microalbuminuria in type 2 diabetics: an important, overlooked cardiovascular risk factor

THE JOURNAL OF CLINICAL HYPERTENSION VOL. VI NO. III MARCH 2004134

The presence of microalbumin in the urine of persons with type 2 diabetes is perhaps the most important early signal heralding the onset of sys-temic vasculopathy and associated target organ damage to the brain, the heart, and the kidneys. It is easily measured and, unfortunately, frequent-ly overlooked as a screening tool in clinical medi-cine. If present, it identifies patients at risk for early cardiovascular death and progressive renal disease. Microalbuminuria also identifies patients who need more rigorous cardiovascular risk man-agement, especially more intensive blood pres-sure control, preferably below 130/80 mm Hg, and strict attention to glycemic control and lipid levels. Therapeutic strategies to facilitate better blood pressure control and reduce microalbumin-uria likely will prove to be the most effective way to retard not only the progression of renal disease but also cardiovascular disease. Consequently, the identification and normalization of urine microal-bumin excretion should be an important consider-ation in patients with diabetes. (J Clin Hypertens. 2004;6:134–143) ©2004 Le Jacq Communications, Inc.

Diabetes is not only the single most common cause of end-stage renal disease (ESRD) in the

Western world, but it is also a major risk factor for cardiovascular disease that often coexists in patients with high blood pressure.1,2 Third National Health and Nutrition Examination Survey (NHANES III) data indicate that diabetes affects 7.8% of adults over age 20 years in the United States and that the risk of developing type 2 diabetes is more than two times greater in patients with high blood pressure than in their normotensive counterparts.3 Moreover, 28.2% of patients with type 2 diabetes have micro-albuminuria, and 7.6% have clinical protein-uria.3 Without specific intervention, 20%–40% of patients with type 2 diabetes and microalbuminuria will progress to overt nephropathy and ultimately ESRD.2,3 Consequently, earlier screening techniques that identify patients at risk for progression of both renal disease and cardiovascular target organ dam-age are required. Screening for microalbuminuria may be one of the most important, simple clinical tools in practice.

MICROALBUMINURIA: A MARKER FOR CARDIOVASCULAR DISEASEIn type 2 diabetics, microalbuminuria is the earli-est clinical sign indicating vascular damage in the glomerulus, which is reflective of vascular disease throughout the body.4 Although only 20%–40% of type 2 diabetics with microalbuminuria prog-ress to overt nephropathy and ESRD,2,3 this figure would likely be much higher if these patients did not die from myocardial infarctions or strokes first. In other words, these patients do not live long enough to develop renal failure.

Epidemiologic evidence indicates that the presence of albuminuria is predictive of increased

R e v i e w P a p e r : C M E

Microalbuminuria in Type 2 Diabetics: An Important, Overlooked Cardiovascular Risk Factor

Matthew R. Weir, MD

From the Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD Address for correspondence: Matthew R. Weir, MD, Division of Nephrology, University of Maryland Hospital, 22 South Greene Street, N3 W143, Baltimore, MD 21201-1595 E-mail: [email protected] Manuscript received June 19, 2003; revised October 17, 2003; accepted October 22, 2003

www.lejacq.com ID: 2524

The Journal of Clinical Hypertension (ISSN 1524-6175) is published monthly by Le Jacq Communications, Inc., Three Parklands Drive, Darien, CT 06820-3652. Copyright ©2004 by Le Jacq Communications, Inc., All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at [email protected] or 203.656.1711 x106.

VOL. VI NO. III MARCH 2004 THE JOURNAL OF CLINICAL HYPERTENSION 135

cardiovascular morbidity and mortality indepen-dent of other cardiovascular risk factors.4 There is a near linear relationship between increasing urinary protein excretion and both myocardial infarction and stroke in patients with type 2 diabe-tes.5–8 These observations are also valid in patients without type 2 diabetes.9,10 Thus, screening for albumin, or protein in the urine, (even with lower levels below 150 mg/d) can have important predic-tive value for identifying patients who are more likely to experience a cardiovascular event.

