Hypertensive women with the metabolic syndrome are at risk ... - Nature

Journal of Human Hypertension (2009) 23, 97–104 & 2009 Macmillan Publishers Limited All rights reserved 0950-9240/09 $32.00 www.nature.com/jhh

ORIGINAL ARTICLE

Hypertensive women with the metabolic syndrome are at risk of renal insufficiency more than men in general population P Korhonen1, P Aarnio2, R Vesalainen3, T Saaresranta4,5, H Kautiainen6, S Ja¨rvenpaä¨6 and I Kantola7 1

Central Satakunta Health Federation of Municipalities, Harjavalta, Finland; 2Department of Surgery, Satakunta Hospital District, Pori, Finland; 3Department of Medicine, University of Turku and Pulssi Medical Center, Turku, Finland; 4Department of Pulmonary Diseases, Turku University Hospital, Turku, Finland; 5 Sleep Research Unit, Department of Physiology, University of Turku, Turku, Finland; 6Medcare Foundation, Aä¨nekoski, Finland and 7Department of Medicine, Turku University Hospital, Turku, Finland

The prevalence of renal insufficiency in hypertensive participants without comorbidities affecting renal function is unknown. The objective of this study was to assess the prevalence and predictors of renal insufficiency in general hypertensive population. We examined 994 hypertensive participants aged 45–70 years without previously diagnosed diabetes, cardiovascular disease or chronic kidney disease. Renal insufficiency was defined as estimated glomerular filtration rate o60 ml min1 per 1.73 m2 by the Modification of Diet in Renal Disease formula. The metabolic syndrome was defined according to the International Diabetes Federation and the US National Cholesterol Education Program Third Adult Treatment Panel criteria. Glucose homoeostasis was assessed with an oral glucose tolerance test. The prevalence of renal insufficiency was 6.7% (95% con-

fidence interval (CI) 5.3–8.5). In a multivariate model, the presence of renal insufficiency was predicted by female gender (odds ratio (OR) 3.57 (95% CI 1.90–6.72)), older age (OR 1.13 (95% CI 1.07–1.18)), use of diuretics (OR 2.13 (95% CI 1.19–3.82)) and metabolic syndrome (OR 2.79 (95% CI 1.34–5.79)). Newly diagnosed diabetes or prediabetes did not predict renal insufficiency. The prevalence of renal insufficiency was found to be lower than previously reported in hypertensive general population. Metabolic syndrome, but not newly diagnosed diabetes or prediabetes per se, was strongly associated with renal insufficiency especially in women. Renal insufficiency was also associated with the use of diuretics, but the clinical relevance of this finding needs to be clarified. Journal of Human Hypertension (2009) 23, 97–104; doi:10.1038/jhh.2008.115; published online 11 September 2008

Keywords: renal insufficiency; metabolic syndrome; diabetes; prediabetes

Introduction In population-based cohort studies, even mild-tomoderate chronic kidney disease has been associated with a significant increase in cardiovascular risk.1–3 The introduction of estimated glomerular filtration rate (eGFR) calculated using simple formulas, the Cockroft–Gault (C–G) formula4 and the four-variable Modification of Diet in Renal Disease (MDRD) formula,5 has renewed interest in reliable measurement of renal excretory function also in primary care. These simple formulas help to identify patients with renal insufficiency who may have been earlier overlooked if the renal function had

Correspondence: Dr P Korhonen, Specialist in Internal Medicine, Central Satakunta Health Federation of Municipalities, Jokikatu 3, Harjavalta 29200, Finland. E-mail: [email protected] Received 3 July 2008; revised 14 August 2008; accepted 18 August 2008; published online 11 September 2008

been assessed by serum creatinine alone. An eGFR level 30–59 ml min1 per 1.73 m2 represents loss of half or more of the adult level of normal kidney function6 and is considered a moderately decreased glomerular filtration rate.7 The European 2007 guidelines for the management of arterial hypertension list an eGFR level o60 ml min1 per 1.73 m2 and a slight increase in plasma creatinine (women: 107–124 mmol l1; men: 115–133 mmol l1) among evidence of subclinical organ damage and recommend that creatinine clearance should be estimated in all hypertensive patients with the C–G or the MDRD formula.8 Hypertension, diabetes and cardiovascular diseases are well-established risk factors for chronic kidney disease.7 In this study, we assessed the prevalence and determinants of renal insufficiency defined as eGFRo60 ml min1 in a cohort of hypertensive participants in the general population. To minimize the interaction between hypertension, diabetes and cardiovascular diseases, we excluded

Hypertension and renal insufficiency P Korhonen et al 98

patients with known diabetes as well as patients with diagnosed cardiovascular or renal disease.

