml/min per 1.73 m2) respectively), being in the type 2 diabetes group and having according to the abbreviated equation of the Modification of Diet in NFG with no antidiabetes medication (n ϭ 30), being in the IFG Renal Disease (MDRD) study (16). An electrocardiogram was used to group and presenting fasting glucose Ն126 mg/dl (n ϭ 318), or examine the presence of LVH (Sokolow and/or Cornell criteria) and being in the normal carbohydrate metabolism group and hav- auricular fibrillation. Similarly, we recorded patient medication data: ing HbA Ͼ7.5% (n ϭ 189). Antihypertensive drugs, antidiabetics, and lipid-lowering and anti- 1c The characteristics of the patients who were included in the platelet agents. Ͼ Sitting SBP and DBP were measured according to the recommenda- three groups are shown in Tables 1 and 2. Age was 60 yr in all tions of the Spanish Hypertension Society (Sociedad Espan˜ola de Hip- of the groups and increased progressively from NFG to diabetes. Ͼ ertensio´n) (17), after 5 min of rest and with the cuff fitted to the Mean BP was 140/80 mmHg, and a continuous and significant perimeter of the arm. Three readings were taken, and the mean value increase in SBP was observed from the normal carbohydrate me- of the last two was accepted as valid. tabolism group to the type 2 diabetes group. A BP Ͻ140/90 According to the data that were obtained using the Bayer Micro mmHg was observed in 47.4% of the patients with NFG and in Albustix reactive strips, abnormal UAE was defined as an albumin/ 42.9% of those with IFG. In the patients with diabetes, BP was Ն Ն creatinine ratio 3.4 mg/mmol (equivalent to 30 mg/g). According controlled (Ͻ130/80 mmHg) in 12.5% of cases. A progressive to the manufacturer, the Bayer Micro Albustix test has a sensitivity of increase in BMI, fasting plasma glucose, triglycerides, and creati- 90% and a specificity of 88% for the albumin/creatinine ratio. As nine also was observed from NFG to diabetes. This progressive prespecified in the protocol, urine samples with concentrations of cre- Յ increase also was verified in the associated cardiovascular mor- atinine 10 mg/dl were not analyzed because they were considered Ͻ too dilute. bidities or renal disease (defined as an estimated GFR [eGFR] 60 2 The sample size estimation was based on the 95% confidence interval ml/min per 1.73 m ). The number of antihypertensive agents (CI) of the prevalence of microalbuminuria. Because we did not know prescribed, and the use of renin-angiotensin system blockers and the prevalence of microalbuminuria among hypertensive patients with statins showed the same increasing tendency. IFG, the sample size was estimated using 50%, because any other value UAE by albumin/creatinine ratio was determined in 5288 S180 Journal of the American Society of Nephrology J Am Soc Nephrol 17: S178–S188, 2006

Table 1. Characteristics of patientsa

Characteristic NFG IFG Type 2 Diabetes

n 1459 3010 3156 Age (yr; mean ͓SD͔)b 61.6 (10.8) 62.9 (9.9) 64.7 (9.1) Male gender (%)b 47.8 48.4 48.7 SBP (mmHg; mean ͓SD͔)b 140.2 (14.2) 141.1 (13.3) 142.1 (14.2) DBP (mmHg; mean ͓SD͔) 82.3 (8.5) 82.9 (8.5) 81.7 (8.65) BMI (kg/m2; mean ͓SD͔)b 28.4 (4.2) 30.0 (4.6) 30.3 (4.6) Glucose (mg/dl; mean ͓SD͔)b 106.1 (8.2) 114.8 (6.3) 152.3 (36.5) Total cholesterol (mg/dl; mean ͓SD͔) 212.6 (34.0) 213.7 (34.4) 209.6 (38.2) HDL cholesterol (mg/dl; mean ͓SD͔) 54.9 (12.8) 53.2 (13.2) 51.0 (12.8) Triglycerides (mg/dl; mean ͓SD͔)b 134.4 (53.8) 147.6 (62.7) 163.5 (67.9) Creatinine (mg/dl; mean ͓SD͔)b 0.94 (0.21) 0.96 (0.21) 1.03 (0.26) UAE Ն3.4 mg/mmol 39.4 (36.3 to 42.9) 48.3 (46.2 to 50.5) 65.6 (63.6 to 67.5) (%; median ͓25th to 75th percentiles͔)b Cardiovascular comorbidityc 17.5 (15.6 to 19.5) 21.3 (19.8 to 22.8) 39.3 (37.6 to 41.0) (%; median ͓25th to 75th percentiles͔)b eGFR Ͻ60 ml/min per 1.73 m2 14.7 (12.7 to 16.9) 18.1 (16.6 to 19.7) 28.5 (26.8 to 30.3) (%; median ͓25th to 75th percentiles͔)b

aBMI, body mass index; DBP, diastolic BP; eGFR, estimated GFR; IFG, impaired fasting glucose; NFG, normal fasting glucose; SBP, systolic BP; UAE, urinary albumin excretion. bP Ͻ 0.01 for the linear trend. cIncluded the presence of one or more of the following conditions: Ischemic heart disease, heart failure, peripheral artery disease, and cerebrovascular disease.

Table 2. Cardioprotective therapy in each groupa

Therapy NFG IFG Type 2 Diabetes

No. of antihypertensive drugs (mean ͓SD͔)b 1.5 (0.7) 1.6 (0.7) 1.8 (0.8) Receiving ACE inhibitors, ARB, or both 75.9 (73.6 to 78.0) 77.6 (76.0 to 79.1) 88.9 (87.8 to 90.0) (%; median [25th to 75th percentile])b Use of statins 33.4 (31.0 to 35.9) 43.6 (41.8 to 45.4) 62.5 (60.8 to 64.2) (%; median [25th to 75th percentile])b Use of antiplatelet agents 15.8 (14.0 to 17.8) 22.4 (20.9 to 23.9) 50.8 (49.1 to 52.6) (%; median [25th to 75th percentile])b

aACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker. bIn all cases, P Ͻ 0.01 for the linear trend. patients (70% of the total sample). The proportion of patients higher SBP and DBP, higher creatinine, and lower eGFR were with UAE Ն3.4 mg/mmol was 39.4, 48.3, and 65.6% in the observed. There were no differences with regard to age, gender, NFG, IFG, and type 2 diabetes groups, respectively (P Ͻ 0.01 BMI, or LDL cholesterol concentrations. for the trend). The differences in UAE between the IFG group Relationship between UAE and Associated Clinical Disor- and the NFG group persisted after adjustment for age, gender, ders. Compared with those who had normal UAE, hyperten- SBP, triglyceride and glucose levels, and the number of patients sive patients with IFG and high UAE showed a greater preva- with renal insufficiency and cardiovascular comorbidity (OR lence of ischemic heart disease, cardiac insufficiency, LVH, and 1.74; 95% CI 1.08 to 2.80). atrial fibrillation. They also had a higher prevalence of renal insufficiency (19.9% [95% CI 17.5 to 22.6] versus 12.2% [95% CI Patients with IFG 10.3 to 14.3], OR 1.80 [95% CI 1.41 to 2.28]) (Figure 1). There Relationship between UAE and Target Organ Damage. In were no differences in the prevalence of cerebrovascular dis- this group, UAE was determined in 2064 patients. High levels ease or peripheral artery disease (Table 4). The global preva- (UAE Ն3.4 mg/mmol) were observed in 48.3% of cases. Table lence of cardiovascular disease was 30.4% in the eUAE group 3 shows the differences between patients with UAE and those compared with 21.4% in the group with normal UAE (OR 1.60; with normal UAE. In patients with UAE Ն3.4 mg/mmol, a 95% CI 1.31 to 1.95). This difference persisted after adjustment J Am Soc Nephrol 17: S178–S188, 2006 Microalbuminuria in Hypertensive Patients with IFG S181

