Aging associated cardiovascular changes and their relationship to heart failure

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aging associated cardiovascular changes and their relationship to heart failure

Aging represents a convergence of declining cardioprotective systems and increasing disease processes that is fertile ground for the development of heart. In the United States, cardiovascular disease, e.g., atherosclerosis and hypertension, that lead to heart failure and stroke, is the leading cause of mortality. However, many other changes that are common with aging are due to modifiable factors. If not treated, these can lead to heart disease. Older people on blood pressure medicines need to work with their doctor to find the Peripheral vascular disease, resulting in intermittent pain in the legs when walking.

A higher decrease in mean arterial pressure of older women in response to autonomic blockade as compared to younger women demonstrates the importance of the ANS in maintaining blood pressure in elderly individuals [ 62 ].

Reports have shown that age-related alterations in autonomic nerve activity reduced blood pressure, cerebral blood flow, bladder function, and heart rate variability HRV [ 546364 ].

HRV is an indicator of arrhythmic complications and strong predictor of mortality and sudden death [ 65 ]. The analysis of HRV provides vital information on the contributions of the ANS to the consecutive oscillations of heart rate [ 6366 ].

Nocturnal reduction in cardiac parasympathetic activity in elderly individuals elicits a decline in cardiovagal control [ 65 ]. Aging could disrupt ANS through reduction and increase in the input of parasympathetic and sympathetic nervous systems, respectively [ 67 — 69 ]. The parasympathetic and sympathetic imbalance decreases HRV [ 7071 ] which in turn promotes the incidence of cardiovascular events [ 67 ]. The high frequency index of parasympathetic modulation indicated a relationship between aging and decline in HRV.

The low frequency index of HRV has been associated with an increase in sympathetic modulation. The increase in heart rate combined with the HRV reduction contributes to the degeneration of cardiac autonomic function during aging [ 72 ]. Reports have linked CVDs to morbidity and mortality among postmenopausal and obese women years around the world [ 73 — 77 ].

Some studies have reported higher values of HRV in premenopausal women as compared to postmenopausal women of the same age group. The cardioprotective contributions of sex hormones in such women have been reported [ 7879 ].

According to Davy et al. Studies have shown higher prevalence age-dependent HRV reduction among men [ 72 ]. Earlier reports on epigenetic relevance in aging-induced CVDs suggested that an active lifestyle is important to the health of the elderly. Elderly people were considered to be prone to slower cardiac, metabolic, and autonomic response as compared to younger ones due to deceleration in vagal reactivation and impairment of cardiac autonomic modulation [ 81 ].

The deleterious effects of advanced age on autonomic regulation could be minimized by intensive exercise [ 8283 ]. Intensive exercise could increase muscle mass and strength without changes in cardiovascular function [ 82 ]. A physical training regime could improve physiological adaptations and autonomic function [ 84 ]. Although intensive exercise seems to be beneficial to older individuals, there are needs for further research that could lead to health-enhancing exercise programs designed.

The ANS abnormalities were thought to be a common underlying pathophysiology of CVDs such as hypertension and heart failure [ 85 ]. In this regard, the atrial fibrillation AF is the most frequent arrhythmia that was associated with the imbalance of sympathetic and parasympathetic drive to the heart.

Patients with AF had reduction in cardiac performance due to the loss of the atrial contraction and ventricular disorder. The incidence of AF increases dramatically during aging [ 8687 ]. The surgical ablation which involves various degrees of denervation of ANS has been shown to be efficient against AF [ 8889 ]. The experimental procedures that target autonomic imbalance in animal models and human studies of AF have been developed [ 90 ].

Studies using a high frequency for sympathetic-mimicking atrial stimulation [ 91 ] and radiofrequency ablation of the cardiac autonomic ganglion plexus were acclaimed to be a good procedure for the abolishment of AF [ 92 ].

Nevertheless, in human patients, studies of combined ganglion plexus destruction and pulmonary vein isolation by radiofrequency ablation promoted reasonable results in preventing AF [ 9394 ]. On the other hand, pulmonary vein isolation plus renal denervation improved the lifespan by 1 year when compared to pulmonary vein isolation alone [ 95 ]. Relevance of Epigenetics and Advanced Age in the Evolution of Cardiovascular Diseases Advanced biological age is often characterized by the accumulation of epigenetic changes that can be correlated with the appearance of CVDs [ 96 ].

Chronic stress is one of the major environmental factors responsible for epigenetic changes that affect the cardiovascular system. Evidence has shown that chronic stress promotes modification in the hypothalamic pituitary adrenal pathway [ 9798 ]. Previous work of Natt et al. Kim and Stansfield [ 99 ] inferred that changes in the patterns of acetylation and methylation of genes encoding MMPs were associated with the development of aorta aneurysms. These results support epigenetic mechanisms of aortic aneurysm.

In addition to aortic aneurysm, cardiomyopathy, a pathology marked by intrinsic myocardial weakness, contractile dysfunction, and congestive heart failure, is one of the main CVDs induced by poor nutrition and a sedentary lifestyle.

