Heart-Brain Interaction

Ali Ahmed, MD, MPHWashington DC VA Medical Center

University of Alabama at Birminghamaliahmedmdmph@gmail.com 

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 Birminghamaliahmedmdmph@gmail.com 

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