Table 3. Associated risk factors in hypertensive patients with IFG according to UAEa

Risk Factor Increased UAE Normal UAE OR (95% CI)

n 998 1066 Age (yr; mean ͓SD͔) 63.3 (9.9) 63.1 (9.9) 1.0 (0.99 to 1.01) Male (%) 49.4 49.8 0.99 Family history of cardiovascular disease 9.2 (7.5 to 11.2) 7.4 (5.9 to 9.1) 1.27 (0.93 to 1.74) SBP (mmHg; mean ͓SD͔) 143.1 (14.1) 139.2 (13.3) 1.02 (1.01 to 1.03) DBP (mmHg; mean ͓SD͔) 84.1 (8.9) 82.1 (8.3) 1.03 (1.02 to 1.04) BMI (kg/m2; mean ͓SD͔) 30.2 (4.5) 30.2 (4.6) 1.00 (0.98 to 1.02) Abdominal circumference (cm; mean ͓SD͔) 100.07 (13.9) 100.56 (12.7) 0.99 (0.99 to 1.00) Glucose (mg/dl; mean ͓SD͔) 115.0 (6.3) 114.4 (6.5) 1.01 (1.00 to 1.03) Total cholesterol (mg/dl; mean ͓SD͔) 213.92 (35.6) 214.73 (34.0) 0.99 (0.99 to 1.00) LDL cholesterol (mg/dl) 132.7 (30.4) 135.2 (30.9) 0.99 (0.98 to 1.00) Creatinine (mg/dl; mean ͓SD͔) 1.00 (0.25) 0.96 (0.19) 2.29 (1.49 to 3.51) eGFR (ml/min per 1.73 m2; 73.9 (60.7 to 88.4) 75.6 (65.9 to 88.7) 0.99 (0.99 to 1.00) median ͓25th to 75th percentiles͔) UAE (mg/mmol; 6.8 (4.5 to 33.3) 1.7 (1.1 to 2.3) Ͻ0.001 median ͓25th to 75th percentiles͔)

aCI, confidence interval; OR, odds ratio.

associated with microalbuminuria, namely age, gender, SBP, BMI, and dyslipidemia (9,18), and of associated cardiovascular disease or renal insufficiency, which are known to be associated with higher levels of albuminuria. The more widespread use of cardioprotective agents in this group probably is a consequence of the higher prevalence of cardiovascular and renal disease in this group (and, therefore, higher number of drugs prescribed). The role of microalbuminuria as an early marker of renal disease in patients with type 1 and 2 diabetes is widely known. However, although the relationship between microalbuminuria and hypertension was reported for the first time Ͼ30 yr ago (19), the significance of this relationship was not recognized fully until recently, when both its prevalence and its role in coronary disease were demonstrated (20). The latest epidemiologic studies have confirmed its independent relationship with total mortality and cardiovascular morbidity and mortal- Figure 1. Cardiovascular morbidities in hypertensive patients with impaired fasting glucose according to the presence of ity both in the general population and in patients with diabetes increased urinary albumin (UAE): Proportion of patients with and high cardiovascular risk (2–6,21). Furthermore, the role of renal and cardiovascular disease. microalbuminuria in cardiovascular risk must not be considered as a categorical variable, because this risk is continuous from almost negligible levels (starting at Ͼ2 mg/g creatinine) for gender, family history of cardiovascular disease, smoking, in treated hypertensive patients (22). fasting glucose, LDL cholesterol, eGFR, and use of hypertensive Compared with patients without diabetes, patients with type agents and/or statins (OR 1.42; 95% CI 1.08 to 1.88). 2 diabetes have a two to four times higher cardiovascular risk. Several studies have analyzed the possible existence of a Discussion threshold between fasting glucose and cardiovascular disease. This is the first study in Spain to analyze the prevalence of This relationship appears at low levels of fasting plasma glu- eUAE in hypertensive patients with IFG. The results show that cose, including those that are considered as IFG (100 to 125.9 this prevalence reaches almost half the population studied with mg/dl), especially in patients with impaired glucose tolerance intermediate values between the two control groups: Hyper- (23–26). Our study showed that the progressive deterioration in tensive patients with NFG and hypertensive patients with as- carbohydrate metabolism is related directly to both nonmodi- sociated type 2 diabetes. fiable (age and male gender) and modifiable risk factors (SBP, This increased prevalence of UAE in patients with IFG was BMI, and triglycerides) and confirmed their relationship with a independent of other risk factors that traditionally have been greater presence of cardiovascular events. Few studies have S182 Journal of the American Society of Nephrology J Am Soc Nephrol 17: S178–S188, 2006

Table 4. Associated cardiovascular disease in hypertensive patients with IFG according to UAE

Increased UAE Normal UAE OR Cardiovascular Disease (% ͓95% CI͔) (% ͓95% CI͔) (95% CI)

Ischemic heart disease 11.7 (9.8 to 13.9) 8.0 (6.4 to 9.8) 1.53 (1.14 to 2.06) Left ventricular hypertrophy 12.4 (10.4 to 14.6) 7.8 (6.2 to 9.6) 1.68 (1.25 to 2.25) Heart failure 6.2 (4.8 to 7.9) 2.7 (1.8 to 3.9) 2.37 (1.51 to 3.71) Atrial fibrillation 4.6 (3.4 to 6.1) 1.8 (1.1 to 2.8) 2.66 (1.55 to 4.57) Peripheral artery disease 6.5 (5.1 to 8.2) 5.1 (3.8 to 6.6) 1.30 (0.90 to 1.89) Cerebrovascular disease 3.8 (2.7 to 5.2) 3.7 (2.7 to 5.1) 1.01 (0.65 to 1.60) Associated cardiovascular diseasea 30.4 (27.5 to 33.3) 21.4 (19.0 to 24.0) 1.60 (1.31 to 1.95) eGFR Ͻ60 ml/min per 1.73 m2 19.9 (17.5 to 22.6) 12.2 (10.3 to 14.3) 1.80 (1.41 to 2.28)

