Despite this, there are clear risk factors that contribute to the development of HFpEF.Hypertension, obesity, metabolic syndrome, and sedentary lifestyle have been identified as important risk factors for diverse types of heart disease including HFpEF. There is mechanistic and epidemiological evidence for a link between insulin resistance and HFpEF.This pro-inflammatory state may also induce changes in the vascular endothelium of the heart. Specifically, by reducing availability of nitric oxide, an important vasodilator and regulator of protein kinase G activity. As protein kinase G activity diminishes, cardiomyocytes undergo hypertrophic changes. Endothelial cells also are responsible for the production of E-selectin, which recruits lymphocytes into the tissue beneath the endothelium that subsequently release transforming growth factor beta, encouraging fibrosis and thus ventricular stiffening. Cardiac macrophages are thought to play an important role in the development of fibrosis as they are increased in HFpEF and release pro-fibrotic cytokines, such as IL-10. Further investigation of the role of inflammation in HFpEF is needed. Hypertension
Conditions, such as hypertension, that encourage increased left ventricular afterload can lead to structural changes in the heart on a gross, as well as a microscopic level. It is thought that increased pressure, in concert with a pro-inflammatory state (insulin resistance, obesity), encourage ventricular stiffening and remodeling that lead to poor cardiac output seen in HFpEF. There changes are a result of left ventricular muscle hypertrophy caused by the high pressure, leading to the left ventricle becoming stiff. Ischemia
Ischemia, or inadequate oxygenation of the myocardium, is observed in a high proportion of HFpEF patients.
It also adds to the development of the cornified cell envelope of keratinocytes. Its symptoms include excessive wrinkling of palmar skin, skin erosion, hyperpigmentation of the skin, ichthyosis, and allergy. Peeling skin syndrome 3
Peeling skin syndrome 3 is caused by a genetic defect in the carbohydrate sulfotransferase (CHST8) gene. This gene is characterized by a way of asymptomatic lifelong and non-stop dropping of the stratum corneum of the dermis. Its symptoms begin for the duration of the second half of the primary decade of existence and encompass generalized white scaling taking place over the upper and lower extremities. Peeling skin syndrome 4
Peeling skin syndrome 4 is caused by a genetic defect in the cystatin A (CSTA) gene. This gene is an intracellular thiol proteinase inhibitor. It has an essential role in desmosome-mediated cell-cellular adhesion inside the lower levels of the dermis. Its symptoms include well-circumcised peeling of skin on the extremities and neck, generalized dry skin with fine scaling and sparing of face, hyperkeratosis, and palmoplantar keratoderma

Peeling skin syndrome 5
Peeling skin syndrome 5 is caused by a genetic defect in the serpin (serpin family member 8) gene. This gene is produced by platelets and can bind to and inhibit the function of furin, which is a serine protease involved in platelet functions. It is also characterized by superficial peeling of the dorsal and palmar pores and skin of the hands and feet; the pores and skin of the forearms and legs may also be involved.