Gerstein and colleagues8 analyzed information from the Heart Outcomes Prevention Evaluation (HOPE) study and noted that microalbuminuria was a powerful predictor for major cardiovascular events (myocardial infarction, stroke, or cardiovas-cular death) and all-cause mortality in patients with and without diabetes. Of the more than 9000 high-risk patients who were screened for this study, an abnormal baseline urine albumin to creatinine ratio measurement was detected in 33% of patients with diabetes and in 15% of patients without diabetes. A linear graded relationship was observed between the urine albumin to creatinine ratio and cardiovascular morbidity and mortality. The large number of study participants allowed the investigators to note that the graded relationship between albumin to creati-nine ratio and cardiovascular mortality was evident well below the standard microalbuminuria thresh-old (30 mg/g creatinine), indicating that screening should occur early so preemptive cardiovascular risk reduction therapy can be planned (Figure 1).

Microalbuminuria is also commonly associated with cardiovascular risk clustering phenomena.11 This has been most commonly called the metabolic

cardiovascular syndrome and indicates the associa-tion between high blood pressure, left ventricular hypertrophy, central obesity, microalbuminuria, dyslipidemia, glucose intolerance, and loss of nocturnal dip of blood pressure.11 Consequently, the interplay of these risk factors leading to blood vessel damage may be best determined by the early appearance of microalbumin in the urine. Hence, a simple, clinical measurement of urine albumin is useful for not only identifying cardiovascular risk clustering phenomena, but also for identifying increased risk for cardiovascular events.

MICROALBUMINURIA: A MARKER OF RENAL INJURYThe presence of microalbumin in the urine heralds the onset of kidney disease in diabetics.4,12–14 It is not known whether it indicates greater risk for kidney disease in patients without diabetes. The presence of albumin indicates early damage to the glomerular blood vessels; however, in diabetics it also could indi-cate failure of renal autoregulation. Although there is no direct clinical evidence to support this theory, microalbuminuria is evidence of generalized impair-ment of vascular function,15 and one of the critical responsibilities of the afferent glomerular arteriole is to assist in the regulation of glomerular hemodynam-ics.16 This may be an important concern in patients with diabetes. Consequently, improved control of glomerular capillary pressure with better systemic blood pressure control with drugs that block the renin-angiotensin system have increasing importance to avoid progressive renal injury.

Renal autoregulation is the physiologic mecha-nism whereby glomerular capillary pressure is exquisitely controlled within about 5 mm Hg despite a wide range of renal perfusion pres-sures.17,18 The afferent and efferent glomerular arterioles serve as the resistors of blood flow pass-ing through glomerulus. Alterations in vascular tone of the afferent and efferent arteriole regu-lates intraglomerular pressures. Increasing systemic blood pressure should elicit a myogenic response at the afferent glomerular arteriole to initiate reflex contraction that reduces renal blood flow to a level that is appropriate for filtration (mean arterial pressure 70–80 mm Hg).17,18 During situa-tions of diminished effective arterial blood volume, the efferent glomerular arteriole vasoconstricts to restore necessary filtration pressure within the glomerulus to maintain ultrafiltration.19 An addi-tional mechanism that facilitates preglomerular vasoconstriction is the increased delivery of sodium chloride to the distal nephron, which stimulates

Figure 1. The relationship between cardiovascular events (%) and urine albumin to creatinine ratio in patients from the Heart Outcomes Prevention Evaluation (HOPE) study. Note the continuous relationship, even below the microalbuminuria threshold (30 mg/g cre-atine)8; deciles 1 and 2 are combined because of very low incidence rates in these two deciles Adapted with permission from JAMA. 2001;2865:421–426.8



a tubular glomerular feedback mechanism.20 In healthy persons, these autoregulatory systems oper-ate quite effectively despite a wide range of perfu-sion pressures17–19; however, in patients who have diabetes, there is early development of vascular disease. When this occurs at the afferent arteriole, renal autoregulation of blood flow is impaired. Consequently, systemic pressures are more easily transmitted to the glomerular capillary, which can lead to injury. For example, even if the patient has a “normal” systemic blood pressure of 130 mm Hg, if inadequate afferent glomerular vasoconstric-tion occurs, this systemic pressure could be only partially dampened as it enters the glomerulus and could lead to progressive mechanical injury.

