Untangling the Pathophysiologic Link Between Coronary Microvascular Dysfunction and Heart Failure With Preserved Ejection Fraction

Aish Sinha; Haseeb Rahman; Andrew Webb; Ajay M. Shah; Divaka Perera

Disclosures

Eur Heart J. 2021;42(43):4431-4441. 

In This Article

Clinical Links Between Coronary Microvascular Disease and Heart Failure With Preserved Ejection Fraction

Cardiovascular risk factors, such as hypertension, diabetes mellitus, hyperlipidaemia, and obesity, lead to a cascade of pro-inflammatory events that eventually lead to eNOS uncoupling and endothelial dysfunction. Hypertension has been implicated in the development of CMD.[38] In addition to causing eNOS dysfunction, it leads to enhanced endothelin production resulting in inappropriate coronary endothelial vasoconstriction.[39] Hypertension is also associated with architectural changes, such as capillary rarefaction, medial hypertrophy, and fibrosis of arteriolar vessels. These result in an inability of the coronary vasculature to augment its blood flow. Insulin resistance and hyperglycaemia, both cardinal features of diabetes mellitus, also alter coronary vascular tone regulation. Coronary microvascular disease is prevalent in patients with T2DM[22] and studies have shown that impaired myocardial flow reserve is strongly associated with the degree of albuminuria in these patients.[40] Coronary microvascular disease and albuminuria may, therefore, share common mechanisms related to the pathogenesis of diabetic micro-vasculopathy.

Women may be susceptible to coronary vasomotor disorders due to gender-specific risk factors, such as systemic inflammation and endocrine changes. During adulthood, men tend to have a higher inflammatory predisposition than women; however, this predilection swaps genders after menopause. Oestradiol is generally protective against inflammation and reduced oestrogen levels post-menopause are associated with altered vascular function, heightened systemic inflammation[41] and up-regulation of the renin–angiotensin–aldosterone and sympathetic nervous systems. These have all been implicated in the pathogenesis of CMD and HFpEF and serve as the reasons for why women may be biologically more likely to develop CMD–HFpEF.

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