aIncluded the presence of one or more of the following conditions: Ischemic heart disease, heart failure, peripheral artery disease, and cerebrovascular disease. assessed the relationship between renal disease and glucose Ͻ60 ml/min per 1.73 m2 is an independent risk factor for total tolerance (13,27). Despite that renal disease is well recognized mortality, cardiovascular events, and hospitalization (32). Ther- in hypertensive patients—even more so in patients with dia- apeutic intervention studies with UAE-reducing agents such as betes—it has been less acknowledged in patients with IFG. angiotensin II receptor blockers have proved to be effective in In our study, the prevalence of high UAE was greater than reducing vascular morbidity in hypertensive patients without that reported in the Third National Health and Nutrition Ex- diabetes and the progression of renal disease in type 2 diabetes amination Survey (NHANES III) population studies (14) or in (2,10). This medication must form part of a multifactorial strat- studies in the population with diabetes that were carried out in egy. In patients with several risk factors, antihypertensive Australia or Italy (11,13,28). This may be related to the presence agents, statins, antiplatelet agents, and, when necessary, oral of arterial hypertension, older age, and a different method of antidiabetes medication or insulin should be included. Early detecting UAE. initiation of microalbuminuria-lowering drugs should form To date, no published studies have analyzed specifically the part of the therapeutic arsenal in patients with a high vascular significance of the high UAE in hypertensive patients with IFG, risk (33). who already have a high vascular risk. The additional presence Our study has several limitations. First, UAE was determined of a high UAE was associated directly with BP and with gly- in only one sample. Although this is common in epidemiologic cemia and creatinine levels. Emphasis must be placed on its studies (11,13), clinical practice requires at least three samples association with intermediate variables (LVH and atrial fibril- (two of these with high values) to establish the diagnosis. Our lation) and, more important, with a greater prevalence of global single measurement does not allow us to accept conclusively cardiovascular morbidity, specifically coronary disease and car- the diagnosis of microalbuminuria. Second, determination of diac insufficiency. This association persisted after adjustment the albumin/creatinine ratio by the reactive strip that was used for the presence of other traditional cardiovascular risk factors in the semiquantitative method is less widely known, although and drugs that can modify UAE, such as angiotensin-convert- a recent study with a series of 24,000 patients used this tech- ing inhibitors, angiotensin II receptor blockers, or statins. The nique (34). Our study also is limited by its cross-sectional and greater prevalence of renal insufficiency also was significant. Prediabetic patients, such as those who were analyzed in our multicenter design, although the size of the sample can reduce study, have an increased risk for coronary disease also de- potential bias. Furthermore, the prevalence of some potentially scribed in patients with high UAE. Microalbuminuria, IFG, and life-threatening cardiovascular events (e.g., stroke, myocardial arterial hypertension form part of the so-called metabolic syn- infarction) cannot be included in this type of design and may drome, which has been recognized as a favorable condition for alter the true magnitude of associated cardiovascular disease. greater prevalence of cardiovascular disease and chronic renal disease (29,30). The pathogenic connection among microalbuminuria, IFG, and hypertension is not known but may reflect Conclusion the presence of generalized vascular lesions that are increased Hypertensive patients with IFG show higher UAE than hy- by each of these processes individually. Microalbuminuria is pertensive patients with NFG and, consequently, a greater considered a marker of endothelial dysfunction, favoring ath- prevalence of associated cardiovascular disease and renal in- erosclerosis and cardiovascular morbidity. Even in patients sufficiency. Early and multifactorial therapeutic intervention without diabetes, microalbuminuria also may be an expression including a strict control of BP and renin-angiotensin system of the same degree of glomerular capillary dysfunction. Some blockers can prevent or defer vascular/renal morbidity and studies in patients with essential hypertension have shown that mortality in this type of patient. Nevertheless, long-term, pro- high UAE is a predictor of future deterioration of renal function spective studies with a more accurate method of detecting UAE (31). Furthermore, several recent studies showed that a GFR of are warranted to corroborate our results. J Am Soc Nephrol 17: S178–S188, 2006 Microalbuminuria in Hypertensive Patients with IFG S183

