Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk of a future first-ever myocardial infarction in women

Figures & data

Figure 1. Kidney with normal function and normal glomeruli, and examples of renal glomerular function impairment caused by fewer pores and shrunken pores.

Figure 2. Flowchart showing the inclusion of study participants. All incident acute myocardial infarction (MI) from individuals in Norrbotten and Västerbotten counties of northern Sweden have been recorded since 1985 under the WHO's MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) project [15]. Symptoms, biomarkers, and electrocardiogram (ECG) recordings were used for the diagnosis of MI. ECGs were evaluated according to the Minnesota code [17]. The individuals with MI were cross-checked if they had participated in population-based risk factor surveys either as part of the Västerbotten Intervention Program (VIP), the MONICA project, or the Mammary Screening Program (MSP) within the Northern Sweden Health and Disease Study (NSHDS). At the MONICA Secretariat in Luleå and Umeå, research nurses validated MI cases that had participated. Two referent individuals with no previous MI were matched to every case based on sex, age (± 2 years), time of health examination and blood sampling, as well as geographical location and sub study.

Table 1. Baseline characteristics of the study population.

	Men				Women
	(C/R)	Cases	Referents	p	(C/R)	Cases	Referents	p
Age at sample donation (years)	387/752	53.6	53.4	Matched	158/302	58.3	58.1	Matched
Lag time to MI (years)		4.3 (±2.5)	n.a.			3.4 (±2.4)	n.a.
BMI (kg/m^2)	375/727	27.1 (±3.70)	25.9 (±3.42)	<.001	86/170	26.7 (±4.71)	26.1 (±4.75)	.33
Diabetes (%)^a	361/695	11.1	5.2	.001	78/156	9.0	7.1	.80
Hypertension (%)^a	373/721	62.2	44.4	<.001	84/165	72.6	49.7	.001
Smoking (%)^a	365/723	38.4	18.1	<.001	152/297	46.7	18.9	<.001
Creatinine (µmol/L)	366/695	70.9 (±14.7)	71.6 (±10.9)	.406	154/290	61.1 (±25.6)	58.5 (±8.84)	.23
Cystatin C (mg/L)	367/696	0.95 (±0.20)	0.93 (±0.18)	.362	154/290	1.05 (±0.34)	0.96 (±0.22)	.003
eGFRcreatinine (mL/min/1.73m^2)	366/695	92.1 (±12.9)	91.2 (±10.8)	.13	154/290	86.3 (±14.2)	87.4 (±11.0)	.80
eGFRcystatin C (mL/min/1.73m^2)	367/696	83.6 (±19.8)	84.8 (±20.5)	.37	154/290	74.8 (±18.2)	80.7 (±16.35)	<.001
eGFRcystatin C/eGFRcreatinine (ratio)	366/695	0.91 (±0.20)	0.93 (±0.19)	.17	154/290	0.87 (±0.17)	0.93 (±0.17)	.001

BMI: body mass index; GFR: glomerular filtration rate; MI: myocardial infarction.

^aFor the definition, see the method section.

Numbers, means (±SD) for continuous variables, and proportions for non-continuous variables. The p-values were based on the T-test for continuous variables and the Chi-square test for independence for categorical variables. p-Values ≤.05 are shown in bold.

Figure 3. Univariable odds ratios with 95% confidence intervals for the risk of a first-ever MI in relation to glomerular function for men (▲) and women (■) separately. Risk through quartiles for (a) eGFR_creatinine, (b) eGFR_{cystatin C}, and (c) the eGFR_creatinine/eGFR_{cystatin C} ratio. p-Values ≤.05 are highlighted with *.

Table 2. Odds ratios (95% confidence intervals) for quartiles of glomerular function and risk of future MI.