Methods Subjects

The study sample of hypertensive participants was drawn from the participants of the population survey, the Harmonica Project, which was carried out in the rural towns of Harjavalta and Kokema¨ki in southwestern Finland from autumn 2005 to autumn 2007. A risk factor survey, tape for the measurement of waist circumference and type 2 diabetes risk assessment form (FINnish Diabetes RIsk SCore, FINDRISC, available from www.diabetes.fi/english)9 were mailed to all inhabitants aged 45–70 years (n ¼ 6013). In the risk factor survey, participants were asked for waist circumference measured at the level of umbilicus, latest blood pressure, use of antihypertensive medication, gestational diabetes or hypertension, history of coronary artery disease, myocardial infarction or stroke of their parents or siblings. The participants were asked to mail the risk factor survey back to the health centre if they were willing to participate in the project. Participation and all the tests included were free of charge for the participants. Participation rate was 74.0% (4450/6013). Participants with above-mentioned risk factors or at least 15 points (X12 points in Harjavalta) in the FINDRISC (n ¼ 2752) were invited for laboratory tests and further examinations. A total of 1130 hypertensive participants were identified. For the analyses described here, we excluded participants with known diabetes, diagnosed cardiovascular or renal disease (polycystic kidney disease, chronic nephropathies, one single kidney), yielding an analytic cohort of 994 individuals.

Measurements

Renal function was estimated by the plasma creatinine level (enzymatic method, Olympus AU640, Japan) and eGFR. As our test method of plasma creatinine has been calibrated to be traceable to isotope dilution mass spectrometry, we calculated eGFR using the recently developed modified fourvariable MDRD Study equation 175 (PCr/88.4)1.154 (Age)0.203 (0.742 if women) (1.21 if black), where PCr ¼ plasma creatinine in mmol l1, and age is expressed in years.10 Race was not applicable to our study because all patients were white. As the MDRD formula is based on data from patients with advanced renal failure, the results may not be valid in patients with normal or near normal glomerular filtration rates. Therefore, we report only eGFR levels o60 ml min1 per 1.73 m2 as renal insufficiency. To test the agreement of the two eGFR methods, we also assessed eGFR by the C–G formula.4 Journal of Human Hypertension

Plasma glucose levels, creatinine levels and lipid profiles were determined in blood samples that were obtained after at least 12 h of fasting. Oral glucose tolerance test was performed by measuring fasting plasma glucose and 2-h plasma glucose after ingestion of a glucose load of 75 g anhydrous glucose dissolved in water. Glucose disorders were classified according to the World Health Organization 1999 criteria, which were updated in 2006.11 On the basis of 2-h post-load plasma glucose, individuals were classified into categories of newly diagnosed diabetes (type 2 diabetes mellitus), impaired glucose tolerance and normal glucose tolerance if their 2-h plasma glucose concentrations were X12.2, 8.9–12.1 and o8.9 mmol l1, respectively. Impaired fasting glucose was diagnosed if the fasting plasma glucose was X6.1 mmol l1 and the 2-h plasma glucose was o8.9 mmol l1. Blood pressure was measured by a trained nurse with a calibrated mercury sphygmomanometer with participants in a sitting posture, after resting for at least 5 min. In each participant, the mean of the two readings taken at intervals of at least 2 min was used in the study. Pulse pressure was calculated by subtracting the mean diastolic blood pressure from the mean systolic blood pressure. If the mean systolic blood pressure was X140 mm Hg or the mean diastolic blood pressure X90 mm Hg, participants were taught to use an automatic validated blood pressure monitor (Omron Healthcare Co., Ltd, 24 Yamanouchi Yamanoshitacho, Ukyo-ku, Kyoto, Japan) that was lent them for home blood pressure monitoring. In the participants whose arm circumference was 432 cm, a larger cuff was used. The participants were instructed to take duplicate blood pressure measurements in the seated position after 5 min of rest in the morning and evening for 1 week. The recorded measurements except those from the first day were used to calculate the mean home blood pressure. Hypertension was diagnosed if any of the following conditions were met: (1) the patient was already taking antihypertensive therapy; (2) the mean systolic blood pressure taken by the nurse was X140 mm Hg or the mean diastolic blood pressure was X90 mm Hg, and the mean of home blood pressure monitoring was X135 mm Hg systolic or X85 mm Hg diastolic. Height, weight and waist circumference were measured by the nurse. Body mass index was calculated as weight (kg) divided by the square of height (m2). The metabolic syndrome was diagnosed according to the criteria of the International Diabetes Federation (IDF)12 and the US National Cholesterol Education Program Third Adult Treatment Panel (ATPIII)13 (Table 1).


