Microalbuminuria in treated hypertensives: only a mirror image of cardiovascular risk? The HUNT Study, Norway.

OBJECTIVES: Microalbuminuria as an independent marker of cardiovascular morbidity and mortality in hypertensive individuals is under debate. The aim of this study was to study the possible associations between microalbuminuria on one hand and known cardiovascular risk factors and cardiovascular disease on the other hand, in a large, unselected population of treated hypertensives without diabetes. DESIGN: Cross-sectional study. SETTING: Participants of the HUNT Study, Norway (n = 65,258). SUBJECTS: 5,369 individuals (> or =20 years) with treated hypertension delivered three morning urine samples for microalbuminuria analysis. MAIN OUTCOME MEASURES: Microalbuminuria expressed as albumin-to-creatinine ratio, cardiovascular risk factors and cardiovascular disease. RESULTS: Increasing age, pulse pressure (systolic blood pressure-diastolic blood pressure), s-creatinine, cigarette pack years, cardiovascular disease, antihypertensive medication group, and years with antihypertensive medication were significantly associated with microalbuminuria in men. Increasing pulse pressure, cigarette pack years, and antihypertensive medication group were associated with microalbuminuria in women, adjusted for other cardiovascular risk factors. When excluding individuals of both sexes with self-reported cardiovascular disease and blood pressure > 160/90 mm Hg, no variable associated with cardiovascular risk factors registered was statistically associated with microalbuminuria. CONCLUSION: The present study indicates that microalbuminuria mainly represents a mirror image of hypertension (BP > 160/90) and prior or present cardiovascular disease. We therefore question whether the treatment quality would improve if yet another risk factor, microalbuminuria, were introduced as a routine test in treated hypertensives.

International comparison of the relationship of chronic kidney disease prevalence and ESRD risk.

ESRD incidence is much lower in Europe compared with the United States. This study investigated whether this reflects a difference in the prevalence of earlier stages of chronic kidney disease (CKD) or other mechanisms. CKD prevalence in Norway was estimated from the population-based Health Survey of Nord-Trondelag County (HUNT II), which included 65,181 adults in 1995 through 1997 (participation rate 70.4%). Data were analyzed using the same methods as two US National Health and Nutrition Examination Surveys in 1988 through 1994 (n = 15,488) and 1999 through 2000 (n = 4101). The primary analysis used gender-specific cutoffs in estimating persistent albuminuria for CKD stages 1 and 2. ESRD rates and other relevant data were extracted from national registries. Total CKD prevalence in Norway was 10.2% (SE 0.5): CKD stage 1 (GFR >90 ml/min per 1.73 m2 and albuminuria), 2.7% (SE 0.3); stage 2 (GFR 60 to 89 ml/min per 1.73 m2 and albuminuria), 3.2% (SE 0.4); stage 3 (GFR 30 to 59 ml/min per 1.73 m2), 4.2% (SE 0.1); and stage 4 (GFR 15 to 29 ml/min per 1.73 m2), 0.2% (SE 0.01). This closely approximates reported US CKD prevalence (11.0% in 1988 through 1994 and 11.7% in 1999 through 2000). The relative risk for progression from CKD stages 3 or 4 to ESRD in US white patients compared with Norwegian patients was 2.5. This was only modestly modified by adjustment for age, gender, and diabetes. Age and GFR at start of dialysis were similar, hypertension and cardiovascular mortality in the populations were comparable, but US white patients were referred later to a nephrologist and had higher prevalence of obesity and diabetes. In conclusion, CKD prevalence in Norway was similar to that in the United States, suggesting that lower progression to ESRD rather than a smaller pool of individuals at risk accounts for the lower incidence of ESRD in Norway.

Microalbuminuria and all-cause mortality in treated hypertensive individuals: does sex matter? The Nord-Trøndelag Health Study (HUNT), Norway.

