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Heart-Brain Interaction
Ali Ahmed, MD, MPHWashington DC VA Medical Center
University of Alabama at [email protected]
Clinical Fundamentals of Multiple Organ Dysfunction
ESC HFA Congress Saturday, May 23, 2015
Seville, Spain
Chronic Conditions
• Conditions that – last a year or more – require ongoing medical attention and/or – limit activities of daily living
• Examples:– Physical: arthritis, cancer, CKD– Mental: depression, substance abuse, dementia
Multiple Chronic Conditions (MCC)
• 2 or more chronic conditions that affect a person at the same time.
• Examples: – arthritis and hypertension – heart disease and depression
Percentage of Medicare FFS Beneficiaries with the 15 Selected Chronic Conditions: 2010
Percentage of Medicare FFS Beneficiaries by Number of Chronic Conditions: 2010
Distribution of Medicare FFS Beneficiaries by Number of Chronic Conditions and Total Medicare
Hospital Readmissions: 2010
Percentage of Hospital Admissions with a Readmission within 30 days by Number of Chronic Conditions and
Age: 2010
Age-, sex-, race-adjusted association of multimorbidity with outcomes at 30-days of
follow-up in Medicare beneficiaries hospitalized for heart failure
45%22%8%
Prevalence of stroke
NEUROLOGY 2000;54:288–294
BMJ Open 2012;2:e000975. doi:10.1136/bmjopen-2012-000975
Model 1: adjusted for warfarin treatment, Model 2: also adjusted for sex, systolic blood pressure.
Incident heart failure (HF) and risk of subsequent stroke
Int J Cardiol. 2010; 144: 389–393
Am J Cardiol 2008;101:1772–1776
J Neurol (2008) 255:385–389
Stroke. 2009;40: 3706-3710
Assembly of Heart Failure Cohort in the Cardiovascular Health Study
Patients at risk for incident stroke (n=5448)
Community-dwelling adults, age ≥65 years (n=5795)
No baseline heart failure (n = 5219)
Baseline heart failure (n = 229)
Excluded: 347 (164 with baseline TIA and 183 with baseline stroke)
Assembly of Stroke Cohort in the Cardiovascular Health Study
Patients at risk of incident heart failure (n=5521)
Community-dwelling adults, age ≥65 years (n=5795)
No baseline stroke(n = 5307)
Baseline stroke(n = 214)
Excluded: 274 (baseline heart failure)
Baseline Characteristics
% or mean
Age, yearsFemaleAfrican AmericanMarriedLiving aloneEducation ≥college Income >$25KFair to poor healthCurrent smokerSmoking, pack-yearsAlcohol, units/week
Heart failureNo
n=5219Yes
n=229 P value
73 76 0.00159 54 0.13915 21 0.00667 54 <0.00113 18 0.02143 37 0.07738 21 <0.00122 64 <0.00112 10 0.33917 19 0.1963 1 0.005
StrokeNo
n=5307Yes
n=214 P value
73 75 <0.00158 48 <0.00115 26 <0.00167 64 0.34113 15 0.33343 42 0.66737 34 0.34623 45 <0.00112 13 0.83917 25 <0.0012.5 2 0.276
Baseline Medical History
% or mean
HypertensionCADAMIDiabetesPADCKDCOPDArthritis Cancer
Heart failureNo
n=5219Yes
n=229 P value
46 59 <0.00117 63 <0.0018 40 <0.001
15 31 <0.00112 27 <0.00120 36 <0.00112 21 <0.00152 62 0.00215 14 0.817
StrokeNo
n=5307Yes
n=214 P value
46 62 <0.00117 29 <0.0018 16 <0.001
15 26 <0.00112 30 <0.00120 39 <0.00112 16 0.07952 56 0.27015 13 0.449
Baseline Functional Data
% or mean
Social support scoreWalk last wk, blocksPhysical activity, kcalDepression scoreMMSE scoreBMI, kg/m2
Pulse, beats/minSBP, mmHgDBP, mmHg
Heart failureNo
n=5219Yes