Table 1 Diagnostic criteria of the metabolic syndrome Clinical measure

ATPIII (2001) any three of the following

IDF (2005) WC+any two of the following

Waist circumference

488 cm in women 4102 cm in men X130/85 mm Hg 45.6 mmol l1a or T2D X1.7 mmol l1 o1.29 mmol l1 in women o1.03 mmol l1 in men

X80 cm in women X94 cm in men X130/85 mm Hg or hypertension Rx X5.6 mmol l1 or T2D X1.7 mmol l1 or TG Rx o1.29 mmol l1 in women o1.03 mmol l1 in men or HDL cholesterol Rx

Blood pressure Glucose Triglycerides HDL cholesterol

Abbreviations: ATPIII, the US National Cholesterol Education Program Third Adult Treatment Panel; HDL, high-density lipoprotein; IDF, International Diabetes Federation; IGT, impaired glucose tolerance; T2D, type 2 diabetes mellitus; TG, triglycerides; Rx, regimen; WC, waist circumference. a The 2001 definition identified fasting plasma glucose of X6.1 mmol l1 as elevated. This was modified in 2004 to be X5.6 mmol l1.

Informed consent

The study protocol and consent forms were reviewed and approved by the ethics committee of Satakunta hospital district. All participants provided written informed consent for the project and subsequent medical research. Statistical analysis

The data are presented as means with standard deviations or as counts with percentages. The most important results are given with the 95% confidence intervals (CIs). Statistical comparison between groups in measures with binary distribution was made by w2 or Fischer’s exact test, when appropriate. The independent samples t-test was used for continuous variables, except for biochemical variables, which were analysed by bootstrapped type t-test due to their skewed distributions. To determine predictors of low eGFR, univariate and multivariate forward stepwise logistic regression analysis was applied. Correlations were estimated by Spearman’s correlation coefficient method. Statistical analysis was made with the statistical software Stata 10.0 (StataCorp., College Station, TX, USA). Role of the funding source

This work was supported by the State Provincial Office of Western Finland, the Central Satakunta Health Federation of Municipalities, the Finnish Cultural Foundation and the Ida Montin Foundation.

Results We evaluated 994 hypertensive participants (mean age 59±7 years, 54.1% women) without previously known diabetes, cardiovascular or renal disease. According to oral glucose tolerance test, 65 of them (6.5%) had new type 2 diabetes mellitus, 205 (20.6%) had impaired glucose tolerance and 158 (15.9%) had impaired fasting glucose. The prevalence of the metabolic syndrome was 69.9% (69.5% in women, 70.4% in men) according to the IDF