The development of cardiomyopathy has been associated with the appearance of mitochondrial cardiac polymerase dysfunction and an increase in the methylation of the cardiac DNA. The authors reported different methylation patterns between the hearts of old and young rats. The synthesis and excessive accumulation of extracellular matrix proteins towards healing of lesions in the heart muscle have been identified as one of the causes of heart failure.

MicroRNAs participate in the regulation of various genetic and epigenetic mechanisms. Structural or epigenetic modifications in these microRNAs have been linked with aging [ ].

Aging changes in the heart and blood vessels

Atherosclerosis Cardiovascular system disorder such as atherosclerosis is common among aged patients [ ]. Atherosclerosis is a multifactorial and progressive disease. Its etiology involves the accumulation of lipid, inflammatory cells, fibrosis elements, and plaque formation and deposition in the arterial walls [ — ]. The aging process could accelerate structural and compositional modifications observed in atherosclerosis.

Spatial increase in the vessels and intimal and medial layers thickening are among such modifications. In addition, the accumulation of an extracellular matrix rich in glycosaminoglycans, collagen, and elastin fibers in the vasculature has been attributed to aging [ ]. As reported in literature, endothelial cell injury and atherosclerosis clearly suggest the susceptibility of aged vessels to lesion [ — ].

Aging-associated cardiovascular changes and their relationship to heart failure

Previous experiments that compared old and young rabbits subjected to long period of hyperlipidemic diet showed that old rabbit arteries constantly develop fibroatheromatous plaques [ ]. The formation of plaques, cholesterol deposits atheroma with a fibrous cap sclerosischaracterized the inflammatory process of atherosclerosis.

The infiltration of subendothelial spaces of arteries by oxidized lipoprotein often initiated atherosclerosis [ ]. The vascular remodeling reinforces the characterization of aging vessels by thickening and loss of elasticity [ ].

The cellular changes in atherosclerosis disease could reduce the number of medial vascular smooth muscle cells and increase collagen deposition []. Some authors have addressed the implications of cellular senescence in the atherosclerosis process [ — ].

The cellular senescence could occur in two forms: The replicative one arises from DNA damage-induced telomere shortening.

Aging-Associated Cardiovascular Changes and Their Relationship to Heart Failure - EM|consulte

This damage could result from the high content of reactive oxygen species ROSoncogenes, and telomere [ ]. In addition, the pathogenesis of atherosclerosis also involves the recruitment of immune cells. At the site of a lesion with abnormal functioning of endothelium, leukocytes, vascular smooth muscles, and platelets constitute the atheroma.

As lipid peroxidation occurs, many molecules that control cell proliferation are released. Moreover, the endothelial cells recruit monocytes and macrophages through the release of colony-stimulating factors [ ]. The monocytes and macrophages scavenge potentially harmful compounds. However, the inflammatory factor released by these cells promotes extracellular matrix protein deposition and changes of vascular smooth muscle cells proliferation and migration [].

Some experimental models of atherosclerosis have associated nutrition to age-induced vascular changes [ ]. In these experiments, a modifiable diet that has beneficial effects on old vessels was used to target caloric restriction CR [ ]. CR has been reported as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis [ ]. Previous study had implicated nicotinamide adenine dinucleotide- NAD- dependent deacetylases and adenosine diphosphate-ribosyltransferases e.

According to Kitada et al. Hence, this molecule could be an important pharmacological target against atherosclerosis.

aging associated cardiovascular changes and their relationship to heart failure

A possible mechanism by which CR exerts such beneficial effect could involve the actions of sirtuins, particularly SIRT1. SIRT1 has been regarded as a longevity gene that protects cells against oxidative and genotoxic stress [ ]. The activation of SIRT1 could exert many physiological effects, including reduced apoptosis, enhanced mitochondrial biogenesis, the inhibition of inflammation, the regulation of glucose and lipid metabolism, and adaptations to cellular stresses such as hypoxia, endoplasmic reticulum ER stress, and oxidative stress [ ].

aging associated cardiovascular changes and their relationship to heart failure

Thus, SIRT1 may exert protective effects against vascular aging and atherosclerosis. In addition, earlier reports also indicated an overexpression of miRa and increased acetylated p53 levels in endothelial cells.

Taken together, these results suggest that miRa regulates endothelial senescence in part through decreases of SIRT1 [].

This role is essential for the biogenesis of high-density lipoprotein HDL and reversal of cholesterol transport from peripheral tissues to the liver. This result suggested that miR silencing could be a useful therapeutic strategy against atherosclerosis [ ].

Recent advances in cellular research have suggested new possibilities for the pharmacological treatment of atherosclerosis []. The use of antigens as vaccines [ ], immunosuppressors cyclosporine and sirolimusand anti-inflammatory drugs has been proposed for the treatment of atherosclerosis.

However, anti-inflammatory drugs such as Rofecoxib cyclooxygenase-2 inhibitorwhich may trigger cardiovascular problems [ ], require a cautious application in patients with CVDs [ ]. Hence, better therapies are still needed for atherosclerosis treatment. New anti-inflammatory agents are under development and it is hoped that they will be available in the future [ ]. Stroke Stroke is the second most frequent cause of death after ischemic heart in the developed countries [ ] and commonly occurs in individuals over 65 years [].

