Optimal low-density lipoprotein is 50 to 70 mg/dl
Lower is better and physiologically normal
James H. O'Keefe, Jr, MD*,*,
Loren Cordain, PhD ,
William H. Harris, PhD*,
Richard M. Moe, MD, PhD* and
Robert Vogel, MD
* Mid America Heart Institute, Cardiovascular Consultants, Kansas City, Missouri, USA
Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado, USA
University of Maryland, University of Maryland Hospital, Baltimore, Maryland, USA
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Figure 1 Total cholesterol levels for hunter-gatherers, wild primates, and wild mammals, generally range from about 70 to 140 mg/dl (corresponding to low-density lipoprotein levels of about 35 to 70 mg/dl [24,25]). The mean cholesterol levels of modern Westernized humans are almost twice these normal values (13).
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Figure 2 Atherosclerosis progression varies directly with low-density lipoprotein (LDL) cholesterol. This regression line indicates that atherosclerosis does not progress when LDL is 67 mg/dl or below (18–24). Data from randomized placebo-controlled trials using statins for preventing atherosclerosis progression (analysis for Fig. 2) or preventing coronary heart disease events in primary (analysis for Fig. 3) or secondary (analysis for Fig. 4) prevention were utilized for computation of the univariate regression lines correlating LDL with outcomes. Regression estimates, model R2, and p values for LDL effect were obtained from the unweighted regression lines. AT = atorvastatin; CCAIT = Canadian Coronary Atherosclerosis Intervention Trial; LCAS = Lipoprotein and Coronary Atherosclerosis Study; MAAS = Multicentre Anti-Atheroma Study; MARS = Monitored Atherosclerosis Regression Study; MLD = mean luminal diameter; P = placebo; PLAC = Pravastatin Limitation of Atherosclerosis in the Coronary Arteries study; PR = pravastatin; REGRESS = Regression Growth Evaluation Statin Study; REVERSAL = Reversal of Atherosclerosis with Aggressive Lipid Lowering; S = statin.
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Figure 3 Coronary heart disease (CHD) event rates in primary prevention trials (4 to 5 years duration) are directly proportional to the on-treatment low-density lipoprotein (LDL) cholesterol levels. The event rate is predicted to approach 0 at an LDL level of about 57 mg/dl (5–7). AFCAPS = Air Force Coronary Atherosclerosis Prevention Study; ASCOT = Anglo-Scandinavian Cardiac Outcome Trial; WOSCOPS = West Of Scotland Coronary Prevention Study. Other abbreviations as in Figure 2.
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Figure 4 Coronary heart disease (CHD) event rates in secondary prevention trials (5 years in duration except the PROVE-IT study, which was 2 years) were directly proportional to low-density lipoprotein (LDL) cholesterol levels. The event rate is predicted to approach 0 at LDL of 30 mg/dl (8–12). 4S = Scandinavian Simvastatin Survival Study; CARE = Cholesterol And Recurrent Events trial; HPS = Heart Protection Study; LIPID = Long-term Intervention with Pravastatin In Ischemic Disease trial; PROVE-IT = PRavastatin Or atorVastatin Evaluation and Infection Therapy trial. Other abbreviations as in Figure 2.
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Figure 5 The PRavastatin Or atorVastatin Evaluation and Infection Therapy (PROVE-IT) trial randomized over 4,000 patients either to high-dose atorvastatin (low-density lipoprotein [LDL] = 62 mg/dl) or pravastatin (LDL = 95 mg/dl) (12). A 16% reduction in the primary end point was noted in the atorvastatin-treated group.
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