The relationship between albuminuria and pro-gressive renal injury is not completely understood. On one hand, the albuminuria could be indicative of elevated glomerular capillary pressures that over time could lead to mechanical stretch and strain and resultant vascular injury of the filtering apparatus.21 On the other hand, there is experimental evidence to indicate that renal epithelial cell uptake of filtered proteins may lead to an abnormal accumulation of proteins in the endolysosomes and endoplasmic reticulum that could stimulate nuclear signals for vasoactive and inflammatory genes.22 The subse-quent release of these vasoactive and inflammatory substances within the renal interstitium could lead to myofibroblast proliferation, fibrogenesis, and subsequent scarring.22 The presence of glomeru-lar capillary hypertension, albuminuria, and renal tubular epithelial cell reabsorption of filtered pro-teins may be the necessary combination of events to serve as a final common pathway for progressive renal injury. These observations also raise questions about optimal strategies to protect kidney function and whether specific antimicroalbuminuric or anti-proteinuric regimens are as important as, or more important than, other cardiovascular risk reduction strategies, such as lowering blood pressure or lipids, in preventing progression of renal disease.

SCREENING FOR MICROALBUMINURIAMicroalbuminuria can be defined by different mea-surements as shown in Table I. There are three meth-ods for screening for microalbuminuria: measure-ment of spot urinary albumin to creatinine ratio, 24-hour urine collection with albumin and creatinine, and a timed 8-hour or overnight urine collection to measure the albumin to creatinine ratio.

The spot determination is the easiest to use in an office setting and often provides accurate information. It has been demonstrated to be at least 90% sensitive

for determining microalbuminuria compared with a 24-hour urine collection, even after adjusting for age and gender.23–26 It is best performed with first morn-ing void urine because of the known diurnal variation in albumin excretion.27 One can rely on the uniformi-ty of timing with repetitive specimens. If urine collec-tions are used, the ratio of the albumin (in milligrams) to creatinine (in grams) should be measured, as the timed collection of urine specimens is often difficult to perform accurately. Because urine creatinine produc-tion is constant on a daily basis (it reflects the muscle mass and its breakdown products) the only variability is the urine albumin excretion. This obviates the need for a timed specimen and encourages the use of spot specimens for screening. The spot specimen can also serve as a means for determining response to antimi-croalbuminuric therapy. The simplicity of the mea-surement allows for its use for monitoring purposes.

Because of the variability in urinary albumin excretion, two or three specimens collected within a 3- to 6-month period should be abnormal before considering the patient to have crossed one of the diagnostic thresholds of albuminuria.2 As discussed previously, there is a continuum of risk based on increasing albumin in the urine even below the tra-ditionally reported thresholds, as outlined in Table I. Note that normal is defined as <30 mg/g creati-nine. Microalbuminuria is 30–299 mg/g creatinine, and overt nephropathy or clinical albuminuria is

Table I. Diagnostic Criteria for AlbuminuriaSPOT

SPECIMEN(NOT TIMED)

SPOT SPECIMEN

(NOT TIMED)

24-HOUR SPECIMEN(TIMED)

Normo albuminuria

>300 mg/g cr <20 mg/mL <30 mg/g cr

Micro albuminuria

30–299 mg/g cr

20–200 mg/dL

20–299 mg

Micro albuminuria

>300 mg/g cr >200 mg/mL

≥300 mg

cr=creatinine

Table II. Benefits of Renin-Angiotensin-Aldosterone System Blockade for Renal ProtectionHemodynamic effects

Reduction in systemic blood pressureReduction in glomerular capillary pressurePossible reduction in proteinuria

Nonhemodynamic effectsPossible stimulation of extracellular matrix degradationPossible inhibition of macrophage/monocyte infiltration Possible reduction of oxidative stress



≥300 mg/g creatinine.2 One can also use 24-hour collections in milligrams per 24 hours or timed col-lections in micrograms per minute. However, for simplicity, spot collections evaluating milligrams of albumin per grams of creatinine should be used as the standard. Also, please note that some of the variability in urinary albumin excretion can be based on exercise, infection, or fever within the previous 24 hours. In addition, poor glycemic con-trol, marked hypertension, congestive heart failure, urinary tract infection, protein and salt intake, and even hematuria may elevate urinary albumin excre-tion over baseline.2

