Genetics of Hypertension and Heart Failure
Hypertension and heart failure are leading causes of death and disability worldwide. Both are complex multifactorial conditions with hypertension and heart failure at either ends of the cardiovascular continuum. Rare mutations resulting in monogenic forms
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Genetics of Hypertension and Heart Failure Sandosh Padmanabhan, Alisha Aman, and Anna F. Dominiczak
The high prevalence of hypertension (HTN) and its consequent significant adverse economic impact on the individual and population highlight the importance of understanding the causation of HTN and developing effective early primary prevention measures to interrupt and prevent the continuing and expensive cycle of managing HTN and its complications [1]. Heart failure (HF) is a leading cause of death worldwide [2] with HTN being one of its important risk factors. Both HTN and HF are complex multifactorial diseases involving multiple pathways affected by genetic predisposition, ageing process and environmental factors. HTN, cardiomyopathies and ischaemic heart diseases are among the biggest risk factors for causing HF, which are of two types—HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). In contrast to HFrEF, HFpEF which accounts for 50% of HF prevalence has many unique challenges including difficulty in diagnosis and lack of effective treatment [2]. For understanding and predicting HTN and HF, both individual life histories may be as important as population histories. Their genetic determinants can provide keys to the underlying mechanisms and lead to a better personalised diagnosis and therapy. In this chapter, we will describe the genetic
S. Padmanabhan · A. Aman Institute of Cardiovascular and Medical Sciences, Glasgow, UK e-mail: [email protected]; [email protected] A. F. Dominiczak (*) Institute of Cardiovascular and Medical Sciences, Glasgow, UK College of Medical, Veterinary and Life Sciences, University of Glasgow, Wolfson Medical School Building, Glasgow, UK e-mail: [email protected]; [email protected] © Springer Nature Switzerland AG 2019 M. Dorobantu et al. (eds.), Hypertension and Heart Failure, Updates in Hypertension and Cardiovascular Protection, https://doi.org/10.1007/978-3-319-93320-7_2
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underpinnings of HTN and HF—while both these conditions have different genetic predictors, the determinants of hypertension will have an impact on HF as part of the cardiovascular continuum [3]. The genetics of other causes of HF such as ischaemic heart disease is beyond the scope of this chapter.
2.1
Heritability of Hypertension and Heart Failure
Family studies have consistently demonstrated a genetic component influencing blood pressure (BP) as well as HF. The heritability of clinic systolic BP and diastolic BP is around 15–40% and 15–30%, respectively, whereas for ambulatory night-time systolic and diastolic BP, the heritabilities are 32–70% and 32–50% [4– 10]. The sibling recurrent risk (λs) of HTN is around 1.2–1.5 [11]. In an analysis of the Framingham Heart Study, the occurrence of HF in at least one parent (occurring before 75 years of age) was a significant predictor of the HF phenotype in the offspring (hazard ratio 1.70 [95% confidence interval (CI) 1.11–2.60 [12]]). Even after account
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