Long-Term Risk of Stroke and Poststroke Outcomes in Patients with Heart Failure: Two Nationwide Studies

Figures & data

Table 1 Baseline Characteristics of People with and without Heart Failure Before Follow-Up

	No HF (N=73,492)		HF (N=18,373)		p
Sex	n	(%)	n	(%)	1.0000
Female	36,672	(49.9)	9168	(49.9)
Male	36,820	(50.1)	9205	(50.1)
Age, years					1.0000
30–39	1684	(2.3)	421	(2.3)
40–49	4480	(6.1)	1120	(6.1)
50–59	8156	(11.1)	2039	(11.1)
60–69	15,080	(20.5)	3770	(20.5)
70–79	24,880	(33.9)	6220	(33.9)
≥ 80	19,212	(26.1)	4803	(26.1)
Low income	2753	(3.8)	1254	(6.8)	<0.0001
Medical conditions
Hypertension	17,392	(23.7)	8759	(47.7)	<0.0001
COPD	4995	(6.8)	4128	(22.5)	<0.0001
Mental disorders	7438	(10.1)	3439	(18.7)	<0.0001
Diabetes	7322	(10.0)	4268	(23.2)	<0.0001
Atherosclerosis	1751	(2.4)	1867	(10.2)	<0.0001
Hyperlipidemia	2804	(3.8)	903	(4.9)	0.0017
Liver cirrhosis	1243	(1.7)	621	(3.4)	<0.0001
Renal dialysis	898	(1.2)	533	(2.9)	<0.0001
Parkinson’s disease					<0.0001
Number of hospitalizations	42,634	(58.0)	1820	(9.9)	<0.0001
0	11,197	(15.2)	3755	(20.4)
1	6510	(8.9)	2853	(15.5)
2	13,151	(17.9)	9945	(54.1)
≥ 3
Number of emergency visits	36,314	(49.4)	3462	(18.8)	<0.0001
0	11,706	(15.9)	3418	(18.6)
1	7716	(10.5)	2427	(13.2)
2	17,756	(24.2)	9066	(49.3)
≥ 3	17,756	(24.2)	9066	(49.3)
Use of anticoagulants	4235	(5.8)	5052	(27.5)	<0.0001
CHA2DS2-VASc score*					<0.0001
0	12,482	(17.0)	0	(0.0)
1	15,830	(21.5)	1512	(8.2)
2	30,187	(41.1)	3236	(17.6)
3	12,364	(16.8)	6142	(33.4)
4	2609	(3.6)	5975	(32.5)
≥5	20	(0.0)	1508	(8.2)

Note: *Time-varying assessments of CHA2DS2-VASc that was calculated at the end of follow-up period.

Abbreviations: COPD, chronic obstructive pulmonary disease; HF, heart failure.

Table 2 Long-Term Risk of Stroke for People with and without Heart Failure in the Overall and Stratified Analysis

	N	Events	Person-Years	Incidence*	HR	(95% CI)†
No heart failure	73,492	6336	596,129	10.6	1.00	(reference)
Heart failure	18,373	3211	137,217	23.4	1.82	(1.71–1.93)
Female
No heart failure	36,672	3008	301,688	9.97	1.00	(reference)
Heart failure	9168	1598	71,072	22.5	1.91	(1.75–2.08)
Male
No heart failure	36,820	3328	294,441	11.3	1.00	(reference)
Heart failure	9205	1613	66,145	24.4	1.75	(1.61–1.90)
Age, 30–49 years
No heart failure	6164	117	57,078	2.05	1.00	(reference)
Heart failure	1541	162	13,282	12.2	2.84	(1.95–4.14)
Age, 50–59 years
No heart failure	8156	382	70,689	5.40	1.00	(reference)
Heart failure	2039	302	16,335	18.5	2.70	(2.14–3.41)
Age, 60–69 years
No heart failure	15,080	1351	130,046	10.4	1.00	(reference)
Heart failure	3770	709	30,919	22.9	2.05	(1.81–2.33)
Age, 70–79 years
No heart failure	24,880	3051	197,202	15.5	1.00	(reference)
Heart failure	6220	1285	45,153	28.5	1.92	(1.75–2.10)
Age, ≥ 80 years
No heart failure	19,212	1435	141,115	10.2	1.00	(reference)
Heart failure	4803	753	31,528	23.9	1.13	(0.98–1.30)
0 medical condition
No heart failure	43,364	2202	361,932	6.08	1.00	(reference)
Heart failure	4151	589	34,035	17.3	2.05	(1.81–2.31)
1 medical condition
No heart failure	19,414	2413	155,028	15.6	1.00	(reference)
Heart failure	6904	1208	52,523	23.0	1.73	(1.59–1.90)
2 medical conditions
No heart failure	8012	1235	60,179	20.5	1.00	(reference)
Heart failure	4714	874	33,841	25.8	1.48	(1.32–1.66)
≥ 3 medical conditions
No heart failure	2702	486	18,990	25.6	1.00	(reference)
Heart failure	2604	540	16,817	32.1	1.62	(1.37–1.91)

Notes: *Per 1000 person-years. †Adjusted for all covariates listed in Tables 1 and S1.

Abbreviations: CI, confidence interval; HR, hazard ratio.

