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Hypertensive Heart Disease

Calvin Chin MD PhD

Senior Consultant and Clinician Scientist
National Heart Center Singapore

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 Outline
• Burden of hypertension

• Hypertensive heart disease – what it is and how to

assess

• Current management goals – any role for personalized

management?

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 • Franklin D Roosevelt died April 12,
1945: hemorrhagic occipital stroke
• Joseph Stalin died Feb 28, 1953:
hemorrhagic stroke
• Winston Churchill died Jan 24, 1965:
progressive ill health from previous
strokes

Prime Minister Churchill, President Roosevelt and Premier Stalin

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 “I have a terrible headache”

Unfinished portrait

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 Burden of Hypertension

• 2015: 874 million adults had HTN

• Annual estimated death rates:
1990: 98/100,000
2015: 106/100,000

30% of health loss occurred in

individuals with SBP 115-140mmHg

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Forouzanfar et. al. JAMA 2017;317:165

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 2010 2017 2020
Crude prevalence 19.8% 24.2% 35.5%
Age-standardized prevalence 19.8% 21.9% 31.7%
(2010 as reference population)

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 Current Treatment Targets for Hypertension

2017 ACC/AHA 2018 ESC

Start Treatment >130/80 >140/90

BP Goal (Office) <130/80 130-140/80-90*
IHD /HF <130/80 130-140/80-90*
CKD <130/80 130-140/80-90
DM <130/80 130-140/80-90*

*Lower than <130/80 in younger patients <65 years old

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 Blood pressure management is important
344,000 participants from 48 RCTs: 54% had previous CVD; 46% without previous CVD
Every 5mmHg CVD No CVD
Cardiovascular Disease No Cardiovascular Disease Reduction
MACE 0.89 0.91
(0.86-0.92) (0.89-0.94)
Stroke 0.89 0.85
(0.85-0.94) (0.80-0.90)
IHD 0.90 0.95
(0.88-0.95) (0.91-0.99)
HF 0.89 0.83
(0.83-0.95) (0.77-0.89)
CV death 0.98 0.93
(0.92-1.04) (0.88-0.98)

Lancet 2021;397:625
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 Restricted, Sensitive (Normal) Lancet 2021;397:625
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 Inherent Limitations
Sphygmomanometer
1896

• Diurnal variation
• Measurement variation – activities and mood
Up to 15mmHg variation has been
documented; leads to misclassification*
*Campbell 1994; McVicker 2001; Ripoles 2001; Carney 1999

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 “Same same but different”?

Patient 1 Patient 2 Patient 3

74 year old male 63 year old male 65 year old male
Hypertension for 15 years Hypertension 2 years Hypertension 7 years
(2 meds) (1 med) (1 med)
24H BP: 143/74 24H BP: 145/72 DM - Metformin
24H BP: 126/79

Management?
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 Hypertensive Heart Disease

Diez et al., Hypertension. 2010;55:1–8

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 Association Between LV mass and SBP

Goh et al., Circ Cardiovasc Imaging. 2017; 10:e006840

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 Assessment of HHD
Electrocardiogram Echocardiogram

• Provide early clues for LVH, associated • First line imaging in assessing hypertensive
structural/electrical abnormalities heart disease
• Lacks sensitivity and specificity • Assessing morphology and cardiac function
(systolic/diastolic)
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 Cardiovascular Magnetic Resonance and HHD

1. Accurate assessment of cardiac volumes 2. Tissue characterization – Fibrosis/Scarring

and function; Left ventricular mass

Kim et al. Circulation 1999;100:1992

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 LGE = Replacement Fibrosis (Irreversible)

Ischemic Pattern
(Infarction)

Non-Ischemic
Patterns

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 Cardiovascular Magnetic Resonance and HHD
Diffuse Fibrosis ECV Map (T1 Mapping)

“shades of grey” Quantitative

Chin, et al. JACC Cardiovasc Imaging. 2017 Nov;10(11):1320-1333

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 Myocardial Fibrosis in HHD

• Is it clinically important in patients with hypertension?

• If important, can it be modified?

