Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis

Figures & data

Table 1. Characteristics at health survey.

	Referents/cases	Referents	Cases	p
Age at survey (years)	671/336	56.7 (56.0–57.3)	56.7 (55.8–57.6)	.94
Age at surgery (years)	–/336		67.2 (66.3–68.2)
Female sex (%)	671/336	48 (44–52)	48 (43–53)	.98
BMI (kg/m^2)	655/322	26.1 (25.8–26.4)	26.9 (26.4–27.4)	.01
Apolipoprotein B (g/L)^a	647/310	1.09 (1.07–1.11)	1.13 (1.10–1.16)	.05
Apolipoprotein A1 (g/L)^a	647/309	1.41 (1.40–1.43)	1.40 (1.37–1.42)	.25
Apolipoprotein B/A1 (ratio)^a	647/309	0.77 (0.76–0.79)	0.81 (0.78–0.84)	.01
Systolic blood pressure (mmHg)	545/270	135 (134–137)	138 (136–141)	.04
Diastolic blood pressure (mmHg)	545/269	84 (84–85)	86 (85–87)	.05
Total cholesterol (mmol/L)	535/265	6.2 (6.1–6.3)	6.4 (6.2–6.5)	.05
Hypertension (%)	545/269	49.2 (45.0–53.4)	61.0 (55.1–66.8)	.001
Glucose intolerance (%)	490/242	19.8 (16.3–23.3)	26.4 (20.8–32.0)	.05
Smoker (%)	531/258	53.7 (49.4–57.9)	59.7 (53.7–65.7)	.11
Creatinine (µmol/L)^a	647/310	73.2 (72.1–74.2)	72.3 (70.7–73.8)	.33
Cystatin C (mg/L)^a	647/309	0.84 (0.83–0.85)	0.85 (0.83–0.87)	.15
eGFRcreatinine (ml/min/1.73 m^2)^a	647/310	79.7 (78.8–80.6)	80.0 (78.6–81.5)	.66
Men		81.4 (80.2–82.6)	81.8 (79.9–83.7)	.76
Women		77.8 (76.5–79.2)	78.3 (76.2–80.5)	.68
No CAD		81.0 (79.6–82.5)	80.9 (78.5–83.2)	.89
CAD		78.8 (77.6–80.0)	79.4 (77.6–81.2)	.60
eGFRcystatin C (ml/min/1.73 m^2)^a	647/309	91.0 (89.6–92.4)	88.9 (86.6–91.4)	.15
Men		91.6 (89.7–93.5)	90.9 (87.6–94.3)	.74
Women		90.4 (88.3–92.5)	87.0 (83.6–90.5)	.09
No CAD		94.1 (91.8–96.5)	92.0 (88.2–96.0)	.34
CAD		89.0 (87.3–90.8)	86.8 (83.8–89.9)	.23
eGFRcystatin C/eGFRcreatinine (ratio)^a	647/309	1.14 (1.13–1.16)	1.11 (1.09–1.13)	.02
Men		1.12 (1.11–1.14)	1.11 (1.08–1.14)	.48
Women		1.16 (1.14–1.18)	1.11 (1.08–1.14)	.008
No CAD		1.16 (1.14–1.18)	1.14 (1.10–1.17)	.24
CAD		1.13 (1.11–1.15)	1.09 (1.06–1.12)	.04

BMI: body mass index; glucose intolerance: impaired fasting glucose and/or impaired glucose intolerance or diabetes mellitus; hypertension: systolic blood pressure ≥140 and/or diastolic blood pressure ≥90 and/or antihypertensive treatment; smoker: present or previous smoker.

Values shown are numbers, means (^ageometric), and proportions with 95% confidence intervals; p values were based on the Student t-test.

Bold values are p-value ≤ 0.05

Table 2. Creatinine and cystatin C and risk for future AVR.