Screening should always be performed by mea-suring microalbuminuria, not by measuring protein. Protein measurements in the urine are not sensitive at lower determination levels and are consequently unreliable.28 Screenings with reagent tablets or dipsticks may also be used since they show accept-able sensitivity and specificity when carried out by trained personnel. However, the reagent strips only indicate concentration and do not correct for cre-atinine as the spot urine albumin to creatinine ratio does. Thus, there is greater potential for errors in quantification of albumin in the urine based on variations in urine concentration. Any positive test by a reagent strip or tablet should be confirmed by a more specific spot urine albumin to creatinine ratio for quantitation purposes.

RATIONALE FOR REDUCING MICROALBUMINURIA OR PROTEINURIAThe rationale for reducing microalbuminuria or proteinuria is based on the clinical evidence linking proteinuria to not only cardiovascular events but also to progressive loss of renal function.12–14,29–35 The severity of albuminuria or proteinuria par-allels renal disease progression. This has been demonstrated in patients both with and without diabetes.30,36 Consequently, antihypertensive and antiproteinuric renal protective strategies are of great interest. The key clinical questions are: How low should we reduce blood pressure in the proteinuric patient? and, specifically, What drugs should we use? If glomerular autoregulation is impaired, mean systemic blood pressure should be reduced to near ideal glomerular capillary pressure levels of 70–80 mm Hg; however, this is often a blood pressure that may induce presyncope and is not necessarily clinically practical. There is likely a continuum of benefit associated with lower systolic pressures (below the currently recommended 130 mm Hg systolic) and reduction of risk of progres-sion of renal disease that can be measured as a

graded reduction in albumin or protein excretion. This may be analogous to the relationship between urine albumin excretion and cardiovascular events observed in the HOPE study.8

Antihypertensive agents that target the renin-angiotensin system, such as the angiotensin-con-verting enzyme (ACE) inhibitor or the angiotensin II receptor blocker, have been demonstrated to have more potent antiproteinuric effects with similar degrees of blood pressure reduction compared with other antihypertensive drug classes.30,37–44 The majority of these clinical trials demonstrate that opportunity for reducing proteinuria reduces the rate of progression of renal disease.30,37–44 Is this an effect of the drug on reducing blood pressure, reducing proteinuria, both, or on other factors not yet fully understood (Table II)? The answer is prob-ably all of these. The simultaneous reduction of both systemic blood pressure and glomerular capil-lary blood pressure is likely the most important and may explain some of the decrease in proteinuria and lessened glomerular injury through a reduction in mechanical stretch and strain.22,39 However, drugs that block the renin-angiotensin system also disrupt other profibrogenic and scarring pathways that may be important in protecting against glomerular scarring as well as tubulointerstitial injury.22,45

The benefits of renin-angiotensin blockade were first noted with the ACE inhibitors in experimen-tal models.21 Subsequently, clinical studies in type 1 and type 2 diabetics41,43,44 demonstrated an important advantage for these drugs in preventing doubling of serum creatinine and ESRD. Viberti et al.37 studied 92 patients with type 1 and type 2 diabetes and persistent microalbuminuria who had a mean blood pressure of 124/77 mm Hg and nor-mal renal function. Patients were randomized to receive either the ACE inhibitor captopril or a pla-cebo. After 2 years of treatment, the mean blood pressure in the captopril group was 122/74 mm Hg compared with 126/76 mm Hg in the placebo group. This 4/2 mm Hg difference was statisti-cally different and could explain why the captopril group had a 50% reduction in progression from microalbuminuria to clinical proteinuria.

Ravid et al.38 studied enalapril 10 mg vs. placebo therapy in 156 patients with type 2 diabetes who had a mean blood pressure of 130/80 mm Hg and urine albumin excretion rate of about 30 mg/24 hours. After 5 years of follow-up, ACE inhibitor therapy effectively suppressed an increase in micro-albuminuria, whereas those on placebo progressed to develop more clinical proteinuria. Mean arterial pressures increased from 96.1 to 102 mm Hg in



the patients receiving placebo, whereas they only increased slightly, from 98.2 to 100 mm Hg, in patients receiving the ACE inhibitor. Thus, these two studies demonstrate the importance of using ACE inhibitor therapy early in microalbuminuric patients who do not manifest the traditional defini-tion of high blood pressure or renal insufficiency. However, these studies cannot answer the question of whether this was a unique effect of the drug or a blood pressure effect.