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 Myocardial Fibrosis and Adverse Remodeling in HHD

P<0.001 P<0.001 P=0.02

150 50 300

High-sensitivity Troponin T, ng/L

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Indexed LV mass, g/m2

NT-proBNP, pg/mL
200
100 30

20
100
65
10
50 49 7.6 45.7
29.7
5.3
0 0

No Midwall Fibrosis Midwall Fibrosis No Midwall Fibrosis Midwall Fibrosis No Midwall Fibrosis Midwall Fibrosis
(n=216) (n=38) (n=216) (n=38) (n=216) (n=38)

Goh, Chin et al., Circ Cardiovasc Imaging. 2017; 10:e006840

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 Myocardial Fibrosis and Outcomes
786 patients with hypertension without cardiovascular diseases; follow-up 39 months

Iyer, Chin, et al. Hypertension 2022;79;1804

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 Circulation 2000;102:1388

Circulation 2002;105:2512

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 Impact of cardiometabolic diseases on cardiac remodeling

Hypertension

Diabetes
Mellitus

B Franjic, et al. Journal of Human Hypertension (2009) 23, 709–717

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 Myocardial Fibrosis in HTN/DM Patients
A. Inflammatory Response
Chemotaxis of leukocytes
Inflammatory response
Cell movement of dendritic cells
Chemotaxis of phagocytes
Chemotaxis of granulocytes
Immune response of leukocytes
Phagocytosis of cells
Recruitment of phagocytes
Influx of phagocytes
Phagocytosis of phagocytes
Recruitment of neutrophils
Phagocytosis of antigen presenting cells
Immune response of antigen presenting cells
Inflammation of absolute anatomical region
-3
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B. Immune Cell Trafficking
Homing of leukocytes
Chemotaxis of leukocytes
Cell movement of eosinophils
Cell movement of dendritic cells
Cell movement of dendritic cells
Chemotaxis of phagocytes
Cellular infiltration by lymphocytes
Leukocyte migration
Cell movement of leukocytes
Chemotaxis of granulocytes
Cellular infiltration by mononuclear leukocytes
Homing of mononuclear leukocytes
Cell movement of antigen presenting cells
Recruitment of mononuclear leukocytes
Recruitment of leukocytes
Recruitment of phagocytes
Influx of phagocytes
Recruitment of neutrophils
Influx of leukocytes
Recruitment of granulocytes
Adhesion of mononuclear leukocytes
-2 -1 0 1 2 3 -3 -2 -1 0 1 2 3
Z Score Z Score
HTN + Fibrosis HTN/T2DM + Fibrosis
Pua, Chin et al., Circ Cardiovasc Imag. 2023;16(7):545
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 “Same same but different”?
Patient 1 Patient 2 Patient 3
74 year old male 63 year old male 65 year old male
Hypertension for 15 years Hypertension 2 years Hypertension 7 years
(2 meds) (1 med) (1 med)
24H BP: 143/74 24H BP: 145/72 DM - Metformin
24H BP: 126/79
Normal cardiac function/volumes Normal cardiac function/volumes Normal cardiac function/volumes
No LVH LVH No LVH
Interstitium expanded Interstitial volume normal

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 Conclusions

• Peripheral blood pressure measurement and treatment

remain important

• Cardiac remodeling in “hypertensive heart disease” is more

nuanced than expected

• Assessing the myocardium can potentially improve risk

stratification in patients with cardiometabolic risk factors

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 Role of ARNI in Ventricular Remodeling in Hypertensive LVH

• Angiotensin receptor-neprilysin inhibitor (ARNi) is a new class of drug that

blocks the RAAS and augments natriuretic peptides.

• Sacubitril/valsartan has shown superior benefits over conventional ARB or

ACEi monotherapy in terms of blood pressure lowering, clinical outcome
improvement

• Pre-clinical data has suggested that sacubitril/valsartan has superior

efficacy in promoting the regression of myocardial fibrosis compared to
valsartan alone in HF with diabetes

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 Lee, Chin et al. Front Cardiovasc Med 2023 (NCT 03553810)

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 Altered Metabolism in the DM Heart

• Although diabetes mellitus is characterized by an apparent

abundance of substrate (free fatty acids and glucose), diabetic
myocardium uses almost exclusively free fatty acids for ATP
generation

• Mediated by an inhibition of pyruvate dehydrogenase (PDH)

• Resulting in reduced efficiency in ATP production

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 Hyperpolarized Magnetic Resonance

• Amplify MR signal intensity >104

• Imaging technology that will disrupt

PET to interrogate the entire
metabolic pathway without radiation

• Study cardiometabolic phenotypes

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 Physical
Activity
Inflammation

-omics Diabetes Lipids

Mellitus
Hypertension

Fatty Liver
Insulin Central
Resistance Obesity

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