n=229 P value
8.28 8.36 0.63640 26 <0.001
1669 1111 <0.0015 7 <0.001
28 27 <0.00126.6 27 0.10868 70 0.005
136.4 136.2 0.89471 67 <0.001
StrokeNo
n=5307Yes
n=214 P value
8.3 8.7 0.01840 35 0.242
1665 1273 0.0024.6 5.7 <0.001
27.6 26.2 <0.00126.6 26.3 0.34967.8 68 0.837136 142 <0.00171 72 0.245
Baseline Medications
% or mean
ACE inhibitorsBeta-blockersCCBsLoop diureticThiazide diureticDigoxinNitrateStatinAspirinNSAID’s
Heart failureNo
n=5219Yes
n=229 P value
6 28 <0.00112 14 0.61512 34 <0.0015 57 <0.001
11 6 0.0166 48 <0.0017 38 <0.0012 2 0.6563 8 <0.001
13 13 0.786
StrokeNo
n=5307Yes
n=214 P value
6 11 0.003
13 19 0.008
12 22 <0.001
5 8 0.010
11 14 0.298
6 13 <0.001
7 15 <0.001
2 2 0.898
3 10 <0.001
13 15 0.413
Baseline Laboratory Data
% or mean
Creatinine, mg/dlCholesterol, mg/dlLDL, mg/dlUric acid, mg/dlHemoglobin, g/dlWBC, 103/μLPlatelets, 103/μLFibrinogen, mg/dlCRP, mg/LInterleukin-6, pg/mlCoag factor VII, %
Heart failureNo
n=5219Yes
n=229 P value
0.95 1.2 <0.001212 197 <0.001130 118 <0.0015.6 6.6 <0.00114 13.5 <0.0016.3 6.7 <0.001251 237 0.007322 346 <0.001
5 8 <0.0012 3 <0.001
124 115 <0.001
StrokeNo
n=5307Yes
n=214 P value
0.95 1.2 <0.001212 211 0.747
130.3 129.7 0.7985.6 6.3 <0.00114 14 0.4636.3 7.0 <0.001251 252 0.861322 337 0.001
5 7 <0.0012.1 2.5 0.010124 121 0.235
Baseline ECG / Echo Data
% or mean
LVHAtrial fibrillationLBBBLVEF ≥55%
Heart failureNo
n=5219Yes
n=229 P value
4 14 <0.0013 15 <0.0018 28 <0.001
93 67 <0.001
StrokeNo
n=5307Yes
n=214 P value
4 8 0.0033 4 0.4898 14 0.003
93 89 0.034
Incident Stroke in Heart Failure
% (# of stroke / # at risk)No heart failure Heart failure
At 1 Year 1% (49/5219)
4% (10/229)
At 3 Years3% (168/5219)
8% (19/229)
At 13 Years14% (703/5219)
16% (37/229)
Incident Heart Failure in Stroke
% (# of HF / # at risk)No stroke Stroke
At 1 Year 1% (64/5307)
3% (6/214)
At 3 Years4% (219/5307)
10% (21/214)
At 13 Years20% (1077/5307)
29% (62/214)
Incident Stroke and Heart Failure
Stroke in HF
4%
8%
16%
At 1 Year
At 3 Years
At 13 Years
HF in Stroke
3%
10%
29%
1-Year Risk of Stroke and HF
HR (95% CI)
Unadjusted
Age-sex-race-adjusted
Multivariable-adjusted
Stroke in HF4.96
(2.51–9.79)
4.35 (2.18–8.66)
3.95 (1.67–9.35)
HF in Stroke
2.34 (1.01–5.41)
1.93 (0.83–4.48)
1.66 (0.71–3.91)
3-Year Risk of Stroke and HF
HR (95% CI)
Unadjusted
Age-sex-race-adjusted
Multivariable-adjusted
Stroke in HF3.04
(1.89–4.89)
2.43 (1.51–3.93)
1.51 (0.85–2.67)
HF in Stroke
2.53 (1.61–3.95)
2.12 (1.35–3.34)
1.69 (1.07–2.67)
13-Year Risk of Stroke and HF
HR (95% CI)UnadjustedAge-sex-race-adjustedMultivariable-adjusted
Stroke in HF1.97 (1.42–2.75)1.68 (1.21–2.35)1.23 (0.84–1.79)
HF in Stroke2.19 (1.69–2.83)1.87 (1.45–2.42)1.50 (1.16–1.94)
Age-Sex-Race-Adjusted Incidence of (1) Stroke in Heart Failure (HF) and (2) HF in Stroke,
During 13 Years of Follow-Up (CI=Confidence Interval)
Mortality by HF and Stroke
At 1 Year
At 3 Years
At 13 Years
HF (n=229)
10%
27%
75%
Stroke (n=160)
3%
13%
74%
Neither (n=5219)
1%
5%
43%
Both (n=23)
9%
30%
83%
Unadjusted Mortality by HF and Stroke
At 1 Year
At 3 Years
At 13 Years
HF (n=229)
8.4 (5.2–13.4)
5.8 (4.4–7.6)
3.0(1.2–1.6)
Stroke (n=160)
2.0(0.7–5.5)
2.4 (1.5–3.8)
2.7 (2.3–3.3)
Neither (n=5219)
1
1
1
Both (n=23)
7.0(1.7–28.4)
6.5 (3.1–13.8)
3.6 (2.3–5.7)