The Collaborative Study Group41 answered this question in type 1 diabetics when they reported their data on 409 patients with type 1 diabetes who had urinary protein excretion rates over 500 mg/d and serum creatinine levels of >2.5 mg/dL who were randomized to receive either an ACE inhibitor or placebo plus other medicines to con-trol blood pressure below 140/90 mm Hg. After more than 4 years on study therapy, patients in the ACE inhibitor arm had a slower decline in renal function and displayed a 50% reduction in the risk of death, dialysis, and transplantation41 despite no substantial differences in the net blood pressure achieved in the two groups. These results cemented the ACE inhibitor as an important therapeutic strategy in type 1 diabetic hypertensives.

Despite the important observations of this land-mark study, there was little convincing evidence about strategies for reducing microalbuminuria and proteinuria with regard to clinical outcome in type 2 diabetics until three important studies were simul-taneously published in the New England Journal of Medicine in September 2001.42–44 These three stud-ies provided important new understandings about the relationship of pharmacotherapy (all three stud-ies used an angiotensin II receptor blocker), level of blood pressure control, and change in albuminuria or proteinuria with renal outcomes.

The Irbesartan Microalbuminuria in Type 2 Diabetics (IRMA-2) trial42 evaluated the impact of three different antihypertensive regimens on the rate of progression of microalbuminuria to clinical proteinuria in patients with hypertension, type 2 diabetes, and normal renal function. Patients could be randomized to receive placebo, irbesartan 150 mg, or irbesartan 300 mg plus additional conven-tional antihypertensive drugs to lower blood pres-sure below 140/90 mm Hg. They were followed for 2 years. Despite nearly identical reductions in blood pressure in all three groups, approximately 153/90 mm Hg to 140/83 mm Hg, there was a substantial reduction in risk for patients developing overt pro-teinuria if their antihypertensive regimen contained irbesartan 150 mm Hg (relative risk reduction,

39%; p=0.08) or irbesartan 300 mg (relative risk reduction, 70%; p≤0.001) (Figure 2). The results of this study indicate that including a higher dose of an angiotensin II receptor blocker, independent of changes in blood pressure, helped reduce the risk for progression of microalbuminuria to clini-cal proteinuria. What was sobering in this study was that nearly 15% of patients progressed from microalbuminuria to clinical proteinuria in 2 years without an angiotensin II receptor blocker as part of the antihypertensive regimen despite reducing blood pressure to 140/90 mm Hg. With irbesartan 300 mg, this risk was reduced to about 5%.

The Reduction in Renal Endpoints in Type 2 Diabetes with Angiotensin II Antagonist Losartan (RENAAL)43 and Irbesartan Diabetic Nephropathy Trials (IDNT)44 trials were performed in type 2 diabetics with hypertension, early renal insufficien-cy, and clinical proteinuria. Angiotensin II receptor blockade with either losartan 100 mg or irbesartan 300 mg, respectively, was a more effective strategy in preventing the composite end point of doubling of serum creatinine, reaching ESRD, or death com-pared with a traditional diuretic/β blocker or cal-cium channel blocker-based approach (p=0.02). In both of these studies, having an angiotensin II recep-tor blocker as part of a multidrug antihypertensive regimen consistently provided a more effective antiproteinuric effect compared with a traditional or calcium channel blocker-based approach. In the RENAAL trial, the level of achieved proteinuria reduction was predictive of renal and cardiovascu-lar events (unpublished observations). In the IDNT

Figure 2. The effect of placebo or irbesartan 150 mg or irbesartan 300 mg plus conventional antihypertensive therapy for 2 years on the risk for developing clinical proteinuria (>300 mg/d) in 590 patients with hyperten-sion, type 2 diabetes, and microalbuminuria Adapted from N Engl J Med. 2001;345:870–878.42



trial, not only did baseline 24-hour urine protein predict outcome with a doubling of risk for every doubling of protein, the study also demonstrated 50% reduction of proteinuria at 12 months was associated with a 50% reduction in the risk for doubling of serum creatinine or reaching ESRD.36 The results of these two studies demonstrate that it is not how much proteinuria you start with, it is how much you finish with that is predictive of your risk for developing renal insufficiency.