Acknowledgments Bonet Garcia Jorge, Bordallo Huidobro Juan Ramoń, Bordas Ignacio, This study was supported by a grant from Bristol-Myers-Squibb, Borges Mesa Ofelia, Borrachero Carmen, Borras Palle Carlos, Botella a Madrid, Spain. Gregori Ana, Bouzas Formoso Fernando, Bravo Bricien M Luz, Bravo The following investigators participated in the MAGAL Study: Valverde Antonio, Brime Secades Jose´ Manuel, Brito Brito Elisenda, a Abarca Bujan Benjamıń, Abordan Chanat Ruchdi Omar, Acosta Meń- Brito M Jesu´s, Buendıá Romero Alejandro, Bueno Lozano Mercedes, dez Juan M., Acosta Socorro Antonio, Adelantado Pozuelo Esther, Buitrago Vera Carmen, Burgui Eslava Antonio, Busselo Lete Luis Afonso Navarro Carmen, Agote Cuesta Gabriel, Aguado Mori Ana Miguel, Bustamante Caso Maria Luisa, Caamanõ Mata Juan, Cabal Cristina, Agudo Codujoń Beatriz, Aguilar Huertas Eva, Aguilera Zu- Garcia Alberto, Cabaleiro Ubeira Dolores, Caballero Millan Pilar, Ca- bizarreta Eulalia, Aguilo´ Furio´ Sara, Aguirre Minãna Teresa, A´ lamo ballero Montanary Leońides, Cabanes Martıń Teodorico, Cabanilla ´ Domıńguez Anı´bal, Alba Dıáz A´ ngel, Albert Cunãt Vicente, Albors Valenzuela Antonio, Cacho Angel, Cal Martıńez Pablo, Calatayud Car- a Valls Alberto, Alegret Crespi Santiago, Alegria Alonso Ramoń, Alfaro reres M Del Carmen, Calatayud Climent Enrique, Calatayud Climent a Alonso Guillermo, Alfaya Carrera Juan Jose, Allut Vidal Germań, Enrique, Caldeiro Jimeńez Jose´M, Calderoń Alva Juan, Calduch Her- Almela Tejedo Teresa, Alonso Atienza Ma Del Carmen, Alonso Del rera Lourdes, Calero Gonzalez Cloria, Callado Ramoń Mariano, Calleja a Pino Elena, Alonso Dıáz-Marta Manuel, Alonso Fernandez Lola, Delgado M A´ ngeles, Calvillo Navarro A´ ngel, Calvinõ Carballo Alonso Matia Rafael, Alonso Quintanilla Carmelo, Alonso Patricio, Ramoń, Calvo Hornillos Mercedes, Calvo Quintela Laura, Calzada Gil a Altarriba Cano Ma Luisa, Altuna Zuriarrain Manuel, Alvarado Tato Manuel, Camarena Rodrı´guez Jose´M, Campos Martos Ignacio, Can- Antonio M., A´ lvarez Blanco Antonio, A´ lvarez De Monrego Carina, dau Marcos Rafael, Candela Maetzu Macarena, Caneda Carmen, Ca- A´ lvarez Fernandez Hortensia, A´ lvarez Garcıá Antonio, A´ lvarez Guisa- neiro Lo´pez Ana Maria, Caniego Monreal A´ ngel, Cano Aparicio Pere, sola Fernando, A´ lvarez Mejorada Enrique, A´ lvarez Sanchez Ignacio, Cano Espıń Agustina, Cantera Valls Nieves, Canãs Gonzalez Juan, A´ lvarez Taboas Jorge, A´ lvarez Valero Jesu´s, A´ lvarez Vicente Juan Capdevila Falguera Dolors, Carballal Martıńez Angelines, Carballo Carlos, Alvear Garcıá Martin Jorge, Amhed Loufty Kheder, Amigo Albarate Jose Luis, Carballo Garcia Jose Juan, Carcas Sansuan Jose´Luis, a Nuń˜ezMa Elena, Amurrio Olartua Juan Ma, Andre´s Pauls Inmaculada, Carcedo Sua´rez Virgilio, Ca´rdenas Joyanes M Dolores, Cardona Ros- Andre´s Mayor Ma Jose´, Andre´s Santos Esther, Andreu Amoros Juan sello Federico, Carmona Segado Jose Manuel, Carrasco Go´mez Conso- Luis, Angel Cavada Miguel, Angora Mazuecos Francisco, Anguiano lacioń, Carrasco Herrera Jesu´s, Carrasco Pineda Marcos, Carretero Calvo Jose´, Angulo Gonzalez Javier, Angulo Vallejo Ester, Angulo Ramos Raquel, Carretero Salvador Olegario, Carrillo Lourdes, Carrio Yuste Enrique, Antolin Llinares, Asuncioń, Anton Ortega Javier, Antoń Garcia Guillermo, Carrioń Valero Lucinio, Carvajal Trujillo Nicomedes, Castello´ Jose´ Luis, Antoń Garcıá Francisco, An˜el Rodrı´guez Rosa, Casal Ardines Eliecer, Casal Osorio Antonio, Casal Redondo Fernando, a a Aramburu Aramburu Pedro, Arancegi Marticorena Izaskun, Arayo Casanova Carlos, Casanueva A´ lvarez Rosa M , Cascan Martıń Jose M , Sola Inmaculada, Arbesu´Prieto Jose´, Arde´vol Gonza´lez Ro´mulo, Are- Castanõ Gonza´lez Mercedes, Castell Victoria, Castello Esteve Luis, a nas Mosqueda Juliań, Arias Go´mez Ma Jesus, Arias Salgado-Robsy Ana Castillejo Orozco Ana E, Castresana Arrate M Victoria, Castro Blanco Marıá, Ariza Hernańdez Andre´s, Arlandis Puig Antonio, Arnal Isabel, Catalań Macia´ Jose´, Catoń Valde´s Manuel, Cavero Clerencia Sanchez Jose, Aroca Sanz Ma Luisa, Arocas Pe´rez Ricardo, Arribas Elena, Cazador Romero Pilar, Cebreiro Navalon Antonio, Cebrian Aguirregavirıá F. Javier, Arrieta Ma Jesu´s, Arrondo Beguiristain Ma Montolio Francisco, Cebrian Picazos Adolfo, Cejudo Serrano Rosa, A´ ngeles, Arroyo Azpa Concepcioń, Arteaga Herrera Domingo, Arteche Celades Moliner Pilar, Cenoz Osinaga Juan Carlos, Cerdan Oliver Legorburu Miguel A´ ngel, Artigues Llull Isabel, Arujo Marisol, Arza Miguel, Cereceda Pecilla Ricardo, Cervantes Chaves Alfredo, Cervera Arteaga Alicia, Ascanio Leoń Beleń, Asenjo Cabrera Irene, Asenjo Moscardo Jose B, Chumilla Checa Celia, Cifuentes Go´mez Pedro, Cir- Martin Amparo, Asensi Penãrrocha Isabel, Atienza Gaona Jose Juan, apozu Mendivil Juan, Cobo Domıńguez Concepcioń, Cobo Rodrigo Atxotegi Loizate Laura, Auza Jose´ Javier, Avile´s Martıńez Francisco Ammonia, Codesido Blanco Teresa, Colomer Escuder Teresa, Colomer Javier, Ayala Munõz Francisco, Ayensa Esparza Javier, Aznar Ladroń Lloret Mireya, Colomina Sarrio´ Pilar, Comas Samper Jose Manuel, De Guevara Ma Jose, Azorıń Sanz Francisco Javier, Baamonde Concheiro Coello Gonzalo, Contrera Enrique, Contreras Torres Juan A, Mosquera Leopoldo, Badiola Elu Jose Luis, Badosa Sanuy Ana, Baeza Copeiro Del Villar Martıńez Ana, Corell Dolz Jose´, Coronado Reyes Romero Manuel, Baixarias Tibau Joaquim, Bajo Garcia Juliań, Balaguer Pedro, Corralez Hava Joaquin, Correa Armero Rosario, Corte´s Oliva Montesinos Francisco, Balanzategi Garmendia Inmaculada, Ballester Anna, Cortilla Santamaria Albert, Cozar Hernandez Antonio, Crespo Berenguer Jose´ Vicente, Ballester Dıáz Trinidad Margarita, Ballester Basterra Javier, Crespo Gargallo Antonio, Crespo Jimenez Floreal, Cre- Orti Javier, Banõń Garcıá Raquel, Banõs Martıńez Ma Soledad, Banõs spo Martıńez Francisco, Crespo Rodrı´guez Rufina, Criado Gonzalez Merino Isabel, Ban˜uelos Gago Ma Jesu´s, Barbeito Zaldua Edurne, Bar- Luis, Cristobal Torras Joan, Cruz Villegas Inmaculada, Cubas Cubells celo´Bartolome´, Barges Ponce Vicente, Barras Galań Domingo, Barreiro Carmen, Cuende Chamorro Maria Jesu´s, Cuerpo A´ lvarez Francisco, Mourentans Carlos, Barrera Pe´rez Manuel, Barrera Torres Vicente, Cueto Bulnes Ignacio, Cumplido Pe´rez Antonio, Damas Manuel, Dap- Barruso Bares Carlos, Bartolome´ Resano Javier, Bartolome´ Resano ena Baroń Cristina, Davila Brun Carlos, De Diego Sierra David, De Rafael, Baudet Dejean Chantal, Beaus Alonso Jose´Luis, Becerra Becerra Felipe Medina Ricardo, De Frutos Marcos Concha, De La Fuente Fer- Alberto, Belayos Jimeńez Enrique, Belenguer Ma´rquez J.Maria, Belen- nańdez Teodoro, De La Fuente Marinõ Rosa, De La Torre Edo Jorge, De guer Prieto Rafael, Belles Calvo Amadeo, Belmonte Santamarıá Julia La Vega Cuya´s Arturo, De La Villa De Diego Ricardo, De Miguel Elena, Beltrań Juana Jose, Benavides Fernańdez Encarnacioń, Benedicto Villamediana Begonã, De Simoń Gutie´rrez Rau´l, Debon Belda Manuel, Acebo Rosa, Benedito Garcıá Esther, Bengoa Goiri Ainhoa, Bengoetxea Dehesa Terreros Jose´, Del A´ lamo Alonso Alberto, Del Alba Carballo Zorrilla Juan, Benı´tez Ortiz Juan Pedro, Benı´tez Rivero Javier, Benito De Maria Rosa, Del Amo Rodrı´guez Concha, Del Amo Carmen, Del La Cruz Jose´-Luis, Benlloch Guillem Jose´Blas, Berciano Ma´rquez Edu- Campo Aguado Concepcion, Del Carmen Elcuaz Juliań, Del Castillo ardo, Bermejo Enjuto Carmen, Bermejo Garcia Begonã, Bermejo Guilleń Martıńez Ma Jose´, Del Jesu´s Clemente Amelia, Del Rivero Llano En- Gonzalo, Bernad Guerrero Amparo, Bernal Soto Jose Antonio, Bernat rique, Dela´s Go´mez Enrique, Delfin Va´zquez Marta, Delgado Gil Luis Marcial, Besada Gesta Ricardo, Bethencourt Marante Jorge, Dominguez Benito, Diaz Bernabe´Jose´Ramoń, Diaz Fernandez Ma Del Bijedick Snejada, Bilbao Armas Inãki, Blanco Aparicio Javier, Blanco Carmen, Diaz Gomez Juan Manuel, Diaz Millań Almudena, Diaz Olea Arias Ana, Blanco Perdigoń Luis, Blanco Ramos Cristina, Blanco Ro- Emilia, Diaz Roger Teresa, Dıáz Andre´s Ma Luisa, Dıáz Eraso Mont- drı´guez Rubeń, Bocos Ruiz JoseÍgnacio, Bolinches Gandia Juan Jose, serrat, Dıáz Jimeńez Jesu´s, Dıáz Luis Carmen, Dieguez Estevez S184 Journal of the American Society of Nephrology J Am Soc Nephrol 17: S178–S188, 2006