criteria and 60.4% (60.8% in women, 59.9% in men) according to the ATPIII criteria. Of the 538 women, only six (1.1%) had plasma creatinine X107 mmol l1 (range 83–114 mmol l1). Of the 456 men, 11 (2.4%) had plasma creatinine X115 mmol l1 (range 111–132 mmol l1). According to the MDRD formula, the crude prevalence of renal insufficiency defined as eGFRo60 ml min1 per 1.73 m2 was 6.7% (95% CI: 5.3–8.5) (67/994), 10.0% (95% CI: 7.6–12.9) in women (54/538) and 2.9% (95% CI: 1.5–4.8) in men (13/456) (age-adjusted Po0.001). None had eGFRo30 ml min1 per 1.73 m2. The mean eGFR by the MDRD formula mean was 77 ml min1 (s.d. 15) in women and 86 ml min1 (s.d. 16) in men. According to the C–G formula, the crude prevalence of renal insufficiency in women was 4.8% (95% CI: 3.2–7.0) (26/538) and in men 0.9% (95% CI: 0.2–2.2) (4/456). The mean eGFR by the C–G formula was 97 ml min1 (s.d. 28) in women and 111 ml min1 (s.d. 30) in men. Correlation between the MDRD formula and the C–G formula was 0.70 (95% CI: 0.67–0.73). Risk factors for renal insufficiency

Table 2 shows the characteristics of the patients according to eGFR assessed by the MDRD formula. Patients with eGFRo60 ml min1 per 1.73 m2 tended to be more often female, elderly, to have higher body mass index and diastolic blood pressure or present metabolic syndrome and use of diuretics. Neither fasting plasma glucose nor 2-h post-load glucose values showed significant differences in patients with renal insufficiency vs patients with preserved renal function. Participants with metabolic syndrome were more likely to have renal insufficiency than participants without metabolic syndrome (P ¼ 0.002 for the definition of IDF, P ¼ 0.05 for the definition of ATPIII). In patients with metabolic syndrome according to the IDF criteria, the age-adjusted prevalence of renal insufficiency was 10.2% (95% CI 7.3–14.0) in women and 2.5% (95% CI 1.2–5.2) in men (age-adjusted Po0.001 for the difference Journal of Human Hypertension


Table 2 Baseline characteristics of study participants according to estimated glomerular filtration rate (eGFR) by the modification of diet in renal disease formula eGFR o60 ml min1 n ¼ 67 Demographic Number of female participants (%) Age in years, mean (s.d.) Weight in kg, mean (s.d.) Body mass index in kg/m2, mean (s.d.) Waist circumference in cm, mean (s.d.) Women Men Clinical Blood pressure in mm Hg, mean (s.d.) Systolic Diastolic Pulse pressure Metabolic syndrome present (%) IDF ATPIII Biochemical Total cholesterol in mmol l1, mean (s.d.) LDL cholesterol in mmol l1, mean (s.d.) Triglycerides in mmol l1, mean (s.d.) Fasting glucose in mmol l1, mean (s.d.) 2-h glucose in mmol l1, mean (s.d.)

54 64 83.8 31.5

(80.6) (5) (13.1) (5.7)

P-value X60 ml min1 n ¼ 927

484 59 85.5 29.9

(52.2) (7) (16.6) (5.0)

o0.001 o0.001 0.40 0.01

98.7 (12.6) 101.7 (6.5)

95.2 (13.5) 103.4 (11.2)

0.07 0.57

150.6 (17.2) 87.9 (10.0) 62.8 (13.8)

153.0 (17.4) 90.5 (8.4) 62.4 (14.6)

0.29 0.01 0.87

58 (86.6) 48 (71.6)

637 (68.7) 552 (59.5)

0.002 0.05

5.35 3.19 1.48 5.72 8.19

(0.98) (0.81) (0.73) (0.68) (2.26)

5.30 3.19 1.42 5.71 7.85

(0.92) (0.80) (0.73) (1.08) (2.48)

0.70 0.98 0.54 0.92 0.25

31 20 9 4

(46.3) (29.9) (13.4) (6.0)

333 123 127 27

(35.9) (13.3) (13.7) (2.9)

0.09 o0.001 0.95 0.15

Current medication (%) ACE inhibitor or ATR antagonist Diuretic Statin NSAIDs

Abbreviations: ACE, angiotensin-converting enzyme; ATPIII, Adult Treatment Panel III; ATR, angiotensin receptor; IDF, International Diabetes Federation; NSAIDs, non-steroidal anti-inflammatory drugs.