These studies provide important insight into the use of renin-angiotensin system blockers in type 2 diabetics for not only reducing blood pressure but also reducing proteinuria and slowing the risk for progression of microalbuminuria to clinical pro-teinuria, as well clinical proteinuria to doubling of serum creatinine or ESRD. However, no studies have been designed to correlate the antiproteinuric effect with the renoprotective effect.

Other antihypertensive medications are capable of reducing microalbuminuria/proteinuria beyond what would be expected by their antihypertensive effects. Perhaps the most useful are the nondihy-dropyridine calcium antagonists.46–48 These drugs, either alone or in combination with other drugs like ACE inhibitors, help lower both blood pres-sure and microalbuminuria/proteinuria.49 Most of the clinical trials were performed in patients with clinical proteinuria. There has been some concern that dihydropyridine calcium antagonists may increase or not change proteinuria in patients when used without a renin-angiotensin-system-blocking drug.46–48 However, when used with ACE inhibitors or angiotensin II receptor block-ers, this is not a concern.50,51

IMPLICATIONS FOR CLINICAL PRACTICEEarlier identification and management of patients with microalbuminuria or clinical proteinuria is imperative. Microalbuminuria is a much more easily treatable clinical problem than proteinuria in that the blood pressure tends to be lower, renal function is usually less impaired, and less medica-tion to reduce albuminuria is required.

ACE inhibitors and angiotensin II receptor block-ers have been convincingly demonstrated to have renoprotective benefits.30,41–44 The majority of the data with the ACE inhibitor is in type 1 diabetics and in patients with nondiabetic renal disease.30,41 The more recent data with angiotensin II receptor block-ers is confined to patients with type 2 diabetes42–44; however, more often than not these patients will require multiple drugs to achieve the lower levels of blood pressure, which may be important in correct-

ing glomerular capillary hypertension and optimally reducing proteinuria. Newer strategies to use com-binations of drugs will likely prove to be important. Early studies indicate that using an ACE inhibitor and an angiotensin II receptor blocker together may be better than using either one alone in the approved dosing range to reduce microalbuminuria or pro-teinuria.52,53 The addition of a thiazide diuretic or a nondihydropyridine calcium antagonist may also amplify the antiproteinuric effects of drugs that block the renin-angiotensin system.49,54 Moreover, most of the renal outcome trials with ACE inhibitors or angiotensin II receptor blockers included diuretic support and/or calcium antagonists to achieve better blood pressure control.

More studies are also needed to evaluate higher doses of ACE inhibitors and angiotensin II receptor blockers beyond those which have been shown to be useful for high blood pressure, to see whether better antiproteinuric effects and enhanced renal protection can be achieved. Additionally, clinicians need to be aware that modification of dietary salt consumption is crucial to optimize the antiprotein-uric effects of both ACE inhibitors and angiotensin II receptor blockers55 because increasing dietary sodium will offset both the antihypertensive and antiproteinuric effects of these drugs.

CONCLUSIONSScreening for microalbuminuria should be per-formed on a yearly basis in every patient with type 2 diabetes, as recommended by the American Diabetes Association.2 The presence of microalbuminuria indicates that a patient is at greater cardiovascular risk and consequently will require lower blood pres-sure goals (less than 130/80 mm Hg) and more spe-cific attention to lipids, glucose, diet, and platelets, as well as antimicroalbuminuric therapies.

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44 Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–860.

45 Weir MR, Dzau VJ. The renin-angiotensin-aldosterone system: a specific target for hypertension management. Am J Hypertens. 1999;12:205S–213S.

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INSTRUCTIONS FOR COMPLETING THIS FORM: Read the selected paper and answer all the questions that follow. After each question there is a series of possibly correct answers. Please select the one best answer for each and place your selection on the answer grid. YOU MUST ALSO COMPLETE THE CME EVALUATION SECTION and return the form within 6 months of the paper’s publication to receive credit. Letters of credit will be mailed to participants biannually.

