Microalbuminuria in treated hypertensives: Only a mirror image of cardiovascular risk?

Figures & data

Table I.  Cardiovascular risk factors and disease in men and women with treated hypertension in the Nord-Trøndelag Health Study (HUNT). Values are mean of all in sex, and standard deviation (SD) unless otherwise indicated.

	Womenn = 3062	Menn = 2307
Albumin–creatinine ratio[mean of 3 samples] (mg mmol^−1)	1.5 (2.4)	1.9 (3.1)***
Age (years)	66.7 (11.3)	64.3 (11.3) ***
Systolic blood pressure (mmHg)	157.8 (22.4)	153.0 (21.6) ***
Diastolic blood pressure (mmHg)	87.1 (12.5)	89.3 (12.1) ***
Pulse pressure (mmHg)	70.8 (18.1)	63.6 (16.6) ***
Blood pressure > 140/90 (%)	79.0	74.3***
Years with antihypertensive medication	11.9 (10.1)	10.0 (8.6) ***
Body mass index (kg m^−2)	29.1 (4.9)	28.0 (3.8) ***
Waist–hip ratio	0.83 (0.1)	0.93 (0.1) ***
Cholesterol (mmol L^−1)	6.7 (1.3)	6.2 (1.1) ***
HDL cholesterol (mmol L^−1)	1.4 (0.4)	1.2 (0.4) ***
Cholesterol/HDL ratio	5.1 (1.7)	5.5 (1.7) ***
Triglycerides^1 (nmol L^−1)	2.2 (1.2)	2.1 (1.2) *
s-Glucose^1 (mmol L^−1)	5.7 (1.0)	5.7 (1.1)
s–Creatinine (µmol L^−1)	87.5 (14.4)	102.0 (19.4) ***
Daily smoking (%)	15.4	20.4***
Cigarette pack years (pack/day year) prior or current	4.1(8.1)	13.0 (15.4)***
Cardiovascular disease (%)	21.2	34.9***
Education > 12 years (%)	7.0	13.4***

¹Non-fasting. Sex difference: *p < 0.05, **p < 0.01, ***p < 0.001.

Table II.  Prevalence (%) of microalbuminuria (albumin–creatinine ratio > 2.5 mg mmol⁻¹, mean of three samples) in treated hypertensives, by sex and age groups.

	Women		Men
	All	MA	All	MA	Sex difference
Age	n	%	n	%	p*
20–49 years	243	8.2	251	8.8	0.831
50–59 years	534	7.5	477	9.4	0.266
60–69 years	854	9.5	731	14.2	0.003
70 years +	1431	15.0	848	24.9	<0.001
Total	3062	11.6	2307	16.6	<0.001
Test for age trend	p < 0.001		p < 0.001
Blood pressure > 160/90 mmHg	1651	14.8	1232	20.2	<0.001
Blood pressure ≤ 160/90 mmHg	1411	7.8	1075	12.4	<0.001
Cardiovascular disease	648	14.2	806	18.4	0.033
No cardiovascular disease	2414	10.9	1501	15.6	<0.001
Blood pressure > 160/90 mmHg and/or cardiovascular disease	1974	13.9	1708	18.5	<0.001
Blood pressure ≤ 160/90 mmHg and no cardiovascular disease	1088	7.4	599	11.0	0.010

*Pearson's chi-squared.

Table III.  Sex differences in mean urine albumin–creatinine ratio (95% CI) by various age groups. Sex specific quartiles and no/yes groups.

