Today's open access paper underscores the point that prevention and treatment of atherosclerosis should be a high priority in medical research, development, and practice. It is the single largest cause of death in our species, killing a quarter of humanity directly, and arguably another tenth indirectly. Atherosclerosis is the malfunction of macrophage cells responsible for clearing excess and altered cholesterol from blood vessel walls. The result is the accumulation of fatty lesions, and a tipping point in which the contents of the lesion overwhelm the macrophage cells attempting to remove it, thereafter continually adding dead cells to the growing atheroma. Blood vessels are narrowed, weakened, and inflamed. The inevitable rupture produces a stroke or heart attack. Along the way, reduced blood flow contributes to numerous other age-related conditions.
The authors here focus on prevention of atherosclerosis via lowered blood cholesterol. It is true that over a normal human life span, people with very low levels of blood cholesterol exhibit little atherosclerosis. Very low levels require treatments or mutation to achieve, but merely low levels can be attained through lifestyle choice. In such cases, the tipping point at which macrophages are overwhelmed is pushed out late enough that other forms of age-driven mortality are dominant in later life. If those other causes of death were dealt with, however, then sooner or later atherosclerosis would become a problem. Still, the epidemiology shows that the majority of the present pervasive mortality caused by atherosclerosis could in principle be avoided by suitable lifestyle choices. This is a frustrating state of affairs for clinicians, and that shows in the tone of the paper.
There is urgent need to treat atherosclerotic cardiovascular disease risk earlier, more intensively, and with greater precision: A review of current practice and recommendations for improved effectiveness
Atherosclerosis is the leading cause of disease, disability, and death in the United States and globally. Current medical practice has made progress, but agonizingly slowly considering the millions of people still adversely afflicted by atherosclerotic complications despite use of current treatments. This review examines how new approaches can significantly reduce the human cost of atherosclerosis. In light of the continued high rate of atherosclerotic disease, what seems needed is what Martin Luther King, Jr. called "the fierce urgency of now". An entire paradigm shift is required such that preventive efforts are embraced much earlier in life, as discussed later in the paper. We propose that preventing and controlling atherosclerosis, the greatest killer of both men and women, be the top priority of medical care in the United States.
While there has been a significant reduction in heart attack and stroke, large numbers of Americans still sustain myocardial and cerebral infarctions and other complications of atherosclerotic cardiovascular disease (ASCVD) Despite the wealth of evidence and the availability of effective preventive interventions, declines in ASCVD hit a nadir, and in fact, cardiovascular mortality has been on the rise over the last decade in both men and women in the US, and throughout the world. Even though modern technology has helped more victims of acute cardiovascular events survive, significant numbers of patients who survive due to stents and other interventions in the immediate acute phase nevertheless often experience long-term disability, reinfarction, and death secondary to inadequate treatment. Further, atherosclerosis causes or contributes to many other diseases besides coronary artery disease. Success cannot be claimed until they are equally addressed and reduced.
Current practices are certainly not eliminating atherosclerotic disease. Atherosclerotic disease is preventable since its drivers of risk are largely modifiable (e.g., hyperlipidemia, hypertension, diabetes, cigarette smoking, sedentary lifestyle, obesity). A more intensive, more precise approach applied earlier than is current practice has a higher likelihood of significantly reducing the total burden of atherosclerotic disease. Atherosclerosis represents a clinical paradox: it is potentially the most preventable or treatable chronic disease, yet it remains the greatest cause of disability and death throughout the world. This does not have to be the case.
There has been compelling and convincing justification for some time that an approach that includes keeping plasma atherogenic lipoproteins low from early in life will greatly reduce risk for ASCVD. The fact that animals, non-human primates, and humans who maintain low cholesterol levels from early in life have very little atherosclerosis all suggest that a 'normal' non-atherogenic LDL-C level is 20-40 mg/dl. That is of course difficult to achieve in a modern society, but may not in fact be necessary. The Tsimane tribe of Bolivia, for example, live unexposed to 'developed' life and are essentially free of atherosclerotic disease. The mean LDL-C and HDL-C in the Tsimane people are at 90 mg/dL and 39.5 mg/dL, respectively.