Twenty questions on atherosclerosis
Of the various atherosclerotic risk factors, which one is an absolute prerequisite for development of atherosclerosis?
If the LDL cholesterol level is <100— and possibly it needs to be <80 mg/dL—the other previously mentioned risk factors in and of themselves are not associated with atherosclerosis. In other words, if the serum total cholesterol is 90 to 140 mg/dL, there is no evidence that cigarette smoking, systemic hypertension, diabetes mellitus, inactivity, or obesity produces atherosclerotic plaques. Hypercholesterolemia is the only direct atherosclerotic risk factor; the others are indirect. If, however, the total cholesterol level is >150 mg/dL and the LDL cholesterol is >100 mg/dL, the other risk factors clearly accelerate atherosclerosis.
Because it is infrequently a disease related to defective genetic makeup, we should all try to get our serum LDL cholesterol levels down to the point where atherosclerotic plaques do not form, and that level is clearly <100 mg/dL and maybe <70 or 80 mg/dL. My goal for both primary and secondary prevention is the same—namely, serum LDL cholesterol <100 mg/dL.
http://www.legacy.library.ucsf.edu/documentStore/h/i/p/hip07e00/Ship07e00.pdf
In summary, in my view there are not 10 atherosclrotic risk factors, there is only 1-and that is an elevated(> 150 mg/dl) serum total cholesterol level and specifically an elevated serum LDL-cholesterol level. A low (<35 mg/dl) HDL-cholesterol level in the presence of an elevated LDL-cholesterol level probably should be viewed as an additive atherosclerotic risk factor. Male sex, family history of coronary events before age 55 in a parent or sibling, cigarette smoking, systemic hypertension, diabetes mellitus, and severe obesity are best viewed as cholesterol-dependent atherosclerotic risk factors and not in themselves atherogenic in the absence of a serum total cholesterol level > 150 mg/dl. Atherosclerotic events (coronary, cerebrovascular and peripheral), although predictive of future atherosclerotic events, are not by definition true atherosclerotic risk factors and they should not be viewed as such. Nevertheless, all of the aforementioned cholesterol-dependent atherosclerotic risk factors take effect when the serum total cholesterol level is > 150 mg/dl, and because 95% of Americans >-~O years of age have total cholesterol levels > 150 mg/dl, these indirect risk factors need to be dealt with and managed accordingly
Facts and ideas from anywhere
This is not to say that cigarette smoking, elevated blood pressure, diabetes mellitus, obesity, and inactivity are not harmful—of course they are—but if the serum LDL cholesterol is <60 mg/dL or the serum total cholesterol is <150 mg/dL, there is no evidence (with extremely rare exceptions) in my view that these other “risk factors” cause atherosclerosis.
And, yes, some blood inflammatory markers are commonly elevated in persons with atherosclerotic events. But, many patients have atherosclerotic events when the high-sensitivity (hs) C-reactive protein (CRP) is normal (<1 mg/dL), and patients with the highest levels of hs-CRP (e.g., rheumatoid arthritis, systemic lupus erythematosus) have only a slightly higher frequency of atherosclerotic events than do others of similar age and sex with normal or near-normal hs-CRP levels. The same principle, however, does not apply to cholesterol. The patients with the highest serum levels of total and LDL cholesterol, namely those patients with homozygous familial hypercholesterolemia, have an incredibly high frequency of atherosclerotic events, and they have them at very young ages—teenage years. And patients with the next highest serum LDL cholesterol levels, namely those with heterozygous familial hypercholesterolemia, have atherosclerotic events often in their 30s and 40s.
Of two people of similar age and sex and similar serum LDL cholesterol levels, say 130 mg/dL, the patient whose systolic systemic blood pressure is 170 mm Hg versus the other patient with a systolic pressure of 115 mm Hg is at much greater risk of an atherosclerotic event. And cigarette smoking may work in a similar fashion. Nevertheless, if the serum LDL cholesterol is <60 mg/dL, maybe <50 mg/dL, irrespective of the degree of blood pressure elevation or the number of cigarettes smoked daily, atherosclerotic plaques do not develop.
It is time to move on from a goal “to decrease risk” to a goal “to prevent plaques”. To do so requires much lower levels of LDL cholesterol than advocated by the guideline publications. My goal for all individuals worldwide is a serum LDL cholesterol at least <100 mg/dL and ideally <60 mg/dL. The beauty of the JUPITER trial is that it dramatically demonstrates what incredible reductions in events can be produced in a short period of time (<2 years) by reducing the LDL cholesterol by 50% even when starting from a level considered by many to be normal (<130 mg). The mean level (108 mg/dL) might be considered “good” or even “great” by many physicians, but lowering it to 55 mg/dL (by rosuvastatin 20 mg/dL) decreased all events by >40%, indeed nearly 50%, including a reduction in stroke by 48%! This trial beautifully shows that we can drastically reduce or even prevent atherosclerotic events and expensive procedures by taking a single pill every day and do it safely. Most Americans will not reach the JUPITER treatment levels (LDL cholesterol 55 mg/dL) by diet alone. The statin drugs have been ingested by humans now for nearly 30 years, and their safety and thus benefit/risk ratio may be the best of any proven useful medication. The toxicity resides mainly in atherosclerosis, not in the drug.
Have a healthy and happy Thanksgiving
Overload at the moment. But thank you, and Happy Thanksgiving to you and your family.