	Quartile	Women	Albumin–creatinine ratio (mg mmol^−1)		Men	Albumin–creatinine ratio (mg mmol^−1)
	No/Yes	n	Mean (95% CI)	p^*	n	Mean (95% CI)	p^*
Age groups (years)	20–49	243	1.25 (1.03–1.48)	0.004	251	1.41 (1.05–1.77)	<0.001
	50–59	534	1.18 (1.02–1.33)		477	1.22 (1.06–1.38)
	60–69	854	1.34 (1.21–1.47)		731	1.70 (1.51–1.90)
	70 +	1431	1.80 (1.65–1.95)		848	2.61 (2.35–2.87)
Pulse pressure (mmHg)	Q1	760	1.17 (1.06–1.28)	<0.001	562	1.32 (1.15–1.50)	<0.001
	Q2	733	1.46 (1.29–1.63)		569	1.52 (1.31–1.73)
	Q3	776	1.54 (1.38–1.70)		582	2.02 (1.76–2.28)
	Q4	789	1.89 (1.68–2.10)		589	2.72 (2.38–3.06)
Blood pressure	No	642	1.17 (1.04–1.31)	<0.001	593	1.36 (1.19–1.53)	<0.001
>140/90 (mmHg)	Yes	2420	1.61 (1.51–1.71)		1714	2.09 (1.93–2.25)
Blood pressure	No	1411	1.22 (1.12–1.31)	<0.001	1075	1.42 (1.29–1.54)	<0.001
>160/90 (mmHg)	Yes	1651	1.80 (1.66–1.91)		1232	2.33 (2.12–2.54)
Years of antihypertensive medication	Q1	522	1.29 (1.14–1.43)	0.001	308	1.48 (1.23–1.72)	0.001
	Q2	595	1.29 (1.13–1.46)		599	1.63 (1.40–1.85)
	Q3	604	1.44 (1.26–1.62)		476	2.12 (1.78–2.45)
	Q4	614	1.81 (1.57–2.07)		490	2.24 (1.93–2.54)
Cardiovascular disease	No	2414	1.44 (1.35–1.53)	<0.001	1501	1.77 (1.63–1.92)	0.006
(MI, angina, stroke)	Yes	648	1.81 (1.58–2.05)		806	2.15 (1.90–2.39)
Daily smoking	No/missing	2589	1.46 (1.38–1.56)	0.004	1836	1.83 (1.69–1.98)	0.032
	Yes	473	1.81 (1.57–2.05)		471	2.18 (1.89–2.48)
Cigarette pack years (pack/day year)	Q1	209	1.21 (1.02–1.39)	<0.001	308	1.70 (1.35–2.04)	0.039
	Q2	191	1.41 (1.00–1.82)		319	1.84 (1.49–2.19)
	Q3	224	1.58 (1.24–1.92)		318	1.78 (1.48–2.08)
	Q4	215	2.00 (1.61–2.40)		315	2.29 (1.85–2.73)
Cholesterol/HDL ratio	Q1	762	1.37 (1.22–1.51)	0.001	574	1.85 (1.58–2.12)	0.315
	Q2	764	1.45 (1.30–1.61)		562	1.92 (1.66–2.18)
	Q3	757	1.43 (1.27–1.58)		566	1.78 (1.53–2.02)
	Q4	772	1.80 (1.60–2.02)		591	2.04 (1.79–2.29)
BMI (kg m^−2)	Q1	741	1.56 (1.40–1.72)	0.744	544	2.09 (1.79–2.39)	0.985
	Q2	758	1.49 (1.32–1.67)		580	1.73 (1.52–1.95)
	Q3	762	1.39 (1.23–1.55)		569	1.63 (1.41–1.85)
	Q4	755	1.60 (1.41–1.79)		596	2.09 (1.83–2.36)
s-Creatinine (µmol L^−1)	Q1	700	1.40 (1.26–1.55)	0.013	508	1.61 (1.40–1.82)	<0.001
	Q2	722	1.39 (1.24–1.54)		638	1.60 (1.41–1.79)
	Q3	823	1.52 (1.35–1.69)		565	1.64 (1.41–1.87)
	Q4	810	1.72 (1.52–1.91)		594	2.74 (2.40–3.09)
Education in groups	<10 years	2015	1.57 (1.46–1.69)	0.002	1072	1.98 (1.78–2.17)	0.602
	10–12 years	512	1.33 (1.16–1.49)		762	1.68 (1.49–1.88)
	>12 years	189	1.00 (0.83–1.16)		283	1.86 (1.45–2.26)

^*p-values from independent samples t-tests, highest and lowest alternative or No and Yes compared.

Table IV.  HUNT 2: Self reported antihypertensive medication group (ATC code): Mean urine albumin–creatinine ratio.

