Epidemiology: Vascular biology, endothelial and vascular smooth muscle as well as cardiac dysfunction play a primary role in hypertension, cardio-vascular disease and target organ damage. Nutrient-gene interactions and epigenetics are predominant factors in promoting positive and negative effects in cardiovascular health and hypertension. In a series of research studies correlated to cardiovascular disease and hypertension, Dr. Mark C. Houston, MD, discussed the role that vascular biology and nutraceuticals play in relation to treatment of hypertension and cardiovascular disease.
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What is the cause of cardiovascular disease and hypertension?
Vascular disease can appropriately be described as the balance between vascular injury and vascular repair (Figure 1). The endothelium is strategically found to be closely associated to the bloodstream as well as the vascular smooth muscle and it is also in charge of discharging a variety of substances in order to preserve vascular homeostasis and health (Figures 2 and 3). Numerous irritations which can provoke damage or harm to the endothelium, can lead to endothelial dysfunction, or ED, and can cause hypertension and other cardiovascular diseases.
Hypertension might be a hemodynamic indication of a damaged or injuried endothelium and vascular smooth muscle which could be connected to definite inflammation responses, oxidative stress and immune dysfunction of the arteries leading to ED, vascular and cardiac smooth muscle disorder, loss of arterial elasticity together with reduced arterial compliance and increased systemic vascular resistance. Hypertension is a significant outcome of the interaction between environmental factors and genetics. Macronutrients and micronutrients are crucial in the regulation of blood pressure, or BP, following target organ damage, or TOD. Nutrient-gene interactions, subsequent gene expression, epigenetics, oxidative stress, inflammation and autoimmune vascular dysfunction have positive or negative influences on vascular biology in humans. Endothelial activation with endothelial dysfunction and vascular smooth muscle breakdown, or VSMD, can ultimately trigger and continue to stimulate the development and growth of hypertension.
Macronutrient and micronutrient deficiencies are extremely common in the general population and may be even more common in individuals with hypertension and cardiovascular disease associated with genetics, environmental factors and even prescription drug and medication usage. These deficiencies have an enormous impact on cardiovascular health issues, such as hypertension, myocardial infarction, or MI, stroke and renal disease. The diagnosis and treatment of those deficiencies will reduce BP and improve ED, vascular biology and health, as well as cardiovascular function.
Epidemiology, the branch of medicine that deals with the incidence, distribution, and possible control of diseases and other factors relating to health, emphasizes the role of diet and related nutritional intake when it comes to hypertension and cardiovascular disease. The transition from the Paleolithic diet to our modern diet has produced an outbreak of nutritionally-related diseases (Table 1). Hypertension, atherosclerosis, coronary heart disease, or CHD, MI, congestive heart failure, or CHF, cerebro-vascular accidents, or CVA, renal disease, type 2 diabetes mellitus, or T2DM, metabolic syndrome, or MS, and obesity are several examples of those diseases. Table 1 contrasts intake of nutrients included during the Paleolithic Era and modern time, involved in the regulation of blood pressure, or BP. An unnatural and unhealthy nutritional selection process has been established by evolution from a pre-agricultural, hunter-gatherer milieu into an agricultural, refrigeration society. In sum, diet has changed more than our genetics can adapt.
The human genetic makeup is approximately 99.9 percent that of our Paleolithic ancestors, however our nutritional, vitamin and mineral intakes have vastly changed. The macronutrient and micronutrient variations, oxidative stress from radical oxygen species, or ROS, and radical nitrogen species, or RNS, and inflammatory mediators, such as cell adhesion molecules, or CAMs, cytokines, signaling molecules and autoimmune vascular dysfunction of T cells and B cells, have contributed to the greatest prevalence of hypertension and other cardiovascular diseases through complex nutrient-gene interactions, epigenetic and nutrient-caveolae interactions and nutrient responses with pattern recognition receptors from the endothelium (Figure 4). A decrease in endothelin coupled with endothelial activation, increase in angiotensin II and nitric oxide bioavailability can cause coronary artery disease and vascular disease as well as hypertension. Poor nutrition, together with obesity and a sedentary lifestyle have led to an exponential increase in nutritionally-related ailments. In particular, the high Na+/K+ ratio of contemporary diets has contributed to hypertension, CVA, CHD, MI, CHF and renal disorder as have the relatively low intake of omega-3 PUFA, increase in omega-6 PUFA, saturated fat and trans fatty acids.
Vascular biology plays a major role in the initiation and perpetuation of hypertension. Oxidative stress (both ROS and RNS), inflammation and autoimmune vascular dysfunction (both T cells and B cells) are the primary pathophysiologic and functional mechanisms that cause cardiovascular disease (Figure 5). All three of them are closely interconnected and provide the absolute combination that leads to cardiovascular disease, or CVD, vascular smooth muscle and cardiac dysfunction, hypertension, vascular disease, atherosclerosis and endothelial dysfunction, or ED.
Hypertension is not a disease but is the proper and continuous, unregulated reaction with an exaggerated outcome of the infinite irritations to the blood vessel following environmental-genetic expression patterns and downstream disturbances in which the vascular system is the innocent bystander. This really becomes a maladaptive vascular response that was initially meant to provide vascular defense to the endothelial insults (Figure 6). Hypertension is a vasculopathy, characterized by ED, structural remodeling, vascular inflammation, improved stiffness, decreased distensibility and loss of elasticity. These insults are biomechanical (BP, heartbeat, blood circulation, oscillatory flow, turbu-lence, enhancement, pulse wave velocity and reflected waves) and biohumoral or biochemical which includes all the non-mechanical causes like metabolic, endocrine, nutritional, toxic, infectious and other etiologies.
In addition to the connections for endocrine and nutritional causes of hypertension, infections and toxins can increase blood pressure as well. Various toxins, such as mercury, polychlorinated biphenyls, lead, cadmium, arsenic and iron, also increase BP and CVD. Numerous microbial organisms have also been implicated in hypertension and CHD. All of these irritations lead to the altered vascular structure and function that manifests clinically as hypertension. Patients with hypertension have abnormal microvasculature in the form of inward eutrophic remodeling of the tiny resistance arteries leading to impaired vasodilatory capacity, increased cardiovascular disease, increased media to lumen ratio, decreased maximal organ perfusion and decreased flow reserve, particularly in the heart with decreased coronary flow reserve. Significant functional structural microvascular impairment occurs even before the individual’s blood pressure begins to increase in normotensive offspring of the patients with hypertension, as evidenced by endothelial dysfunction, diminished vasodilation, forearm vascular resistance, diastolic dysfunction, increased left ventricular mass index, increased septal and posterior wall thickness and left untreated hypertrophy. Therefore, the processes underlying the circulatory issues are associated to a vascular phenotype of hypertension that may be determined by early life programming and imprinting which may be compounded by cerebral aging.
In conclusion, vascular biology, endothelial and vascular smooth muscle as well as cardiac dysfunction play a primary role in hypertension, cardio-vascular disease and target organ damage. Then, the epidemiology, or the incidence, distribution, and possible control of diseases and other factors relating to health, emphasizes the role of diet and related nutritional intake when it comes to hypertension and cardiovascular disease. And finally, oxidative stress, inflammation and autoimmune vascular dysfunction are the primary pathophysiologic and functional mechanisms that cause cardiovascular disease. Hypertension is an indication of cardiovascular issues which should be addressed by a healthcare professional.
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By Dr. Alex Jimenez
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