		All			No CAD			CAD
	Ref/case	All	Men	Women	All	Men	Women	All	Men	Women
Creatinine
Q1	169/95	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00
Q2	174/81	0.81 (0.56–1.18)	1.17 (0.71–1.94)	0.53 (0.30–0.93)	0.77 (0.43–1.37)	1.21 (0.51–2.89)	0.53 (0.23–1.23)	0.86 (0.53–1.39)	1.16 (0.63–2.15)	0.52 (0.23–1.16)
Q3	165/65	0.68 (0.45–1.01)	0.86 (0.49–1.52)	0.53 (0.30–0.94)	0.84 (0.46–1.53)	0.98 (0.38–2.54)	0.83 (0.37–1.84)	0.58 (0.34–0.99)	0.80 (0.39–1.62)	0.35 (0.15–0.82)
Q4	139/69	0.85 (0.57–1.27)	0.83 (0.47–1.47)	0.83 (0.46–1.48)	1.09 (0.57–2.06)	0.77 (0.26–2.32)	1.29 (0.57–2.94)	0.75 (0.45–1.27)	0.90 (0.46–1.76)	0.53 (0.22–1.27)
Cystatin C
Q1	165/78	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00
Q2	161/66	0.88 (0.59–1.32)	0.92 (0.52–1.62)	0.85 (0.47–1.51)	0.82 (0.45–1.51)	0.77 (0.30–1.98)	0.87 (0.40–1.91)	0.92 (0.53–1.60)	1.04 (0.51–2.12)	0.79 (0.33–1.87)
Q3	160/72	1.02 (0.69–1.53)	1.00 (0.56–1.80)	1.05 (0.60–1.82)	1.14 (0.61–2.13)	1.16 (0.42–3.19)	1.10 (0.49–2.46)	0.94 (0.56–1.60)	0.92 (0.45–1.90)	0.99 (0.46–2.12)
Q4	161/93	1.32 (0.86–2.01)	1.43 (0.80–2.57)	1.21 (0.66–2.24)	1.19 (0.60–2.39)	1.76 (0.59–5.24)	0.92 (0.37–2.28)	1.42 (0.83–2.43)	1.38 (0.69–2.78)	1.53 (0.66–3.55)
eGFRcreatinine
Q1	162/79	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00
Q2	162/73	0.93 (0.62–1.40)	1.02 (0.55–1.87)	0.84 (0.48–1.47)	0.89 (0.45–1.76)	0.63 (0.19–2.06)	1.08 (0.46–2.54)	0.96 (0.57–1.59)	1.22 (0.60–2.50)	0.72 (0.34–1.53)
Q3	162/72	0.94 (0.62–1.42)	0.82 (0.45–1.49)	1.05 (0.58–1.91)	0.99 (0.51–1.94)	0.77 (0.25–2.38)	1.08 (0.46–2.50)	0.90 (0.52–1.53)	0.82 (0.40–1.67)	1.07 (0.46–2.50)
Q4	161/86	1.13 (0.73–1.73)	1.12 (0.62–2.05)	1.13 (0.60–2.12)	0.97 (0.49–1.90)	0.97 (0.33–2.87)	0.83 (0.34–2.02)	1.24 (0.70–2.19)	1.12 (0.53–2.36)	1.58 (0.63–3.98)
eGFRcystatin C
Q1	161/92	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00
Q2	162/66	0.72 (0.48–1.06)	0.56 (0.32–0.98)	0.91 (0.52–1.57)	0.96 (0.51–1.81)	0.49 (0.17–1.43)	1.42 (0.63–3.18)	0.58 (0.35–0.96)	0.54 (0.27–1.07)	0.61 (0.28–1.32)
Q3	163/77	0.78 (0.52–1.18)	0.85 (0.48–1.51)	0.71 (0.39–1.31)	0.84 (0.44–1.62)	0.67 (0.25–1.76)	1.02 (0.42–2.51)	0.75 (0.43–1.28)	0.90 (0.44–1.82)	0.54 (0.23–1.27)
Q4	161/74	0.74 (0.48–1.14)	0.65 (0.36–1.19)	0.85 (0.45–1.61)	0.85 (0.41–1.74)	0.46 (0.15–1.42)	1.31 (0.50–3.40)	0.67 (0.38–1.16)	0.72 (0.35–1.48)	0.59 (0.24–1.42)
Z (ln) creatinine	647/310	0.95 (0.83–1.08)	0.96 (0.80–1.16)	0.93 (0.77–1.13)	1.01 (0.81–1.26)	0.94 (0.66–1.35)	1.05 (0.80–1.39)	0.92 (0.78–1.10)	1.00 (0.80–1.24)	0.82 (0.62–1.10)
Z (ln) cystatin C	647/309	1.12 (0.97–1.29)	1.03 (0.85–1.25)	1.23 (1.00–1.51)	1.14 (0.91–1.43)	1.12 (0.77–1.65)	1.15 (0.87–1.53)	1.11 (0.93–1.33)	1.01 (0.81–1.26)	1.32 (0.98–1.78)
Z (ln) eGFRcreatinine	647/310	1.05 (0.90–1.23)	1.05 (0.84–1.30)	1.06 (0.85–1.32)	0.99 (0.77–1.27)	1.10 (0.71–1.70)	0.93 (0.68–1.27)	1.08 (0.89–1.31)	1.01 (0.79–1.29)	1.20 (0.86–1.68)
Z (ln) eGFRcystatin C	647/309	0.89 (0.77–1.02)	0.96 (0.79–1.17)	0.81 (0.65–1.00)	0.87 (0.69–1.11)	0.88 (0.59–1.31)	0.87 (0.65–1.16)	0.89 (0.74–1.07)	0.99 (0.78–1.24)	0.75 (0.55–1.02)

AVR: aortic valve replacement; CAD: coronary artery disease.

Values are the odds ratios with (95% confidence intervals) related to creatinine and cystatin C levels and corresponding estimated glomerular filtration rates (eGFR).

The risk related to quartiles (Q1–Q4) and 1 (ln) SD increase (Z-score) is shown. Z-scores with missing values replaced were used for all calculations. Fifty missing values for creatinine (and eGFR_creatinine) and 51 missing values for cystatin C (and eGFR_{cystatin C}) were replaced with the median values obtained for the referents (sex-specific).

