Diverse mechanisms contribute to the development of<unk> , many of which are under-investigated and remain obscure. Despite this, there are clear risk factors that contribute to the development of<unk> . Hypertension, obesity, metabolic syndrome, and sedentary lifestyle have been identified as important risk factors for diverse types of<unk>  disease including<unk> . There is mechanistic and epidemiological evidence for a link between insulin resistance and<unk> . This pro-inflammatory state may also induce changes in the vascular endothelium of the<unk> . 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<unk>  and release pro-fibrotic cytokines, such as IL-10. Further investigation of the role of inflammation in<unk>  is needed. Hypertension Conditions, such as hypertension, that encourage increased left ventricular afterload can lead to structural changes in the<unk>  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<unk> . 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<unk>  patients. This ischemia may be secondary to coronary artery disease, or a result of the previously described changes in microvasculature. Ischemia can result in impaired relaxation of the<unk> ; when myocytes fail to relax appropriately, myosin cross bridges remain intact and generate tension throughout diastole and thus increase stress on the<unk> . This is termed partial persistent systole. Ischemia may manifest in distinct ways, either as a result of increasing tissue oxygen demand, or diminished ability of the<unk>  to supply oxygen to the tissue. The former is the result of stress, such as exercise, while the latter is the result of reduced coronary flow. Aging Cardiac senescence, or cellular deterioration that occurs as part of normal aging, closely resembles the manifestations of<unk> . Specifically, loss of cardiac reserve, diminished vascular compliance, and diastolic dysfunction are characteristic of both processes. It has been suggested that<unk>  merely represents an acceleration of a normal aging process. Senile systemic amyloidosis, resulting from accumulation of aggregated wild-type transthyretin as part of the degenerative aging process, is emerging as an important and underdiagnosed contributor to<unk>  with age. Other Any condition or process that leads to stiffening of the left ventricle can lead to diastolic dysfunction. Other causes of left ventricular stiffening include: * Aortic stenosis of any cause where the ventricular muscle becomes hypertrophied, and thence stiff, as a result of the increased pressure load placed on it by the stenosis. * Diabetes * Age – elderly patients mainly if they have hypertension. Causes of isolated right ventricular diastolic<unk>  are uncommon. These causes include: * Constrictive pericarditis * Restrictive cardiomyopathy, which includes Amyloidosis (most common restrictive), Sarcoidosis and fibrosis.
Heart failure with preserved ejection fraction
Ischemic cardiomyopathy
Diabetic cardiomyopathy
Hypertrophic cardiomyopathy
Dilated cardiomyopathy
Restrictive cardiomyopathy
Alcoholic cardiomyopathy
Amyloid cardiomyopathy