Stroke may be caused by brain cell damage and brain tissue ischemia due to the disruption of blood supply by a thrombus [ ]. It has been reported that the incidence of stroke increases with age [ ]. At midlife, neuronal atrophic and glial cell changes begin at the same time. These changes result in the degeneration of white matter. Aging-induced modifications of white matter can influence the susceptibility of axons to ischemia [ ]. The astrocytic, microglial hyperactivity and subsequent development of leukoaraiosis have been reported.

According to Koton et al. The increase in glutamate concentration can trigger an influx of calcium ions, excitotoxicity, and cell death [ ]. The brain microvasculature also suffers from the influence of the aging process.

The structural and functional degeneration of the blood-brain barrier BBB during aging could disrupt local perfusion []. The changes in pH, water content, and the accumulation of glutamate and lactate in brain interstitial fluid are associated with the reduction in cerebral blood flow CBF [ — ].

aging associated cardiovascular changes and their relationship to heart failure

Cerebral hypoperfusion can induce microcirculation disturbance and oligemia as well as cerebral endothelium loss devoid of ischemic injury []. Some experimental data have suggested that the modifications of white matter brain microvasculature could lead to leukoaraiosis [ — ]. Despite the fact that BBB has the ability to adjust to slight aging-related alterations, its permeability often increases []. Cerebral vessel alterations during aging may decrease cerebrovascular reservoirs and make the brain more prone to ischemic injury and vascular insufficiency [ ].

All these changes could result in an ischemic stroke and vascular cognitive deficiency in the elderly [ ]. Age-related alterations that lead to a dysfunctional phenotype [ ] suggest the primary effect of aging in the development of CVDs [ ]. The dysfunctional endothelial phenotype could induce hemodynamic changes in humans, nonhuman primates, and rodents [, ].

The arterial endothelium participates in vital autocrine and paracrine functions that regulate fluid state, blood-tissue exchange of molecules, vascularization, immune system response, and vascular resistance. The resistance arteries [ ] maintain a healthy vascular endothelium state through chemical mediators like pro- and antioxidants, vasodilators, vasoconstrictors, and pro- and anti-inflammatory molecules, among others. Aging can be associated with endothelial dysfunction or impaired endothelial-dependent dilation EDD.

Earlier, Widlansky et al. Thus, it could be assumed that vascular aging is critical to the development of age-related CVDs. Findings from studies involving vascular aging models have also demonstrated impaired EDD, permeability, angiogenesis, and fibrinolysis [ — ].

Risk factors, such as elevated blood pressure, LDL cholesterol, blood glucose, and sodium intake [ — ], can modulate the severity of endothelial dysfunction. The clearance of high postprandial glucose and lipids decreases with age []. In addition, studies that involved endothelial culture which reported physiological elevations in glucose and lipids corroborate the vascular aging phenotype [].

General Discussion and Perspective Although aging and CVDs fall into a broad field of research with several publications, it is very difficult to cover all the relevant literature on their probable mechanistic connections. The established link between aging and biological changes has greatly advanced our knowledge about diseases such as heart fibrosis, hypertrophy, atherosclerosis, ischemic injury, hypertension, myocardial infarction, and stroke.

The current review was narrowed down to the alterations at the organ heart or cardiac tissuescellular, molecular, and ANS levels in an attempt to connect the complexity of aging processes to the development of CVDs. Then, the vessels begin to collect together into larger and larger veins, which return blood to the heart. Watch this video about: The heart has a natural pacemaker system that controls the heartbeat.

Some of the pathways of this system may develop fibrous tissue and fat deposits. The natural pacemaker the SA node loses some of its cells. These changes may result in a slightly slower heart rate. A slight increase in the size of the heart, especially the left ventricle, is not uncommon. The heart wall thickens, so the amount of blood that the chamber can hold may actually decrease despite the increased overall heart size.

The heart may fill more slowly. Heart changes cause the ECG of a normal, healthy older person to be slightly different than the ECG of a healthy younger adult. Abnormal rhythms arrhythmiassuch as atrial fibrillationare more common in older people. They may be caused by heart disease. Normal changes in the heart include deposits of the "aging pigment," lipofuscin.

The heart muscle cells degenerate slightly. The valves inside the heart, which control the direction of blood flow, thicken and become stiffer. A heart murmur caused by valve stiffness is fairly common in older people.

Receptors called baroreceptors monitor the blood pressure and make changes to help maintain a fairly constant blood pressure when a person changes positions or is doing other activities.

Cardiovascular Disease and Heart Age

The baroreceptors become less sensitive with aging. This may explain why many older people have orthostatic hypotension, a condition in which the blood pressure falls when a person goes from lying or sitting to standing. This causes dizziness because there is less blood flow to the brain. The capillary walls thicken slightly. This may cause a slightly slower rate of exchange of nutrients and wastes.