Agapito, Diez Blanco Felipe, Diez Garcia Manuel, Diez Ruiz Ana, Dıéz Garrido Marcos Cecilio, Garrote Florencio Timotea, Garrote Gutierrez Cantalapiedra Eladio, Dıéz Cantarero Adolfo, Dimas Nun˜ez Fernando, Luis, Gascon Boto Fatima, Gasso Jimeńez Jose´ Manuel, Gazquez In- Divison Garrote Juan Antonio, Doíaz Ruisanchez Enrique, Domingo maculada, Genoves Esplugues Andres Vicente, Gerpe Rodriguez Os- Platero Concepcion, Domingo Sancho Cesar, Dominguez Gonzalez car, Gijon Conde Teresa, Gil Correa Leopoldo, Gil Gil Cecilio, Gil Jesus, Domıńguez Deben Daniel, Domıńguez Pe´rez Juan A., Dosantos Munõz Julio, Gil Prats Pedro, Gil Tocados Guadalupe, Gil Velez Jaime, Hernandez Javier, Echeverria Arruabarrena Juan, Eguinoa Villanueva Gili Juan, Gimeńez Gonza´lez Manuel, Gobierno Hernańdez Jesu´s, Jose´Luis, Eiris Cambre M.Jesu´s, Ekek Jannura Miguel, El Kak Chaaban Godoy Garcıá Isidro, Goenaga Badiola Eugenia, Goikoetxea Arrillaga Raffat, Eliche Vilchez Juliań, Elorriaga Campos Angel, Elorriaga Alejandro, Golpe Dıáz Marcos, Gomez Abellas Enrique, Gomez Agui- Urquijo Eguzkin˜e, Elorza Olabegoya Itziar, Elvira Perez Eladio, Enci- naga Juan Manuel, Gomez Albadalejo Eduardo, Gomez Criado Maria noso Sańchez Candelaria, Enrriquez De Terry Alfonso, Epaizabal Mu- Soledad, Gomez Dacal Maria Dolores, Gomez Galvez Cayetano, Gomez jika Xabier, Erdozain Corpas Juan Pedro, Erlanz Abad Arturo, Escobar Garcia Beatriz, Gomez Queipo Belen, Gomez Rodriguez Adela, Gomez Moreno Cesar, Espinosa Barrientos Lourdes, Estarriol Jimeńez Carlos, Saez Miguel A´ ngel, Gomez Sal Esther, Gomez Vazquez Jose Luis, Esteban Gaitero Juan Pedro, Esteban Marquez Juan Jose´, Estebanez Gomez Sonsoles, Go´mez Del Rıó Marıá Zulema, Go´mez Marcos Man- Auxina Alberto, Esteve Fuster Vicente, Este´vez Ardit Anabel, Este´vez uel A´ ngel, Go´mez Marıń Elisa, Gonzalez Aller Manuel, Gonza´lez Gonza´lez Pablo, Etxeberria Uribesalgo Carmelo, Etxevarria Etxevaria Acunã Eduardo, Gonzalez Alvarez Antonio, Gonzalez Candela Rosa, Juan Ignacio, Etxezarreta Crespo Ramon, Ezpeleta Albuixech Leo- Gonzalez Espadas Ricardo, Gonzalez Gordillo Soledad, Gonzalez Her- nardo, Farouk Hendi Malas Mohamer, Farreres Pı´ Concepcio´, Faus nańdez Luis, Gonzalez Loureiro Patricia, Gonzalez Lujan Jose´ Luis, Mascarell Emilia, Fenoll Pascual Federico, Fenoy Soriano Angel, Fer- Gonzalez Marcos Juanjo, Gonzalez Martin Carmen Teresa, Gonzalez nańdez Benitez Carlos, Fernandez Cabello Ma Luisa, Fernandez Canã- Perez Carmen, Gonzalez Perez Ma Jesu´s, Gonzalez Ramos Elena, das Enrique, Fernandez Fernandez Carmen, Fernandez Fernandez Le- Gonzalez Reza Emilio, Gonzalez Rodriguez Manuel, Gonzalez Vicente andro, Fernandez Fernandez Luis, Fernandez Gomez Jose, Fernandez Angel, Gonza´lez Aguado Jose´ Manuel, Gonza´lez Casado Ignacio, Hernandez Jose A´ ngel, Fernańdez Lo´pez Jose´Manuel, Fernandez Mar- Gonza´lez Delgado Federico, Gonza´lez Fernańdez Maximino, Gonza´lez tinez Angel, Fernandez Martinez Juncal, Fernandez Moyano Fernando, Gago JoseÁntonio, Gonza´lez Garcia Angel, Gonza´lez Garcia Carmen, Fernandez Peleteiro Jose Manuel, Fernandez Seoane Antonio, Fernan- Gonza´lez Hernańdez JoseÁ., Gonza´lez Martin Angela, Gonza´lez Mar- dez Silva Ma Jesus, Fernandez Villaverde Jose Maria, Fernandez Yebra tin Carmen Teresa, Gonza´lez Meńdez Magdalena, Gonza´lez Pozueco Esther, Fernańdez Arienza Jose´, Fernańdez Barrial Manuel, Fernańdez Yolanda, Gonza´lez Rodriguez Emilio, Gonzalez-Vals Gonzalez Ma Jose, Canãveras Ma Isabel, Fernańdez Escalada Eugenio, Fernańdez Garcia Gonzalo Ines, Gorostiza Ormaetxea Javier, Gorrocategui Erenõ Jesus, Elisa, Fernańdez Garcia Jose Maria, Fernańdez Gonza´lez Angeles, Fer- Granado Sanchez Francisco Jose´, Granja Garrań Yolanda, Gregori Pel- nańdez Gonza´lez Manuel, Fernańdez Gutie´rrez Maria A´ ngeles, Fernań- licer Juan-Ignasi, Guerrero Espejo Ma Carmen, Guija Villa Eduardo, dez Mourinõ Ma Jesu´s, Fernańdez Prieto Dulce, Fernańdez Roces Ra- Guillard Marie Martine, Guillen Hernandez Gaspar Elias, Guillot Valls monita, Fernańdez Rodriguez JoseÁntonio, Fernańdez Sańchez Carlos, Alfonso, Guinot Martinez Enrique, Gutierrez Angulo Marisa, Gutierrez Fernańdez Simoń Felisa, Ferrandiz Miquel Joaquin, Ferrandiz Miquel