Renal dysfunction increases the risk of ischemic and hemorrhagic stroke in the general population

Figures & data

Table I. Characteristics of study population in relation to glomerular filtration rates estimated by the Mayo formula.

		Estimated GFR (mL/min/1.73 m^2)
	All	>90	60–90	30–60	15–30
All individuals:	539,418	477,046	59,016	3,006	350
Percent of study population	100	88.4	10.9	0.56	0.07
Age (years)^a	44.7 (14.2)	42.1 (12.3)	64.5 (11.56)	72.5 (12.2)	67.3 (15.5)
Female sex (%)	46.7	44.5	64.1	49.3	39.1
Diabetes mellitus (%)^b	3.0	2.5	6.3	14.6	14.6
Estimated GFR (mL/min/1.73 m^2)^a	109.1 (16.9)	79.4 (11.4)	81.9 (6.8)	50.3 (7.7)	20.8 (6.7)
Laboratory values:
Glucose (mmol/L)^a	5.98 (1.26)	4.9 (1.2)	5.4 (1.7)	5.9 (2.7)	67.3 (15.5)
Total cholesterol (mmol/L)^a	5.57 (1.16)	5.5 (1.1)	6.2 (1.2)	6.2 (1.4)	6.1 (1.6)
Triglycerides (mmol/L)^a	1.32 (0.98)	1.29 (0.97)	1.53 (1.04)	1.93 (1.26)	2.06 (1.36)
Serum creatinine (µmol/L)^a	81.2 (14.5)	79.4 (11.4)	91.7 (15.2)	131.1 (19.6)	281.7 (146.0)

To convert total cholesterol to mg/dL, divide by 0.02586; to convert triglycerides to mg/dL divide by 0.01129; to convert glucose to mg/dL divide by 0.05551; and to convert serum creatinine to mg/dL divide by 88.4.

GFR = glomerular filtration rate.

^aAge, GFR, and all laboratory values are given as means with standard deviations.

^bIncludes individuals with fasting serum glucose >7.0 mmol/L (>126 mg/dL) or prior hospitalization for diabetes.

Table II. Hazard ratios of stroke with 95% confidence intervals in relation to glomerular filtration rate estimated by the Mayo formula.

	GFR-Mayo (mL/min/1.73 m^2)
	>90	60–90	30–60	15–30	Test for trend
Number of subjects	476,955	58,967	3,015	350
All strokes:
No. of strokes	10,782	6,299	549	48
Crude	1.00	5.38 (5.22–5.55)	15.1 (13.9–16.5)	14.4 (10.9–19.2)	P < 0.0001
Adjustment for age and sex	1.00	1.13 (1.09–1.18)	1.59 (1.45–1.76)	2.31 (1.74–3.08)	P < 0.0001
Multivariable adjustment^a	1.00	1.09 (1.05–1.14)	1.43 (1.30–1.57)	2.23 (1.65–2.96)	P < 0.0001
Ischemic stroke:
No. of strokes	7,685	4,751	384	36
Crude	1.00	5.68 (5.48–5.89)	14.9 (13.4–16.5)	15.5 (11.2–21.5)	P < 0.0001
Adjustment for age and sex	1.00	1.13 (1.08–1.19)	1.43 (1.28–1.59)	2.32 (1.67–3.23)	P < 0.0001
Multivariable adjustment^a	1.00	1.09 (1.04–1.14)	1.24 (1.10–1.39)	2.27 (1.63–3.17)	P < 0.0001
Hemorrhagic stroke:
No. of strokes	1,782	841	66	7
Crude	1.00	4.24 (3.91–4.61)	10.5 (8.20–13.4)	12.2 (5.78–25.5)	P < 0.0001
Adjustment for age and sex	1.00	1.06 (0.95–1.17)	1.35 (1.04–1.75)	2.33 (1.10–4.91)	P = 0.027
Multivariable adjustment^a	1.00	1.04 (0.93–1.15)	1.26 (0.96–1.64)	2.31 (1.10–4.87)	P = 0.095

GFR = glomerular filtration rate.