	Hypertension drug users		Women	Mean age	Mean albumin–creatinine ratio
AT drug groups with combinations	n	%	%	years	(mg mmol^−1)
One drug
Antihypertensives (C02A,–C,–D)*	273	5.1	51.3	61.9	1.61
Diuretics (C03)	485	9.0	74.6	72.3	1.45
Beta-blocking agents (C07)	907	16.9	53.4	62.7	1.40
Calcium channel blockers (C08)	857	16.0	56.7	64.9	1.84
Agents acting on the Renin–angiotensin system (C09)	647	12.1	52.2	62.5	1.61
One drug, total	3169	59.0	57.1	64.7	1.59
Two drugs combined
C02A,–C,–D* + C03	52	1.0	73.1	69.1	0.95
C02A,–C,–D* + C07	62	1.2	50.0	63.5	1.73
C02A,–C,–D* + C08	44	0.8	40.9	66.2	2.76
C02A,–C,–D* + C09	52	1.0	40.4	61.5	1.29
C03 + C07	174	3.2	74.7	69.9	1.31
C03+ C08	95	1.8	70.5	70.4	2.33
C03+ C09	118	2.2	60.2	67.8	1.65
C07 + C08	315	5.9	57.8	67.3	1.68
C07 + C09	169	3.1	49.1	64.6	2.03
C08 + C09	174	3.2	50.0	62.9	2.07
Two drugs combined, total	1255	23.4	58.0	66.6	1.77
Three drugs combined, total	212	3.9	54.7	65.9	1.47
Total on AT drugs	4641	86.4	57.3	65.2	1.63
No self reported drugs/Other drugs	728	13.6	55.6	68.5	2.00

*Anti-adrenergic agent with central effect, anti-adrenergic agent with peripheral effect and anti-hypertensives with effect in the arteriole smooth muscle.

Table Va.  General linear model with ln urine–albumin–creatinine ratio (mg mmol⁻¹) as the dependent variable.

Men ≥ 20 years taking antihypertensive medication in The Nord-Trøndelag Health Study (HUNT).
		Regression statistics
	Independent variables^*	β	p-value
All men, n = 950	Age	0.009	0.011
	s-Creatinine	0.005	0.011
	Pulse pressure	0.010	<0.001
	Cigarette pack years	0.005	0.009
	Cardiovascular disease	0.159	0.022
	Years of antihypertensive medication	0.008	0.033
	Antihypertensive medication in 25 groups	Fixed factor	0.007
Blood pressure ≤ 160/90,
n = 463	Age	0.010	0.042
	BMI	0.029	0.009
	Cardiovascular disease	0.234	0.012
Without cardiovascular disease, n = 623	Pulse pressure	0.010	0.001
	s-Creatinine	0.006	0.005
	Antihypertensive medication in 25 groups	Fixed factor	0.008
Blood pressure ≤ 160/90 without cardiovascular disease, n = 267	No significant variable

^*Independent variables entered: age, pulse pressure, cardiovascular disease, cholesterol/HDL–cholesterol ratio, BMI, education, years of antihypertensive medication, cigarette pack years, s-creatinine, and antihypertensive medication in 25 subgroups. All adjusted for.

Table Vb.  General linear model with ln urine–albumin–creatinine ratio (mg mmol⁻¹) as the dependent variable.

Women ≥ 20 years taking antihypertensives medication in The Nord-Trøndelag Health Study (HUNT).
		Regression statistics
	Independent variables^*	β	p-value
All women, n = 633	Pulse pressure	0.009	<0.001
	Cigarette pack years	0.012	0.002
	Antihypertensive medication in 25 groups	Fixed factor	0.002
Blood pressure ≤ 160/90,
n = 323	Antihypertensive medication in 25 groups	Fixed factor	0.018
Without cardiovascular disease, n = 532	Pulse pressure	0.007	0.007
	Cigarette pack years	0.013	0.002
Blood pressure ≤ 160/90 without cardiovascular disease, n = 271	No significant variable

^*Independent variables entered: age, pulse pressure, cardiovascular disease, cholesterol/HDL–cholesterol ratio, BMI, education, years of antihypertensive medication, cigarette pack years, s-creatinine, and antihypertensive medication in 25 subgroups. All adjusted for.