between the genders). When the ATPIII criteria were used, the age-adjusted prevalence of renal insufficiency among those with metabolic syndrome was 9.8% (95% CI 6.8–13.8) in women and 2.4% (95% CI 1.1–5.3) in men (age-adjusted Po0.001). Among the 54 women with renal insufficiency, 53 (98.1%) had waist circumference X80 cm and 40 (74.1%) had waist circumference 488 cm. Among the 13 men with renal insufficiency, 12 (92.3%) had waist circumference X94 cm and seven (53.8%) had waist circumference 4102 cm. Ten of the 67 (14.9%) patients with renal insufficiency fulfilled the IDF criteria of metabolic syndrome, but not the ATPIII criteria because of the difference in the cutoff value of waist circumference (Table 1). In participants without metabolic syndrome, the age-adjusted prevalence of renal insufficiency was 3.5% (95% CI 1.6–7.3) in women and 1.1% (95% CI 0.2–4.5) in men when the IDF criteria were used. When the ATPIII criteria were used, the age-adjusted prevalence of renal insufficiency was 5.5% (95% CI 3.2–9.4) in women and 1.5% (95% CI 0.5–4.6) in men. There was no significant difference between genders in the prevalence of renal insufficiency among participants without metabolic syndrome as defined by either of the criteria used. Journal of Human Hypertension

The use of diuretics was more common in patients with renal insufficiency than in patients with preserved eGFR (29.9 vs 13.3%, Po0.001; Table 2), but no difference in the use of diuretics was found by gender (29.6% in women vs 30.8% in men with renal insufficiency and 14.5% in women vs 12.0% in men without renal insufficiency). Treatment with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or statins showed no statistically significant differences among patients with renal insufficiency or preserved renal function. Daily use of nonsteroidal anti-inflammatory drugs was rare and was not different in the presence of renal insufficiency. When adjusted for age and sex, renal insufficiency was associated with body mass index, use of diuretics and the presence of metabolic syndrome defined by the IDF and ATPIII criteria. In multivariate analysis, female gender (odds ratio (OR) 3.57 (95% CI 1.90–6.72)), age (OR 1.13 (95% CI 1.07–1.18)), use of diuretics (OR 2.13 (95% CI 1.19–3.82)) and the metabolic syndrome (OR 2.79 (95% CI 1.34–5.79)) were entered in the logistic regression model with forward selection (Table 3).


Table 3 Univariate and multivariate predictors of low estimated glomerular filtration rate (eGFRo60 ml min1) by the modification of diet in renal disease formula Univariatea

Variables

Female Age BMI

Multivariateb,c

Multivariatec,d

OR (95% CI)

P-value

OR (95% CI)

P-value

OR (95% CI)

P-value

3.52 (1.88–6.57) 1.14 (1.09–1.19) 11.05 (1.01–1.10)

o0.001 o0.001 0.019

3.57 (1.90–6.72) 1.13 (1.07–1.18)

o0.001 o0.001

3.53 (1.88–6.62) 1.13 (1.07–1.18)

o0.001 o0.001

2.13 (1.19–3.82)

0.011

2.31 (1.30–4.12)

0.004

2.79 (1.34–5.79)

0.006

Blood pressure Systolic Diastolic Total cholesterol Triglycerides

0.99 0.99 0.99 1.33

(0.97–1.00) (0.96–1.02) (0.75–1.32) (0.94–1.88)

Glucose homoeostasis Normal IFG IGT T2D

1.00 1.51 0.92 0.79

(reference) (0.75–3.07) (0.48–1.75) (0.26–2.37)

Current medication ACE inhibitor or ATR antagonist Diuretic Statin NSAID

1.47 2.31 0.71 1.48

(0.88–2.47) (1.30–4.12) (0.34–1.50) (0.48–4.57)

0.14 0.004 0.37 0.49

Metabolic syndrome IDF ATPIII

2.98 (1.44–6.17) 1.79 (1.02–3.15)

0.003 0.042

0.062 0.53 0.96 0.11 0.59

Abbreviations: ACE, angiotensin-converting enzyme; ATPIII, Adult Treatment Panel III; ATR, angiotensin receptor; BMI, body mass index; IDF, International Diabetes Federation; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; NSAIDs, non-steroidal anti-inflammatory drugs; T2D, type 2 diabetes mellitus. a Adjusted for age and sex, when appropriate. b Model included other variables and metabolic syndrome definition of IDF. c Forward selection. Only variables that entered the model are shown. d Model included other variables and metabolic syndrome definition of ATPIII.