Cut-offs for the quartiles (Q1–Q4) were: creatinine (µmol/L) (men and women): 75.6, 82.3, 88.5 and 71.5, 78.9, 86.7, respectively; cystatin C (mg/L) (men and women): 0.76, 0.83, 0.92 and 0.75, 0.83, 0.94, respectively. eGFR_creatinine (ml/min/1.73 m²) (men and women): 75.6, 82.3, 88.5 and 71.5,78.9, 86.7, respectively; and eGFR_{cystatin C} (ml/min/1.73 m²) (men and women): 82.5, 91.8, 103.5 and 78.6, 91.3, 104.4, respectively.

P values indicating a trend: .33 for creatinine, .24 for cystatin C, .66 for eGFR_creatinine, and .37 for eGFR_{cystatin C}.

Table 3. eGFR_{cystatin C}/eGFR_creatinine ratio and risk for future AVR.

		All			No CAD			CAD
Quartiles	Case/Ref	All	Men	Women	All	Men	Women	All	Men	Women
Q1	91/160	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00	1.00
Q2	85/163	0.91 (0.61–1.34)	0.98 (0.56–1.70)	0.84 (0.49–1.46)	1.26 (0.66–2.40)	1.91 (0.65–5.55)	1.00 (0.44–2.25)	0.72 (0.44–1.19)	0.72 (0.37–1.41)	0.72 (0.34–1.53)
Q3	71/162	0.75 (0.51–1.10)	0.79 (0.45–1.38)	0.70 (0.41–1.21)	0.76 (0.40–1.45)	0.81 (0.30–2.19)	0.75 (0.32–1.74)	0.77 (0.47–1.27)	0.86 (0.43–1.72)	0.70 (0.34–1.45)
Q4	62/162	0.62 (0.40–0.95)	0.73 (0.40–1.32)	0.52 (0.28–0.97)	0.79 (0.40–1.57)	0.64 (0.20–2.00)	0.90 (0.38–2.13)	0.53 (0.31–0.94)	0.82 (0.40–1.68)	0.26 (0.10–0.69)
Z (ln) ratio
Case/Ref		336/671	175/349	161/322	132/264	54/108	78/156	203/405	120/239	83/166
Univariable		0.84 (0.73–0.97)	0.93 (0.77–1.13)	0.74 (0.60–0.92)	0.86 (0.69–1.08)	0.85 (0.60–1.19)	0.87 (0.64–1.18)	0.83 (0.69–0.99)	0.99 (0.78–1.24)	0.65 (0.49–0.87)
Multivariable
Model 1		0.84 (0.73–0.97)	0.93 (0.76–1.13)	0.74 (0.60–0.92)	0.89 (0.70–1.13)	0.89 (0.62–1.28)	0.89 (0.65–1.23)	0.81 (0.67–0.97)	0.96 (0.75–1.23)	0.60 (0.44–0.83)
Model 2		0.85 (0.73–0.98)	0.94 (0.77–1.15)	0.75 (0.60–0.94)	0.92 (0.72–1.17)	0.96 (0.66–1.42)	0.89 (0.64–1.24)	0.80 (0.66–0.97)	0.96 (0.75–1.24)	0.56 (0.40–0.80)
Model 3		0.84 (0.73–0.98)	0.94 (0.77–1.15)	0.74 (0.60–0.93)	0.87 (0.68–1.11)	0.81 (0.56–1.19)	0.89 (0.64–1.24)	0.82 (0.68–0.99)	1.00 (0.77–1.29)	0.60 (0.43–0.84)
Model 4		0.80 (0.68–0.95)	0.93 (0.77–1.13)	0.53 (0.37–0.75)	0.77 (0.57–1.03)	0.89 (0.62–1.28)	0.52 (0.28–0.94)	0.81 (0.66–1.01)	0.96 (0.75–1.23)	0.47 (0.29–0.77)

AVR: aortic valve replacement; CAD: coronary artery disease.

Values are numbers and the odds ratios with (95% confidence intervals) for 1 (ln) SD increase (Z-score) in the eGFR_{cystatin C}/eGFR_creatinine ratio. Z-scores with missing values replaced were used for all calculations; 51 missing values were replaced with the median values obtained for the referents (sex-specific).

Cut-offs for the quartiles (Q1–Q4, eGFR_{cystatin C}/eGFR_creatinine ratio) were (men and women): 1.02, 1.13, 1.25 and 1.03, 1.17, 1.30, respectively. P value indicating a trend was .03 for the ratio.

Model 1 includes, in addition to the eGFR_{cystatin C}/eGFR_creatinine ratio, apolipoprotein B/A1 ratio (Z-score), glucose intolerance (yes/no), hypertension (yes/no) and smoking (present or past/never). Model 2 includes model 1 plus BMI, and model 3 includes model 1 plus hsCRP. Model 4 is identical to model 1 but all individuals from the MSP survey were excluded.

Data availability

The datasets generated during the current study are not publicly available as the dataset contains identifiable patient data but are available from the corresponding author on reasonable request.