Unfortunately, evaluation of only one or even two of the three biomarkers does not provide satisfactory information regarding the progressive state of CVD.
How can assessment of these three physiological parameters change the rules of the game? Historically, the focus has been on intervention at advanced, acute stages of the disease with far less emphasis on prevention or cost-effective screening of more precise early warning signals however, the ideal state remains detection at earlier phases of the atherosclerotic process and more effective monitoring of medical intervention to reduce the frequency of lifethreatening cardiovascular events. This undesirable situation does not meet the goal of reducing injury and death from CVD.
More sophisticated tests are not used routinely since most are invasive, involve radiation exposure, and have high cost. "Normal" levels for these risk factors are based on average population values and may not accurately assess individual risk or treatment efficacy. The primary monitoring tools for routine screening and management include clinical, blood, and urine tests that assess early risk factors such as blood pressure, hyperlipidemia, and diabetes. Although routine care is considered the first step in successfully reducing the number of CVD victims, it remains inadequate at all levels of injury severity, with the possible exception of very high-risk individuals who have a history of previous CV events. It thus seems reasonable to expect that ENDO, STIFF, and ANS should be monitored routinely, both to reduce the impact of their injury and as indicators of cardiovascular health and response to treatment. These two suggested mechanisms are supported by large body of clinical evidence. Their malfunction and the resulting contribution to increasing cardiovascular damage is thought to be caused by two mechanisms: (i) injury via other well-known CVD risk factors such as hypertension, hyperlipidemia, diabetes, chronic inflammation, and oxidative stress (the last two factors are considered the main triggers that initiate the atherosclerotic process) and (ii) injury of each of the three parameters by one another, compounding the damage. However, in the atherosclerotic process these three interdependent physiological parameters turn into major risk factors that enhance and accelerate the progression of atherosclerotic disease. Under normal conditions, endothelial function (ENDO), arterial stiffness (STIFF), and the autonomic nervous system (ANS) are involved together with other physiological processes in balancing normal function of the cardiovascular system. Here we suggest that routine simultaneous measurement of these three biomarkers could be an 2 of 56 important tool in the preventative health care regimen, and that significant efforts should be devoted to achieve this target. Still, in contrast to their great potential, assessment of these three parameters is infrequent, limiting their contribution to routine care. Improving routine care is fundamental to reaching the important goal of reducing CVD injury, including both nonfatal and fatal events. A significant part of this review is therefore devoted to elucidating the involvement of arterial stiffness and autonomic nervous system malfunction in the atherosclerotic process and CVD, and their complementarity to endothelial malfunction. Thus, the concomitant assessment, in routine clinical practice, of the status of these three parameters, will provide improved evaluation of patients' CVD status and risk, and enable more effective guided treatment. These two biomarkers are also affected by a large number of CVD risk factors. While malfunction of the endothelium is widely accepted as a common pathway for known and even unknown CVD risk factors, much less attention has been given to two complementary parameters, arterial stiffness and autonomic nervous system malfunction. The authors thank Brian Berman, MSc, MBA, formerly a senior executive in drug discovery, for his long-term support and encouragement that ultimately led to this review Summary Background Cardiovascular diseases (CVD) and related conditions remain the leading cause of death in the developed world and many developing countries, imposing huge health related cost burdens of these economies.
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