Discussion In this cohort of hypertensive participants from general population, the prevalence of renal insufficiency defined as eGFRo60 ml min1 per 1.73 m2 was 6.7% measured by the MDRD formula and 3.0% measured by the C–G formula, when known diabetics and people with cardiovascular or renal disease were excluded. As the MDRD formula, unlike the C–G formula, is not biased by body weight, it is probably more accurate in our study cohort in which most patients were overweight or obese according to body mass index. If we would have estimated renal function on the basis of plasma creatinine alone, we had missed three-fourth of the patients with renal insufficiency. Thus, eGFR should be estimated in every hypertensive patient also in general practice. The prevalence of renal insufficiency in hypertensive participants in our study was much lower than that in the two Spanish studies in a primary care setting.14,15 In these multicentre studies, the prevalence of eGFRo60 ml min1 per 1.73 m2 was over 20% according to the MDRD study formula. In the study by Gomez et al.,14 the study population consisted of overweight or obese hypertensives of

whom 32.9% had previously diagnosed diabetes and 3.6% had chronic kidney disease. In the study by Redon et al.,15 41% of the enrolled patients had type 2 diabetes mellitus, 49% had impaired fasting glucose and only 18% had normal fasting glucose. By excluding the patients with known diabetes, cardiovascular or renal disease, we identified a cohort of hypertensives with no known comorbidities affecting renal function, which probably explains the difference in the prevalence of renal insufficiency between the studies. The strength of our study is that all plasma creatinine assays were made in one laboratory with one method that has been calibrated to be traceable to isotope dilution mass spectrometry, the gold standard. Improved accuracy of eGFR is obtainable by using isotope dilution mass spectrometry correction especially in the early stages of chronic kidney disease.16 Non-standardized creatinine measurements from different laboratories may differ systematically by as much as 27 mmol l1.17 A difference of this magnitude would have a large effect on the results of the eGFR equations. As our results are derived from only one visit and a single creatinine measurement, it is not possible to confirm the chronicity of renal insufficiency in our Journal of Human Hypertension


patients. It has been estimated that 25–30% of participants initially categorized as stage 3 chronic kidney disease (eGFR 30–59 ml min1 per 1.73 m2) will subsequently no longer fall into this category when repeated measurements are obtained over 3 months after the ‘qualifying’ test.18 We used oral glucose tolerance test to detect previously undiagnosed glucose disorders in our study patients. Only 57% of them had normal glucose homoeostasis, but the fasting or 2-h postload glucose values were not related to decreased eGFR. Although we cannot reliably assess the true duration of newly diagnosed glucose disorders in this cross-sectional study, our results nevertheless suggest that new-onset diabetes or prediabetes does not independently affect renal function in hypertensive patients. This highlights the importance of early prevention, diagnosis and treatment of impaired glucose metabolism in hypertensive patients to prevent the deleterious effects of long-lasting diabetes on renal dysfunction. The predominance of women in the renal insufficiency group of our study is noteworthy, but in concordance with other large-scale studies in hypertensive15,19 as well as diabetic participants.20,21 However, the risk of renal insufficiency in women in our cohort was also associated with metabolic syndrome; the prevalence of renal insufficiency was 3.5 times higher in women with metabolic syndrome than in women without metabolic syndrome and over four times higher than in men with metabolic syndrome. Chen et al.22 were the first to demonstrate a strong relationship between the metabolic syndrome— defined by the ATPIII criteria13—and the risk for chronic kidney disease in an analysis using the US Third National Health and Nutrition Examination Survey data set. In our study, the IDF definition of metabolic syndrome was a better predictor of renal insufficiency than the ATPIII definition. This is due to the cutoff value of waist circumference, which is the only difference between the two definitions (Table 1). In our study population of 994 participants, metabolic syndrome was diagnosed in 695 participants using the IDF criteria and in 600 participants using the ATPIII criteria. Among 67 participants with renal insufficiency, there were 10 who had metabolic syndrome according to the IDF criteria, but not according to the ATPIII criteria, just because these eight women and two men had waist circumferences of 80–88 and 94–102 cm, respectively. It has been demonstrated in autopsy studies23,24 that women have fewer glomeruli than men and that the number of nephrons is reduced in white patients with primary hypertension.25 Susceptibility to renal failure may be determined in large part by glomerular number.24 Thus, in hypertensive women with reduced nephron numbers, the metabolic syndrome might be ‘the final straw to break the camel’s back’. Journal of Human Hypertension