ACCREDITATION STATEMENT: Winthrop-University Hospital (WUH) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. WUH designates this Continuing Medical Education activity for a maximum of (1) credit hour in Category 1 credit towards the AMA Physicians’ Recognition Award. Each physi-cian should claim only those hours of credit that he/she actually spent on the educational activity. WUH relies upon faculty participants in its CME programs to provide educational information that is objective and as free of bias as possible. In this spirit, and in accordance with the guidelines of the program sponsor, faculty participants are expected to indicate any commercial relationship that might be per-ceived as a real or apparent conflict of interest.

OBJECTIVE AND TARGET AUDIENCE: All primary care physicians and cardiologists are eligible to receive credit. At the conclusion of this activity, participants should be able to: 1) summarize the important points discussed in the paper reviewed; 2) identify patients to whom the paper is relevant; 3) modify management practices as new information is learned; and 4) identify deficiencies in their knowledge base.

1. Microalbumin in the urine of a patient with type 2 diabetes mellitus is:A __Screened for routinelyB __An indication that blood pressure in

well controlledC __An indication of good glucose controlD __A heralding sign of systemic vasculopathy

2. The percentage of patients with type 2 diabe-tes mellitus with microalbuminuria who will develop nephropathies is:A __20%–40%B __10%–20%C __10%–15%D __5%–10%

3. The statistic referred to in Question 2 would be higher if these patients:A __Were routinely screened for microalbuminB __Had other risk factors for renal failureC __Did not succumb to myocardial infarc-

tions or strokes firstD __Were normotensive

4. The Heart Outcomes and Prevention Evaluation (HOPE) study results support the idea that:A __Microalbuminuria is not a powerful pre-

dictor of cardiovascular riskB __Screening for microalbumin should occur

early to preempt cardiovascular riskC __Persons without diabetes need to follow

the same screening processD __ Increased microalbumin level is not associ-

ated with increased mortality

5. Cardiovascular risk clustering phenomena include all of the following except:A __ObesityB __HypertensionC __Glucose intoleranceD __Right ventricular hypertrophy

CME QuestionsTodd C. Kerwin, MD, Section Editor, Winthrop-University Hospital, Division of Cardiology, Winthrop Cardiology Associates, Mineola, NY

Please Select the One Best Answer for Each and Place Your Selection on the Answer Grid.

CME Answers are available from The Journal of Clinical Hypertension page at www.lejacq.com



Answer the questions from the previous page by selecting the best choice of A, B, C, or D

Questions: 1.__ 2.__ 3.__ 4.__ 5.__

Agree Disagree

1. My knowledge was enhanced by this activity. 1.__ 2.__ 3.__ 4.__ 5.__

2. The activity helped to clarify issues specific to hypertensive patients. 1.__ 2.__ 3.__ 4.__ 5.__

3. The information obtained from this exercise will have an impact on my care of patients. 1.__ 2.__ 3.__ 4.__ 5.__

4. The format of the exercise was useful. 1.__ 2.__ 3.__ 4.__ 5.__

5. Suggestions for future topics:

CME Answer Grid

CME Evaluation

Please print all information. Please submit a $5.00 administrative fee in the form of a check

made out to the Office of Academic Affairs-WUH.

SEND TO:Office of Academic AffairsWinthrop-University Hospital259 First StreetMineola, NY 11501

Re: Weir MR. Microalbuminuria in type 2 diabetics: an important, overlooked cardiovascular risk factor. J Clin Hypertens (Greenwich). 2004;6:134–143.

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Where to Send the Completed CME Form


VOL. VI NO. V MAY 2004 THE JOURNAL OF CLINICAL HYPERTENSION 241

E r r a t u m

J Clin Hypertens (Greenwich). 2004;6:146. Should Hypertensive Patients Take Aspirin? A Report From the Food and Drug Administration Thomas G. Pickering, MD, DPhil

In the heading, the section editor was incorrectly reported. It should have appeared as follows:

Reflections in HypertensionThomas G. Pickering, MD, DPhil, Associate Editor in Chief


microalbuminuria in type 2 diabetics: an important, overlooked cardiovascular risk factor

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