^aMultivariable adjustment was made for age, gender, diabetes mellitus, total cholesterol, and triglycerides.

Table III. Gender-specific hazard ratios of stroke with 95% confidence intervals in relation to glomerular filtration rate estimated by the Mayo formula.

	GFR-Mayo (mL/min/1.73 m^2)
	>90	60–90	30–60	15–30	Test for trend
Men
All strokes:
No. of strokes	7,574	2,266	263	22
Crude	1.00	4.10 (3.91–4.30)	11.1 (9.79–12.5)	8.35 (5.49–12.7)	P < 0.0001
Adjustment for age	1.00	1.08 (1.03–1.14)	1.51 (1.33–1.72)	1.65 (1.08–2.50)	P < 0.0001
Multivariable adjustment^a	1.00	1.05 (1.00–1.11)	1.44 (1.26–1.64)	1.62 (1.05–2.48)	P < 0.0001
Ischemic stroke:
No. of strokes	5,502	1,785	186	18
Crude	1.00	4.43 (4.20–4.67)	10.69 (9.23–12.4)	9.51 (5.99–15.1)	P < 0.0001
Adjusted for age	1.00	1.12 (1.06–1.19)	1.36 (1.16–1.58)	1.80 (1.13–2.86)	P < 0.0001
Multivariable adjustment^a	1.00	1.08 (1.02–1.15)	1.27 (1.08–1.49)	1.86 (1.17–2.96)	P < 0.0001
Hemorrhagic stroke:
No. of strokes	1,331	313	33	4
Crude	1.00	3.14 (2.78–3.55)	7.67 (5.43–10.83)	8.50 (3.19–22.6)	P < 0.0001
Adjustment for age	1.00	0.91 (0.80–1.04)	1.21 (0.85–1.73)	1.98 (0.74–5.28)	P = 0.75
Multivariable adjustment^a	1.00	0.88 (0.77–1.01)	1.16 (0.80–1.68)	1.98 (0.74–5.31)	P = 0.47
Women
All strokes:
No. of strokes	3,208	4,033	286	26
Crude	1.00	8.20 (7.83–8.59)	24.3 (21.5–27.4)	31.3 (21.3–46.1)	P < 0.0001
Adjustment for age	1.00	1.24 (1.16–1.33)	1.80 (1.57–2.07)	3.71 (2.51–5.49)	P < 0.0001
Multivariable adjustment^a	1.00	1.20 (1.12–1.28)	1.51 (1.31–1.74)	3.23 (2.17–4.82)	P < 0.0001
Ischemic stroke:
No. of strokes	2,183	2,966	198	18
Crude	1.00	8.86 (8.39–9.37)	25.1 (21.7–29.0)	33.0 (20.8–52.4)	P < 0.0001
Adjusted for age	1.00	1.17 (1.08–1.27)	1.54 (1.31–1.82)	3.31 (2.06–5.30)	P < 0.0001
Multivariable adjustment^a	1.00	1.12 (1.03–1.21)	1.23 (1.03–1.46)	2.87 (1.77–4.65)	P < 0.0003
Hemorrhagic stroke:
No. of strokes	451	528	33	3
Crude	1.00	7.41 (6.54–8.40)	18.4 (12.9–26.2)	23.5 (7.57–72.9)	P < 0.0001
Adjustment for age	1.00	1.39 (1.16–1.67)	1.86 (1.25–2.77)	3.64 (1.15–11.5)	P < 0.0001
Multivariable adjustment^a	1.00	1.38 (1.14–1.66)	1.70 (1.13–2.57)	3.46 (1.09–10.9)	P < 0.0001

GFR = glomerular filtration rate.

^a Multivariable adjustment was made for age, gender, diabetes mellitus, total cholesterol, and triglycerides.