Espinosa de los Montero Juan Antonio, Gutierrez Marin Francisco, Joaquin, Ferreiro Alonso Pablo, Ferreiro Guri Jose Antonio, Ferrer Gutierrez Moreno Jose Abel, Gutierrez Miguel A´ ngel, Haya Guaita Bascunãna Pedro, Ferrer Tomas Ramon, Fiallega Otero Rafael, Flores Amparo, Hermosa Hernan Juan Carlos, Hernaiz Valero Susana, Her- Hernandez Miguel Angel, Flores Holguera Antonio, Flo´rez Garcia Jose´, nandez Inãrra Gabriel, Hernandez Manzano Carmen, Hernandez Mar- Florit Anglada Antonio, Font Servera Jose, Forcada Lozano Eugenio, tin Francisco Javier, Hernandez Mayle Colette, Hernańdez Gutie´rrez Formento Tirado Aurelio, Fraga Cabado Jose´, Fraga Carballo Carmen, Juana Isabel, Hernańdez Ollero Ma Dolores, Hernańdez Perlines Ma Fraga Gonzalez Camila, Franco Martinez Generosa, Fransi Galiana Vicenta, Hernando Mendivil Itziar, Hernando Zapatero Carlos, Her- Amparo, Frasquet Todolı´ Concha, Fuentes Fernandez Fernando, Fu- nani Bengoa Marta, Herraiz Rodriguez Ramoń, Herrera Pelaez Anto- entes Vigil Jose´, Fuster Bellido Toma´s, Gabriel Escribano Ma A´ ngeles, nio, Herrera Valladolid Carmen, Herrero Ballestar Jose Vte, Herrero- Gacto Fernandez Socorro, Gadea Vicente Pilar, Gaga Garcia Alfredo, zorriqueta Ma Jesu´s, Hervias Saiz Francisco Jose´, Hevia Rodriguez Gago Fernańdez Carlos, Gainza De Los Rios Luis, Gaisań TomeĆar- Eduardo, Hidalgo Herrera Manuel, Homar Isern Bernardino, Hortal men, Galań Velasco Jose´ Antonio, Galarreta Calvo Javier, Galarza Gutierrez Felicidad, Iban˜ez Bernabeu Vicente, Iban˜ez Gomez Patricia, Amorrortu Ana, Galdamez Nun˜ez Ana Ma, Galindo Tobal Francisca, Ibarra Corbilloń Angel, Ibeas Cristina, Iglesias Clemente Jose´M., Igle- Gallardo Alonso Fernando, Gallego Berciano Pilar, Gallego Garcia Car- sias Perez Eugenia, Iglesias Retamar Rafael, Igual Fraile Dimas, Ilizarri men, Gallo Trebol Fernando, Gallo Jaime, Gamarra Ortiz Javier, Ollauri Miren, Indurain Ordunã Santos, In˜igo Espinosa Pedro A., Isidro Gamero Perez Florencio, Gandia Moya Carmen, Garay Orte Jon, Ga- Ortega Joan, Iturralde Iriso Jesus, Iturri Gaztelu Ana, Iznaola Sanchez rayoa Arraiza Javier, Garcia Andre´s Luis Enrique, Garcia Blas Miguel, Pedro Juan, Izquierdo Lopez Enrique, Izquierdo Sanz Jose Ramoń, Garcia Cabarcos Juan Antonio, Garcia Campo Urbano, Garcia Cantos Izquierdo Yan˜ez Ma Jose´, Jalon Monzon Mercedes, Jamil Ala Ramzi, Elena, Garcia Castellanos Natividad, Garcia Cuadros Marta, Garcia De Jesu´s Casado Maria, Jimenez Perez Ramon, Jimeńez Franco Julio, Jime´- Francisco Ana, Garcia Exposito Esmeralda, Garcia Falide Nieves, Gar- nez Paredes Javier, Jimeńez Redondo Jose´Ramoń, Jorge Bravo Maria cia Gallego Francisco, Garcia Gonzalez Carmen, Garcia Lombardero Teresa, Jorge Rodriguez Fco.Jose, Jorques Navarro Juan Daniel, Jover Jose Maria, Garcia Machado Ma Luisa, Garcia Martinez Jose Joaquıń, Barber Juan Manuel, Juan Armas Julia, Juanes De La Penã Adriań, Garcia Molinos Juan R, Garcia Nadal Ignacio, Garcia Ortiz Jose Pablo, Jurado Toro Alberto, Labrador Gonzalez Alberto, Labrador Esther, Garcia Ortiz Luis, Garcia Ortiz Teresa, Garcia Panero Maria Luisa, Lado Llerena Angel, Lado Lopez Manuel, Laencina Lo´pez Salvador, Garcia Perez Rafael, Garcia Pe´rez Fina, Garcia Pindado Ma A´ ngeles, Lafuente Gutie´rrez Jose Luis, Laguna Isabel, Lalanza Lasheras Juan Garcia Prades Pascuala, Garcia Ramoń Elpidio, Garcia Romanos Fer- Jose, Lamelas Garcia Jose A., Landin Vicunã Concha, Laporta Crespo nando, Garcia Sanchez Dolores, Garcia Sanchez Sofia, Garcia Serrano Felix, Lara Moles Jesu´s, Larrinaga Kortabitarte Aitor, Lasarte Calderay Angel, Garcia Sierra Alberto, Garcia Suarez Victor Ignacio, Garcia Jose E., Lasheras Fernańdez Yolanda, Lazaro Rivera Mariano, Lazo Valverde Concepcion, Garcia Velasco Guillermo, Garcia Velasco Pilar, Naudin Victor, Leal Correa Bartolme, Lebrero Sańchez Encarnacioń, Garcıá Palacios Carmen, Garcıá Vilamea Jose´ Carlos, Garcia-Reyes Ledo Cabaleiro Jose´Marıá, Letona Antia Lurdes, Linãres Stolle Manuel, Ramos Mercedes, Gardoki Elorriaga Jose A., Garicano Lasa Critina, Lite Dıáz Annabel, Lizarribar Sans Marta, Llario Sanjuań Miguel, Llido J Am Soc Nephrol 17: S178–S188, 2006 Microalbuminuria in Hypertensive Patients with IFG S185