Table 3 Sensitivity Analyses for the Association Between Heart Failure and Stroke Risk

	N	Events	PYs	Incidence*	HR	(95% CI)†
Excluding stroke cases in 6 months
No HF	72,984	5828	596,009	9.78	1.00	(reference)
HF	17,807	2645	137,105	19.3	1.50	(1.40–1.60)
Excluding stroke cases in 12 months
No HF	72,520	5364	595,666	9.01	1.00	(reference)
HF	17,439	2277	136,835	16.6	1.31	(1.22–1.40)
Risk of ischemic stroke
No HF	68,873	1717	575,942	2.98	1.00	(reference)
HF	16,102	940	129,835	7.24	1.95	(1.74–2.18)
Risk of hemorrhagic stroke
No HF	67,629	473	570,560	0.83	1.00	(reference)
HF	15,383	221	127,458	1.73	1.91	(1.52–2.40)
Risk of other stroke subtypes
No HF	71,302	4146	586,824	7.07	1.00	(reference)
HF	17,212	2050	133,663	15.3	1.77	(1.64–1.91)
Non-HF cohort	73,492	6336	596,129	10.6	1.00	(reference)
HF cohort
injected diuretics	12,570	1788	93,662	19.1	1.47	(1.37–1.58)
injected cardiac stimulant	8202	649	60,892	10.7	0.80	(0.73–0.88)
HF patients without use of statins	12,995	2333	93,600	24.9	1.00	(reference)
HF patients with use of statins	5378	878	43,617	20.1	0.85	(0.78–0.93)
HF patients without use of metformin	16,426	2953	120,675	24.5	1.00	(reference)
HF patients with use of metformin	1947	258	16,542	15.6	0.64	(0.56–0.73)

Notes: Sensitivity test: HF was significantly associated with stroke risk after excluding cases developing stroke in the first 6 and 12 months after the onset of HF. *Per 1000 person-years. †Adjusted for all covariates listed in Tables 1 and S1.

Table 4 Characteristics of Hospitalized Stroke Patients with and without Heart Failure

	No HF (N=450,072)		HF (N=30,532)		p
Sex	n	(%)	n	(%)	<0.0001
Female	184,411	(41.0)	15,406	(50.5)
Male	265,661	(59.0)	15,126	(49.5)
Age, years					<0.0001
30–39	10,885	(2.4)	196	(0.6)
40–49	39,164	(8.7)	963	(3.2)
50–59	77,096	(17.1)	2388	(7.8)
60–69	110,684	(24.6)	5503	(18.0)
70–79	138,016	(30.7)	11,565	(37.9)
≥80	74,227	(16.5)	9917	(32.5)
Low income	27,059	(6.0)	2241	(7.3)	<0.0001
Medical conditions
Hypertension	210,270	(46.7)	17,770	(58.2)	<0.0001
Diabetes	104,825	(23.3)	9131	(29.9)	<0.0001
Hyperlipidemia	19,074	(4.2)	1273	(4.2)	0.5646
Atherosclerosis	9800	(2.2)	2160	(7.1)	<0.0001
Atrial fibrillation	5438	(1.2)	2620	(8.6)	<0.0001
COPD	43,329	(9.6)	8509	(27.9)	<0.0001
Liver cirrhosis	11,011	(2.5)	979	(3.2)	<0.0001
Renal dialysis	7466	(1.7)	1830	(6.0)	<0.0001
Parkinson’s disease	8345	(1.9)	806	(2.6)	<0.0001
Mental disorders	74,150	(16.5)	6933	(22.7)	<0.0001
Type of stroke					<0.0001
Hemorrhagic stroke	111,603	(24.8)	4798	(15.7)
Ischemic stroke	281,676	(62.6)	21,235	(69.6)
Other stroke	56,793	(12.6)	4499	(14.7)
Number of hospitalizations					<0.0001
0	343,022	(76.2)	10,479	(34.3)
1	67,635	(15.0)	8521	(27.9)
2	21,862	(4.9)	5057	(16.6)
≥3	17,553	(3.9)	6475	(21.2)
Number of emergency visits					<0.0001
0	266,457	(59.2)	10,752	(35.2)
1	109,655	(24.4)	7640	(25.0)
2	41,143	(9.1)	4794	(15.7)
≥3	32,817	(7.3)	7346	(24.1)
Use of antibiotics*	76,480	(17.0)	8860	(29.0)	<0.0001

Note: *Use of antibiotics within 3 months before stroke admission.

Abbreviations: COPD, chronic obstructive pulmonary disease; HF, heart failure.

Table 5 Outcomes of Stroke Patients with and without History of Heart Failure

Poststroke Outcomes	No HF (N=450,072)		HF (N=30,532)		Risk of Outcomes
	Events	(%)	Events	(%)	OR	(95% CI)†
Mortality	13,064	2.9	1267	4.2	1.40	(1.31–1.50)
Pneumonia	38,408	8.5	3951	12.9	1.33	(1.28–1.38)
Septicemia	17,212	3.8	2119	6.9	1.31	(1.24–1.38)
UTI	50,222	11.3	4249	13.9	1.02	(0.98–1.05)
ICU stay	92,062	20.5	7360	24.1	1.52	(1.47–1.57)
Medical expenditure, USD*	2232 ± 3470		2569 ± 3585		p<0.0001
Length of hospital stay, day*	11.6 ± 13.4		13.2 ± 13.7		p<0.0001

Notes: *Mean ± SD; HF was associated with medical expenditure (beta=331, p<0.0001) and length of hospital stay (beta=0.79, p<0.0001) in the multiple linear regressions. †Adjusted for all covariates listed in Table 4.

Abbreviations: CI, confidence interval; HF, heart failure; ICU, intensive care unit; OR, odds ratio; UTI, urinary tract infection.