Table IV. Adjusted hazard ratios for stroke in different age groups in relation to GFR estimated by the Mayo formula.^a

	GFR (mL/min/1.73 m^2)
All subjects (n = 539,287)	>90 HR	60–90 GFR-Mayo HR (95% CI)	30–60 GFR-Mayo HR (95% CI)	15–30 GFR-Mayo HR (95% CI)
All stroke:
(All ages)	1.0	1.09 (1.05–1.14)	1.43 (1.30–1.57)	2.23 (1.65–2.96)
30–65 yo (n = 11,138)	1.0	1.08 (1.02–1.14)	1.92 (1.52–2.41)	4.53 (2.81–7.29)
>65 yo (n = 6,067)	1.0	1.14 (1.06–1.22)	1.61 (1.43–1.81)	1.96 (1.34–2.83)
Ischemic stroke:
(All ages)	1.0	1.09 (1.04–1.14)	1.24 (1.10–1.39)	2.27 (1.63–3.17)
30–65 yo (n = 7,954)	1.0	1.08 (1.02–1.15)	1.82 (1.39–2.38)	4.69 (2.72–8.09)
>65 yo (n = 4,517)	1.0	1.17 (1.08–1.27)	1.53 (1.33–1.76)	2.19 (1.43–3.36)
Hemorrhagic stroke:
(All ages)	1.0	1.04 (0.93–1.15)	1.26 (0.96–1.64)	2.31 (1.10–4.87)
30–65 yo (n = 1,840)	1.0	0.99 (0.86–1.13)	2.63 (1.60–4.31)	4.49 (1.45–13.9)
>65 yo (n = 793)	1.0	1.13 (0.94–1.38)	1.41 (1.00–1.99)	2.17 (0.80–5.90)

CI = confidence intervals; HR = hazard ratios; GFR = glomerular filtration rate; yo = years old.

^aHazard ratios are presented with 95% confidence intervals after multivariable adjustment for age, gender, diabetes, total cholesterol, and triglycerides.

Appendix 1. Hazard ratios of stroke with 95% confidence intervals in relation to glomerular filtration rate estimated by the Modification of Diet in Renal Disease study equation.

	GFR-MDRD (mL/min/1.73 m^2)
	>90	60–90	30–60	15–30	P values
Number of subjects	203,524	316,732	18,684	347
All stroke:
No. of strokes	3,356	12,026	2,244	52
Crude	1.00	2.17 (2.09–2.25)	8.20 (7.77–8.65)	20.2 (15.4–26.5)	P < 0.0001
Adjusted for age and sex	1.00	0.96 (0.92–1.00)	1.22 (1.14–1.29)	2.40 (1.82–3.16)	P < 0.0001
Multivariable adjustment^a	1.00	0.94 (0.91–0.98)	1.12 (1.05–1.19)	1.86 (1.40–2.46)	P = 0.0039
Ischemic stroke:
No. of strokes	2,284	8,886	1,646	40
Crude	1.00	2.35 (2.24–9.36)	8.79 (8.25–9.36)	23.2 (16.6–31.7)	P < 0.0001
Adjusted for age and sex	1.00	1.02 (0.98–1.07)	1.24 (1.15–1.33)	2.60 (1.90–3.56)	P < 0.0001
Multivariable adjustment^a	1.00	0.99 (0.94–1.04)	1.11 (1.03–1.20)	1.92 (1.39–2.64)	P = 0.0038
Hemorrhagic stroke:
No. of strokes	604	1,811	273	8
Crude	1.00	1.80 (1.64–1.97)	5.38 (4.66–6.21)	16.4 (8.16–32.9)	P < 0.0001
Adjusted for age and sex	1.00	0.88 (0.80–0.97)	1.00 (0.85–1.18)	2.46 (1.22–4.96)	P = 0.57
Multivariable adjustment^a	1.00	0.88 (0.79–0.97)	0.98 (0.83–1.16)	2.20 (1.09–4.45)	P = 0.46

GFR = estimated glomerular filtration rate.