Vicedo Ricardo, Llinares Moreno Vicente, Lliteras Fleixas Gabriel, Castejoń Luis Alfredo, Miranda Ruiz Francisco, Modrego Navarro An- Llorens Edo Fernando, Llorente Martin Carmen, Lloscos Llavador Ger- gel, Molina Contreras Moises, Monfort Saez Rogelio, Monraba Capella man, Llull Sarralde Micaela, Lobato Delgado Luis Alberto, Lobato Miquel, Monsalve Terroń Manuel, Montagud Moncho Miguel, Mon- Fernańdez Manuel, Lobera Serrano Pedro, Loizaga Horno Juan, Lom- tan˜es Rustullet Carlos, Montero Luengo Juan, Montero Luque Javier, billo De Onãte Margarita, Lopez Abietar Ma Isabel, Lopez Abril Juan, Mora Breso´ Concha, Mora Dıáz Juan De Dios, Mora Garcia Cristina, Lopez Aisa Blanca, Lopez Andrino Juan Carlos, Lopez Bazo Pedro, Morales Abad Manuel A., Morales Colas Ma Luz, Moranco Sengariz Ma Lopez Cambeses Pilar, Lopez Cambeses Rosario, Lo´pez Castan˜eda A´ ngeles, Moreno De Mingo Javier, Moreno Gonzalez Antonia, Moreno Elvia, Lopez Castro Antonio Jose´, Lopez De Coca Fernandez-Valencia Marıń Germań, Moreno Minguez Vicente, Moreno Moreno Ana, Enrique, Lopez De La Calle Fernando, Lopez De La Fuente Elena, Moreno Moreno Jose Manuel, Moreno Beatriz, Moreno Esther, Moro Lopez Diaz Jesus, Lopez Hernandez Antonio, Lopez Leza Simon, Jimenez Juliań, Moro Torija Pilar, Moron Alejandre Angela, Morrell Lopez Lopez Francisco, Lopez Martinez Mario, Lopez Moreno Ma Del Rosario, Mosquera Martıńez Juan, Mourinõ Paz Amelia, Moya Cantar- Carmen, Lopez Munõz Felix, Lopez Rodriguez Isidro, Lopez Rodriguez ell Ma Victoria, Moya Santana Rafael, Mulet Sart Monserrat, Munar Jesus, Lopez Serrano Beatriz, Lopez Vazquez Luis Miguel, Lo´pez Cre- Mateu Juana Ana, Mun˜iz Fontainãs Manuel, Mun˜iz Villa Candelas, spo Yolanda, Lo´pez De La Fuente F. Javier, Lo´pez Galindo Pedro Luis, Munõz Conde Carmen, Munõz Hernańdez Jose´Gabriel, Munõz Mora Lo´pez Munõz Manuel, Lo´pez Ortiz Franciso, Lo´pez Ruiz Teresa, Lopez Francisco Javier, Munõz Rodriguez Pepe, Mur Martı´ Teresa, Muriel Perez Jose Manuel, Lopez-Cozar Fernandez Carmen, Lo´pez Carmen, Velasco Ana, Muruais Gonzalez Jesus, Napal Anaut Ma Olga, Naranjo Lorente Lopez Enrique, Lorente Mayor Juan, Lorenzo Lorenzo Jesus Carrioń Emilio Diego, Natal Gonza´lez Fernando, Navarro Martinez Francisco, Lorenzo Salido Francisco, Lozano Chilet Inmaculada, Lucas Victoria, Navarro Moreno Carlos, Navarro Soler Javier, Navarro Tarin Sańchez Roque, Lucero Avinã Jose´ Luis, Luengo Aguëro Jesus, Luis Ricardo, Navarro Tarin Vicente, Navarro Valero Diego, Navarro Vil- Ruiz Cristina, Luna Estevez Sergio, Luna Estevez Sergio, Luque Jime- lena Manuel, Navascues Beltran German, Navaz Tejeiro Julio, Navaza nez Miguel, Madero Ambrojo Emilio, Maduenõ Caro Antonio J., Mae- Dafonte Ana Maria, Nevado Munõz Rafael, Nicolau Pellicer Carmen, stre Amat Luis, Maestre Amat Luis, Maestro Castellblanque Esperanza, Niell Crespi Miguel, Nieto Hortal Pepe, Nogue´s Loboń Aurora, Novoa Maffiotte Carrillo Nicola´s, Mampel Almela Josep, Manzano Martinez Rodriguez Belen, Nuń˜ez Jorge Carlos, Ocanã Cazalilla Carmelo, Ogal- Antonio, Marchena Consejero Manuel, Marco Macian Ma Dolores, Mar- las Raya Fuensanta, Ojea Amoedo Enrique, Olea Carrasco Miriam, Olid cos Bailon Jesus, Marcos Fernandez Fco.Jose, Marcos Olea Javier Luis, Valle Antonio, Olina Iparragirre Anuska, Olivar Castrilloń Carmen, Marcos Rodriguez Angel, Margeli Ana, Mari Solivellas Bartolome, Olivares Escribano Quintin, Olivera Canãdas Guadalupe, Olivera Marin Castanõ David, Marıń Andre´s Fernando, Marıń Valero Jose´, Ramos Ana G., Olmos Diaz Francisco, Ontanõn Bort Juan Jose, Ordon˜ez Marque´s Calvo Inmaculada, Martel Martel Alberto, Martin Alfaro Picoń Roberto, Orgaz Gallego Pilar, Ormad Sebastian Javier, Orribo Maria Luisa, Martin Gomez Madel Carmen, Martin Martin Pedro, Rodrı´guez Severiana, Orrunõ Albizu Luis, Ortega De La Torre Llanos, Martin Sanchez Jose, Martıń Burillo Teresa, Martıń Garcıá Lourdes, Ortega Dıáz A´ ngel Felipe, Ortega Motilla Natividad, Ortega Rıós Fran- Martıń Garito Enrique, Martıń Martıńez Enrique, Martıń Millana Juan cisco Javier, Ortin Arronis Jose´Manuel, Ortiz Forcada Josefina, Ortueta Carlos, Martıń Moros Jose´Ma, Martıń Portal Alejandro, Martıń Serrano Ruiz De Arbulu Jesus, Otaduy Bengoa Santiago, Otero Arias Fernando, Fernando, Martıń Soledad Jose´ A, Martincano Jose Luis, Martinez Otero Cotoń Jose´, Otero Lopez Jose Manuel, Otxoa Iban˜ez Inãki, Oujo Andueza Camino, Martinez Ausin Ma Carmen, Martinez Barrios Jesus, Pujales Juan, Pablos Herrero Eva, Paches Porcar Ma Dolores, Padin Martinez Bes Ma Jose´, Martinez Cabrera Ana, Martinez Carrasco Jose Montoto Fernando, Padron Chao Antonio, Padroń Pe´rez Marcos, Pala- Luis, Martinez Castellanos Mar, Martinez Correcher Francisca, Mar- cio Monedero Carmen, Palacios Claramunt Juan Andres, Palacios Del tinez Eizagirre Jose Manuel, Martinez Fernandez Montserrat, Martinez Cerro Antonio, Palacios Gonzalez Eleazar, Pallare´s Hernańdez Maria Galvan Luis Alfonso, Martinez Garcia Candido, Martinez Garcia Pilar, Palma Lafuente Javier, Palomares Fernańdez Sixto, Palomo Del Eladio, Martinez Gonzalez Esteban, Martinez Gonza´lez Mercedes, Mar- Arco Jesu´s, Panero Juan Vicente, Pappalardo Ordinãna Eric, Pappa- tinez Hermosilla Alicia, Martinez Jativa Teresa, Martinez Lahuerta Juan lardo Ordinãna Eric, Pardo Diaz Beatriz, Paredes Martinez Ma Luz, Jose´, Martinez Linuesa Remedios, Martinez Martinez Jose Ma, Martinez Paredes Urraca Toma´s, Parra Rodriguez Francisco, Parralejo Cano Montero Juan Alberto, Martinez Nun˜ez Elisa, Martinez Orozco Marino, Francisco, Parrilla Rubio Margarita, Pascual Gil Octavio, Pascual Martinez Quess Dulce, Martinez Quilez Javier, Martinez Ramos Fco, Gonza´lez Oscar, Pascual Seara Benito, Pastor Benavent Carmen, Pastor Martinez Sanchez Luis, Martinez Vidal Angel, Martinez Vindel Juan Oliver Jose´Francisco, Pastor Pastor Juan, Pastrana Gonzalez Victoria, Carlos, Martıńez Guerola Carmen, Martıńez Pardo Inmaculada, Mar- Paya Perez JoseÁntonio, Payań Godoy Josefa, Pazos Lopez Jose´, Pe- tıńez Pardo Rafael, Martıńez Quintas Marıá Jose´, Martıńez Vazquez draz Garcıá Ma Isabel, Peiro Morant Juan, Pellit Ramil Jose Ignacio, Constantino, Martn Martin Araceli, Martorell Adsuara Vicente, Martos Penades Vaya Vicente, Pensado Pousa Jose´ Francisco, Penã Forcada Calzado Jose´, Martos Garcia Emilio, Mateo Cabrejas Jesu´s Javier, Ma- Carmen, Penãs Merino Antonio, Perales Bolado Javier, Peralta Mun- teos Mateos Jesu´s, Mateos Perez Mar, Matilla Alvarez Carmen, Maya guıá Lucıá, Pereira Aparicio Ma A´ ngeles, Perera Pe´rez Carmen G., Teresa, Mazquiarań Mendia Martıń, Medina Castanõ Antonio, Medina Perez Alemany Antonio, Perez Algar Ma Jose´, Perez Alonso Manuel, Cuenca Pedro, Medina Engler Berta, Medrano Gonzalez Maite, Megias Perez Bermudez Aurelio, Perez Domingo Elena, Perez Gallego Fran- Boils Araceli, Mejıás Gonza´lez Santiago, Mejuto Bernabe´Francisco J., cisco, Perez Garcia Catalina, Perez Llamas Miguel, Perez Perez Jose Mellizo Moya Angel, Mena Garcia Juan, Mena Sastre Francisco Javier, Luis, Perez Urraza Gotzone, Perez Vera Juan Antonio, Pe´rez Martıń Ma Mencıá De Castro Gaspar, Mencıá Herreras Jose´Ma, Mendez Gomez Del Puerto, Pe´rez Palmes M. Paz, Pe´rez Sańchez Jose´ Carlos, Pe´rez Begonã, Mendez Martinez Carmen, Mendez San Pedro Tomas, Mend- Vicente Antonio, Perez De Lis Fernandez Jesus, Perez De Olaguer ieta Ruiz Ma A´ ngeles, Mendiguren Navascues Arantxa, Mendinueta Clavell Juan Jose, Perez-Blanco Fernańdez Antonio, Perez-Romero Fernandez Carmen, Menedez Tamargo Jose Manuel, Meneńdez Martinez Jaime, Pericas Garcia Bartolome, Pericas Garcia Julio, Peris Piquero Manuel, Mengual Moll, Vicente, Merino Munõz Marta, Mesa Velarde Jose´Manuel, Peset Aleixandre Asuncioń, Picazo Moreno Edu- Pedrero Carlos, Mesquida Jerońima, Mestre Llugany Joan, Mialdea ardo, Pilar Claramonte Juan M, Pitarch Marco Florentina, Pla´ Vaya Lozano Maria Jose´, Milian Beser Susana, Minchero Arroyo Alberto, Rafael, Pleguezuelos Martinez Manuel, Ponce Buj Begonã, Poncela Minguez Villar Jose´ Carlos, Minguijon Barea Concha, Mininõ Couto Costas Elvira, Ponzola Sanchez Jose´ Manuel, Porcel Llado Miquel, Gerardo, Minuesa Cortijo Francisco Javier, Miquel Mira Ma Jose, Mira Porritt Lueiro Begonã, Portela Anton Jose, Porto Iglesias Jesus, Portus S186 Journal of the American Society of Nephrology J Am Soc Nephrol 17: S178–S188, 2006