On the other hand, in most countries including Finland, the incidence of end-stage renal disease is higher in men than in women. Therefore, it seems possible that the MDRD equation underestimates true renal function in women. In the large population-based cohort of the Atherosclerosis Risk in Communities study, the metabolic syndrome defined by the ATPIII criteria was independently associated with increased risk of incident chronic kidney disease in non-diabetic adults without cardiovascular disease at baseline.26 The cohort was followed for 9 years during which 10% of participants with metabolic syndrome developed chronic kidney disease (that is, eGFR o60 ml min1 per 1.73 m2 calculated by the fourvariable MDRD formula) compared with 4% of participants without metabolic syndrome. In our study, 600 out of 994 studied participants fulfilled the metabolic syndrome criteria of the ATPIII. If 10% of them would develop chronic kidney disease in 9 years, the amount of patients with renal insufficiency would double in the near future. Although controlling hypertension is the most important intervention to slow the progression of renal disease,27 the practitioners in primary care have to focus on all the components of the metabolic syndrome to prevent chronic kidney disease along with cardiovascular disease in their hypertensive patients. In our study, reduced renal function was associated with the use of diuretics. Although we cannot assess the causality of this association solely from our cross-sectional study, our results are in concordance with prospective studies addressing the long-term effects of diuretics on renal function in hypertensive patients. In the European Working Party on High Blood Pressure in the Elderly trial, serum creatinine increased more in patients with diuretics than in the placebo group.28 In the Treatment of Mild Hypertension Study, serum creatinine increased with the use of thiazides, but was reduced by other types of treatment.29 In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, estimated creatinine clearance was significantly better preserved with amlodipine than with thiazide or lisinopril.30 Results from the Intervention as a Goal in Hypertensive Treatment study show that renal function is better preserved with calcium channel blocker than with the diuretic combination hydrochlorothiazide– amiloride.31 On the other hand, thiazide diuretics may also increase serum creatinine concentration by reducing tubular secretion of creatinine.32 Therefore, it is currently unknown whether the use of diuretics is truly associated with an increased risk of subclinical organ damage in the kidney. In conclusion, we document that the metabolic syndrome defined with the IDF and the ATPIII criteria, but not newly diagnosed diabetes or prediabetes per se, is strongly associated with renal insufficiency in women. After excluding patients


with known diabetes, cardiovascular and renal diseases, the prevalence of renal insufficiency, defined by the MDRD formula as eGFRo60 ml min1 per 1.73 m2, was found to be lower in our study than reported earlier in hypertensive general population with diabetics.14,15 Decreased renal function was also associated with the use of diuretics, but the clinical relevance of this association is currently unknown and needs to be clarified in further studies. What is known about this topic K The prevalence of renal insufficiency in general hypertensive population is high. K Estimated glomerular filtration rate is a more reliable measurement of renal function than plasma creatinine. What this study adds K In hypertensive participants without known diabetes, cardiovascular or renal disease, the prevalence of eGFRo60 ml min1 per 1.73 m2 is lower than that reported earlier. K The metabolic syndrome, but not newly detected diabetes or prediabetes per se, is strongly associated with renal insufficiency in women. Abbreviation: eGFR, estimated glomerular filtration rate.

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