	All	Men	Women
eGFRcreatinine
Q1	1.00	1.00	1.00
Q2	0.85 (0.62–1.18)	0.88 (0.59–1.30)	0.81 (0.46–1.43)
Q3	1.07 (0.77–1.50)	1.22 (0.82–1.84)	0.80 (0.44–1.45)
Q4	1.40 (0.99–1.98)	1.45 (0.96–2.19)	1.34 (0.71–2.51)
P for trend	0.03	0.03	0.47
eGFRcystatin C
Q1	1.00	1.00	1.00
Q2	0.79 (0.58–1.08)	1.04 (0.71–1.52)	0.42 (0.23–0.76)
Q3	0.80 (0.58–1.10)	0.94 (0.63–1.40)	0.61 (0.36–1.04)
Q4	0.69 (0.49–0.96)	0.91 (0.61–1.35)	0.35 (0.18–0.67)
P for trend	0.04	0.55	0.005
eGFRcystatin C/eGFRcreatinine (ratio)
Q1	1.00	1.00	1.00
Q2	0.94 (0.70–1.26)	1.01 (0.71–1.44)	0.81 (0.48–1.39)
Q3	0.59 (0.43–0.80)	0.69 (0.47–1.01)	0.40 (0.22–0.72)
Q4	0.62 (0.45–0.85)	0.74 (0.51–1.08)	0.40 (0.22–0.73)
P for trend	0.005	0.19	0.001

GFR: glomerular filtration rate; MI: myocardial infarction.

eGFR_creatinine quartile limits were for men, 84.55, 90.80, 97.93 and for women, 80.18, 86.80, 93.64 (mL/min/1.73m²). eGFR_{cystatin C} quartile limits were for men, 73.49, 82.88, 94.49 and for women, 69.92, 79.71, 89.83 (mL/min/1.73m²). eGFR_ratio quartile limits were for men, 0.825, 0.9145, 1.006 and for women, 0.8307, 0.927, 1.013. p-Values ≤.05 and odds ratios with p-values ≤.05 are shown in bold.

Table 3. Univariable and multivariable odds ratios (95% confidence intervals) for z-scores of glomerular function and risk of future MI.

	All	Men	n (C/R)	Women	n (C/R)
z (ln) eGFRcreatinine
Univariable	1.01 (0.89–1.14)	1.08 (0.93–1.26)	366/675	0.87 (0.70–1.08)	154/287
Model 1	1.18 (1.04–1.35)	1.26 (1.07–1.49)	362/658	1.04 (0.81–1.34)	148/267
Model 2	1.26 (1.07–1.49)	1.25 (1.05–1.48)	335/571	1.33 (0.71–2.50)	68/112
Model 3	1.11 (0.91–1.36)	1.08 (0.87–1.33)	317/524	1.33 (0.67–2.64)	66/107
z (ln) eGFRcystatin C
Univariable	0.83 (0.73–0.95)	0.95 (0.82–1.10)	367/678	0.56 (0.42–0.74)	154/287
Model 1	0.95 (0.82–1.10)	1.06 (0.90–1.25)	363/661	0.68 (0.50–0.93)	148/267
Model 2	0.99 (0.83–1.18)	1.04 (0.86–1.25)	336/573	0.58 (0.32–1.05)	68/112
Model 3	0.99 (0.82–1.20)	1.02 (0.83–1.25)	318/526	0.69 (0.37–1.29)	66/107
z (ln) eGFRcystatin C/eGFRcreatinine
Univariable	0.82 (0.72–0.92)	0.90 (0.78–1.03)	366/675	0.60 (0.45–0.78)	154/287
Model 1	0.84 (0.73–0.96)	0.91 (0.78–1.06)	362/658	0.66 (0.49–0.88)	148/267
Model 2	0.84 (0.72–0.99)	0.88 (0.74–1.04)	335/571	0.58 (0.34–0.99)	68/112
Model 3	0.92 (0.77–1.09)	0.96 (0.79–1.15)	317/524	0.66 (0.38–1.16)	66/107

C/R: cases/referents; GFR: glomerular filtration rate; MI: myocardial infarction.

Model 1: Adjusted for plasma variables Apolipoprotein B/A1 ratio, ln CRP, and homocysteine (tHcy) quartiles.

Model 2: Model 1 + including systolic blood pressure (SBP), body mass index (BMI), and diabetes (yes/no).

Model 3: Model 2 + including smoking (present or past/never).

tHcy quartiles were for men, 8.98, 10.51, 12.22, and women 8.13, 9.42, 11.52 µmol/L. Odds ratios with p-values ≤.05 are shown in bold.

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Data availability statement

Aggregate data are included in the manuscript and its Supporting Information files. Individual data is not publicly available, as it contains potentially identifying patient information. Data are available upon request from the Northern Sweden Health and Disease Study Biobank. To request data, interested researchers must complete a formal application (available at https://www.umu.se/en/biobankresearch-unit/research/access-to-samples-anddata/access-to-nsdd/) and submit it to The Biobank Research Unit at Umeå University (contact via [email protected]).