^aMultivariable adjustment was made for age, gender, diabetes mellitus, total cholesterol, and triglycerides. P values represent test for trend.

Appendix 2. Gender-specific hazard ratios of stroke with 95% confidence intervals in relation to glomerular filtration rate estimated by the Modification of Diet in Renal Disease study equation.^a

	eGFR (mL/min/1.73 m^2)
	>90	60–90	30–60	15–30	P value
Men
All strokes:
No. of strokes	2,633	6,831	642	19
Crude	1.0	2.32 (2.23–2.44)	11.3 (10.3–12.3)	12.2 (7.81–19.1)	P < 0.0001
Adjustment for age	1.00	0.97 (0.93–1.02)	1.36 (1.23–1.49)	1.78 (1.13–2.79)	P = 0.0020
Multivariable adjustment	1.00	0.95 (0.91–1.00)	1.24 (1.13–1.37)	1.73 (1.10–2.73)	P = 0.14
Ischemic stroke:
No. of strokes	1,825	5,165	485	16
Crude	1.0	2.54 (2.40–2.67)	12.2 (11.0–13.5)	14.9 (9.13–24.4)	P < 0.0001
Adjustment for age	1.0	1.03 (0.97–1.08)	1.36 (1.22–1.52)	2.07 (1.26–3.39)	P < 0.0001
Multivariable adjustment	1.0	0.99 (0.94–1.05)	1.22 (1.09–1.37)	2.02 (1.23–3.32)	P = 0.023
Hemorrhagic stroke:
No. of strokes	493	1,095	90	3
Crude	1.0	1.97 (1.77–2.19)	8.10 (6.47–10.14)	9.96 (3.20–31.0)	P < 0.0001
Adjustment for age	1.00	0.87 (0.78–0.97)	1.15 (0.91–1.47)	1.79 (0.57–5.58)	P = 0.38
Multivariable adjustment	1.00	0.88 (0.78–0.98)	1.12 (0.87–1.43)	1.78 (0.57–5.56)	P = 0.35
Women
All strokes:
No. of strokes	723	5,195	1,602	33
Crude	1.0	2.54 (2.35–2.74)	10.4 (9.5–11.4)	39.3 (27.7–55.7)	P < 0.0001
Adjustment for age	1.00	0.93 (0.86–1.00)	1.12 (1.02–1.24)	2.92 (2.06–4.16)	P < 0.0001
Multivariable adjustment	1.00	0.90 (0.83–0.98)	1.02 (0.93–1.13)	1.82 (1.26–2.63)	P = 0.019
Ischemic stroke:
No. of strokes	459	3,721	1,161	24
Crude	1.00	2.84 (2.58–3.13)	11.8 (10.6–13.1)	46.4 (30.8–69.9)	P < 0.0001
Adjustment for age	1.00	0.98 (0.89–1.09)	1.15 (1.02–1.29)	3.06 (2.02–4.64)	P < 0.0001
Multivariable adjustment	1.00	0.95 (0.86–1.05)	1.01 (0.90–1.14)	1.70 (1.10–2.63)	P = 0.17
Hemorrhagic stroke:
No. of strokes	111	716	183	5
Crude	1.00	2.28 (1.87–2.79)	7.60 (6.00–9.62)	35.6 (14.5–87.2)	P < 0.0001
Adjustment for age	1.00	0.89 (0.73–1.10)	0.94 (0.73–1.22)	3.16 (1.28–7.82)	P = 0.81
Multivariable adjustment	1.00	0.87 (0.71–1.07)	0.92 (0.71–1.20)	2.79 (1.12–6.96)	P = 0.93

eGFR = estimated glomerular filtration rate.

^aMultivariable adjustment was made for age, gender, diabetes mellitus, total cholesterol, and triglycerides. P values represent test for trend.