Vinyeta Teresa, Pousa Estevez Lorenzo, Poveda Grau Vicente, Pozo Paz, Sebastian Milian Elena, Sedano Garcia Jose I., Segador Parra Jose, Teruel Amparo, Pradas Gonzalez Carmen, Pradela Leonardo Juan, Serrano Cumplido Adalberto, Serrano Guerra-Librero Javier, Serrano Prados Cano Dolores, Prados Del Pino Javier, Prats Villagrasa M° Jose, Mallagray Luis, Serrano Vaverde Leticia, Sidro Bou Luisa Fda, Sieiro Prieto Albino Luis, Prieto Carnicer Maria De Los A´ ngeles, Prieto Ferrer Prada Eudaldo, Siles Luna Maria Teresa, Siles Pozo Carmen, Simarro Nuria, Prieto Gonzalez Laureano, Prieto Seva Alvaro Jose´, Prieto Car- Rueda Marta, Sipan Sarrion Yolanda, Sirumal Hassamal Enrique, So- men, Prol Ranã Manuel, Puchalt Ana Maria, Pucholt Bergara Juan, brino Sorinas Eugenio, Soengas Vazquez Jose Antonio, Soler Carbo´ Puente Galań Oscar, Puente Martinez Antonio, Puente Perez Pablo, Montse, Soler David Vicente, Soler Lopez Tomas, Solera Albero Juan, Quevedo Rivera Julia, Quiles Anõn Fernando, Quindimil Vazquez Jose SOriano FUentes Segundo, Sorlı´ Guerola Jose´ Vicente, Sosa A´ lvarez Antonio, Quiros Alvarez Jesu´s, Raga Asins Martin, Raga Casasus Jose´ Cesar, Soto Figueiras Manuel, Soto Trigueros Juan De Dios, Suarez Vicente, Ralla Pablo Jordi, Rama Ferro Jesu´s, Ramia Mulet Jose Luis, Alen Jose´, Suarez Fernańdez Alejandro, Suarez Morań Ramoń, Sua´rez Ramirez Aparicio Antonio, Ramı´rez Perez Carlos, Ramos Aleixades Castro Nicanor, Suero Palancar Jose´, Tardıó Lo´pez Manuel, Tarrıó Adolfo, Ramos Hernańdez Santiago, Ramos Rodriguez Manuel, Ramos Tobar Manuel, Tejeda Serrano Ma Isabel, Tellado Rosello Jose L, Terron Rafael, Razoń Angulo Emilio, Real. Balaguer Vicente, Reboso Reyes Ruiz Maria Jesu´s, Testillano Perez Enrique, Thalamas Atienza Aitor, Cristina, Recio Ribote Lourdes, Reguillo Diaz Joaquina, Remoń Soriano Tienza Villalobos Marisa, Tirado Moliner Jose Ma, Toldos Villegas Agustina, Renteria Goirigolzarri Jon, Repiso Moreno Manuel, Requena Gregorio, Tolosana Almale Jose´Marıá, Tomas Marin Carolina, Tomas Solera Juan, Retis Vazquez Julio, Retuerta Garcıá Ma Dolores, Revert Pruneda Pedro, Torcal Potente Ana, Toribio Espino Espino J.Manuel, Algarra Adoracion, Revert Algarra Adoracioń, Rey Suarez Salvador, Tormo Quiles Facundo, Tormos Felip Amparo, Torre Expo´sito Juan Ribelles Cebrian Julio, Ribes Vicedo Juana, Ricart Cortes Jose Vicente, Simoń, Torrero Atienza Araceli, Torres Hernandez Candelaria, Torres Ridaura MartıÁmparo, Riera Calvo Andre´s, Rios Gomez Prados, Rios Vazquez Bernardo, Tranche Iparraguirre Salvador, Trujillo Pe´rez Isa- Rey Teresa, Ripoll Sanchez Jaime, Rivero Macristo, Robres Oliete Mari- bel, Turegano Albarran Miguel, Unanue Aurrekoetxea Juan Toma´s, ano, Roca Baeza Ramon, Roca Bosch Jose Luis, Roca Martinez Amparo, Unceta Aramburu Fernando, Urbe Castelruiz Patxi, Urdangarin Tolosa Roca VerduÁntonio A´ ngel, Roche Del Toro Marciela, Rodilla Alonso Elena, Uribeetxeberria Garcia Lourdes, Usoz Otal Ramon, Valero Bar- Angel, Rodriguez Bacardit Neus, Rodriguez Fernandez Benito, Rodri- celoĆarmen, Valero Valero Rosana, Valero Valero Rosana, Valhondo guez Fernandez Concepcion, Rodriguez Gallego Concepcion, Rodri- Elias Juan Antonio, Valle Garcia Nicanor, Valledor Puente Juan, Valle´s guez Garcia Amor, Rodriguez Ledo Pilar, Rodriguez Lopez Elisa, Ro- Romero Nuria, Valls Roca Francisco, Valverde Leis Jesus, Valverde driguez Lopez Isabel, Rodriguez Morua Javier, Rodriguez Ortiz De Lizundia Anton, Vaquer Perez Jose´ Vicente, Vara Gonza´lez Luis Al- Zarate Ma Luisa, Rodriguez Perez Jose Carlos, Rodriguez Quintela berto, Varela Rotger Cirıáco, Vargas Negrıń Francisco, Vargas Concha, a Jesus, Rodriguez Romo Antonio, Rodriguez Soriano Ma Jose, Rodriguez Vargas Rafael, Vazquez Garcia Manuel, Vazquez Ortega M Dolores, Tebar Fabiola, Rodriguez Vivar Antonio, Rodrı´guez Alvarez Jesu´s, Vazquez Ramos Elena, Velasco Escobar Pablo, Velasco Gemio Joaquin, Rodrı´guez BartolomeÉmilio, Rodrı´guez Franco Mercedes, Rodrı´guez Vendrell Torres Federico, Ventura Garcia Silvestre, Ventura Rodriguez Gallego Concepcioń, Rodrı´guez Pe´rez Ana Denis, Rodrı´guez Portillo Silvestre, Verdial Varela Jose Antonio, Vergara Ruiz Miguel, Vicente Fernando, Rodrı´guez Relucio Angela, Roig Valdivieso Monserrat, Rojo Diaz Juan Ignacio, Vicente Hernańdez Javier, Vicioso Pedro, Vidal Calderoń Aranzazu, Roldań Sanchez Pilar, Romero Conde Antonio, Mesa Claudio, Vidal Pardo Jose´, Vidal Planelles Francisca, Viejo Me- Romero Corroto Carmen, Romero De Lama Concepcion, Romero Gar- nendez Carmen, Vila Hernandez Luis, Vila Miro´ Ramon, Viladomiu a cia Cesar, Romero Mera Fernando, Ros Dominguez Jose, Rosell Pascual Montserrat, Vilaplana Bernabeu Carlos, Villa Pe´rez M Jesu´s, Cruchaga Luis, Rovira Penã Blanca, Rubert Escrig Carmina, Rubiera Villalobos Martı¨n Juan Carlos, Villanueva Gomez Isabel, Villanueva Alvarez Carlos, Rubio Arribas Victor, Rubio Beltran De Guevara Jesus, Horn Luis, Villanueva Zarate Juan Ramoń, Villar Guerrero Domingo, Rubio Fernandez Jose Fe´lix, Rubio Gonzalez Manuela, Rubio Guerrero Villaro´Gabarro´Merce`, Villasevil Hernandez Raul, Villora Fernandez Manuel, Rubio Ruiz Jose´Ma, Rubio Villar Montserrat, Rubio Teresa, Angel, Villoria Echegaray Juan Manuel, Villuela Gonza´lez Fernando, Ruiz Aguilar Gloria, Ruiz Chamorro Manuel, Ruiz Lopez Jesus, Ruiz Vilumbrales Llorente Roberto, Viota Esperanza, Viqueira Perez Ber- Pastor Luis, Ruiz Quintero Manuel, Ruiz Quintero Manuel, Ruiz Ramos nardo, Zanon Gonzalez Emilio, Zaragoza Moreno Ampara, Zardoya Rosa, Ruiz Roig Joaquina, Ruiz Ruiz Ana Marıá, Ruiz Vicente Juliań, Zardoya Milagros, and Zubiria Sopena Carlos. 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