BACKGROUND: In hypertensive individuals, few prospective studies are available in which the association between microalbuminuria (MA) and all-cause mortality in the 2 sexes have been studied within the same population. METHODS AND RESULTS: We conducted a 4.3-year follow-up of 2307 men and 3062 women (> or =20 years old) with self-reported treated hypertension, all identified in the Nord-Trøndelag Health Study (HUNT), Norway, 1995 to 1997 (n=65 258). The main outcome measures were relative risk (RR) of all-cause mortality according to increasing albuminuria, defined at different levels of albumin-to-creatinine ratio (ACR). There was a consistent positive association between increasing ACR and all-cause mortality in men. The adjusted RR for ACR in the fourth quartile (> or =1.70 mg/mmol) was 1.6 (95% CI, 1.0 to 2.6), compared with ACR in the first quartile (<0.55 mg/mmol). The corresponding RR in women was 1.5 (95% CI, 0.8 to 3.1). We found a positive association between mortality and increasing number of urine samples with ACR above different cutoff levels, especially in men. In 3 urine samples, the lowest ACR level associated with mortality in men was 0.86 mg/mmol, RR 1.6 (95% CI, 1.1 to 2.4). The sex differences persisted after exclusion of those who died during the first year of follow-up, those with hypertension not treated optimally, and those with known cardiovascular disease. CONCLUSIONS: The association between ACR and all-cause mortality was stronger in treated hypertensive men than in women. The persistent sex differences indicate that hypertensive women tolerate MA better than men and that MA in women should be interpreted differently than in men.

Microalbuminuria and all-cause mortality in 2,089 apparently healthy individuals: a 4.4-year follow-up study. The Nord-Trøndelag Health Study (HUNT), Norway.

BACKGROUND: To date, there are few large follow-up studies of apparently healthy subjects with microalbuminuria (MA). The aim of this study is to examine the association between MA and all-cause mortality in nondiabetic nonhypertensive individuals. METHODS: We conducted a 4.4-year mortality follow-up of 2,089 men and women (> or =20 years) without diabetes and treated hypertension, randomly selected from the population-based Nord-Trøndelag Health Study (1995 to 1997; n = 65,258). Main outcome measures were adjusted relative risk (RR) for all-cause mortality according to increasing albuminuria, defined at different albumin-creatinine ratio (ACR) levels and in 1/2 or 3 urine samples. The main analysis was performed after exclusion of those with cardiovascular disease. RESULTS: There was a positive association between all-cause mortality and MA. The lowest ACR level associated with increased RR for mortality was the 60th percentile (> or =6.7 microg/mg [0.76 mg/mmol]; RR, 2.4; 95% confidence interval, 1.1 to 5.2), applying 3 urine samples with an ACR greater than the cutoff level. We found a positive association between mortality and increasing numbers of urine samples with an ACR greater than different cutoff levels, in which 3 urine samples were superior. Results persisted after adjusting for several confounders and excluding individuals with untreated hypertension (systolic blood pressure > or = 140 mm Hg/diastolic blood pressure > or = 90 mm Hg) and those who died during the first year of follow-up. CONCLUSION: Although this study confirms the association of all-cause mortality and ACR level in apparently healthy individuals, intervention trials are necessary before clinical cutoff levels of ACR are established and before screening programs are recommended.

Microalbuminuria in diabetic and hypertensive patients and the general population--consequences of various diagnostic criteria--the Nord-Trøndelag Health Study (HUNT).

OBJECTIVE: The purpose of this paper was to study the prevalence of microalbuminuria (MA) in males and females of various ages by applying various diagnostic criteria. Three groups of subjects were studied: apparently healthy individuals; self-reported hypertensives; and diabetics. MATERIAL AND METHODS: A total of 9255 individuals (age > or =20 years), all of whom were identified from the large (n = 65 258) population-based Nord-Trøndelag Health Study (HUNT) performed in Norway between 1995 and 1997, delivered three morning urine samples for MA analysis. Of these individuals, 651 reported both diabetes and treated hypertension, 944 diabetes only and 5547 treated hypertension only. The remaining 2113 subjects without diabetes or treated hypertension were randomly selected. The albumin:creatinine ratio (ACR) was used as an expression of urine albumin excretion. RESULTS: Applying the classical definition of MA of ACR > or =2.5 mg/mmol in at least two out of three urine samples, the prevalence of MA in those with both diabetes and hypertension was 42.2% in males and 25.9% in females; corresponding values for those with diabetes only were 27.8% and 22.4%, for the hypertensives 19.3% and 11.5% and for the randomly selected sample 5.2% and 4.7%. The prevalence of MA increased strongly with increasing age for both genders in all subgroups. The prevalence of MA changed considerably when applying different cut-off values of ACR and at least one, two or three urine samples with ACRs above the cut-off value. CONCLUSIONS: This study, one of the largest cross-sectional screening studies of MA ever performed, clearly illustrates the consequences of applying different diagnostic criteria. The optimal cut-off levels of MA for the prediction of cardiovascular disease still remain to be properly defined, and more follow-up studies are therefore needed.