Age-Sex-Race-Adjusted Mortality by HF and Stroke
At 1 Year
At 3 Years
At 13 Years
HF (n=229)
6.7 (4.1–10.8)
4.6 (3.5–6.1)
2.4(2.1–2.8)
Stroke (n=160)
1.5(0.5–4.1)
1.9 (1.2–3.0)
2.3 (1.9–2.8)
Neither (n=5219)
1
1
1
Both (n=23)
4.5(1.1–18.6)
4.5 (2.1–9.6)
2.4 (1.5–3.8)
Age-Sex-Race-Adjusted All-Cause Mortality by Baseline
Heart Failure and Stroke During 13 Years of Follow-Up
(CI=Confidence Interval)
All-Cause Hospitalization by HF and Stroke
At 1 Year
At 3 Years
At 13 Years
HF (n=229)
39%
69%
93%
Stroke (n=160)
28%
58%
91%
Neither (n=5219)
16%
39%
83%
Both (n=23)
52%
91%
100%
Unadjusted All-Cause Hospitalization by HF and Stroke
At 1 Year
At 3 Years
At 13 Years
HF (n=229)
3.0 (2.4–3.7)
2.6 (2.2–3.1)
2.5 (2.1–2.8)
Stroke (n=160)
1.9(1.4–2.6)
1.8 (1.5–2.2)
1.7 (1.4–2.0)
Neither (n=5219)
1
1
1
Both (n=23)
4.5(2.6–8.0)
5.0 (3.3–7.7)
4.4 (2.9–6.7)
Age-Sex-Race-Adjusted All-Cause Hospitalization by HF and Stroke
At 1 Year
At 3 Years
At 13 Years
HF (n=229)
2.7 (2.2–3.4)
2.4(2.0–2.8)
2.2(1.9–2.5)
Stroke (n=160)
1.8(1.3–2.4)
1.6 (1.3–2.0)
1.5 (1.3–1.8)
Neither (n=5219)
1
1
1
Both (n=23)
3.9(2.2–6.9)
4.3 (2.8–6.7)
4.0 (2.6–6.0)
Conclusions
• In Community-dwelling older adults– Baseline heart failure is associated with higher risk
of incident stroke that attenuates with time– Baseline stroke is associate with higher risk of
incident heart failure that increases with time
• Both conditions are associated with higher mortality and hospitalization
Heart-Brain Interaction
Ali Ahmed, MD, MPHWashington DC VA Medical Center
University of Alabama at [email protected]
Clinical Fundamentals of Multiple Organ Dysfunction
ESC HFA Congress Saturday, May 23, 2015
Seville, Spain
Objective
• To examine the risk of heart failure in community-dwelling older adults with stroke
• To examine the risk of stroke in community-dwelling older adults with heart failure
• To examine the risk of mortality and hospitalization in community-dwelling older adults with heart failure and stroke
Cardiovascular Health Study (CHS)
• Deidentified public-use copy of the CHS data obtained from the NHLBI that also sponsored the study
• Ongoing, prospective population-based study of risk factors for the development and progression of cardiovascular disease in older adults
• 5888 Medicare-eligible community-dwelling adults ≥65 years from CA, MD, NC, and PA were recruited during 1989-1993
Exposures and Outcomes
• Baseline heart failure, free of baseline stroke– Outcome: incident stroke
• Baseline stroke, free of baseline heart failure– Outcome: incident heart failure
• Other Outcomes– Mortality and hospitalization – Follow-up: over 13 Years – All outcomes centrally adjudicated
Baseline Covariates
• Demographics:– age, sex, race, alcohol consumption
• Comorbidities:– hypertension, coronary artery disease, diabetes
mellitus, atrial fibrillation, stroke, chronic obstructive pulmonary disease, peripheral artery disease, cancer
• Laboratory data:– serum creatinine level, left ventricular
hypertrophy, left ventricular systolic dysfunction
Statistical Analysis
• Descriptive analyses • Multivariable Cox regression models were
constructed adjusting for baseline covariates• All statistical tests were two-tailed with 95%
confidence levels and p-values <0.05 were considered significant