Many Factors Contribute to Vascular Disease
A 2010 analysis of the decline in CHD death rates from 1980 to 2000 highlighted the need to address multiple risk factors to protect against heart disease mortality. In this study, cholesterol reduction accounted for only a 34% decrease in mortality in individuals with heart disease. By comparison, the same paper estimated that reductions in systolic blood pressure were responsible for 53%, while smoking cessation accounted for 13%, and 5% was attributable to increased physical activity.40
In the Copenhagen Heart Study, which tracked 12,000 participants for 21 years, high cholesterol was the 6th most relevant risk factor for developing CHD in both men and women; diabetes, hypertension, smoking, physical inactivity, and no daily alcohol intake (light alcohol consumption is heart-healthy) presented larger risks for the disease.41 The controversial JUPITER trial, which examined prevention of CHD by statin drugs in persons with very low LDL cholesterol (but elevated highly-sensitive C-reactive protein [hs-CRP]) supported the conclusion that non-LDL cholesterol risk factors (such as inflammation) represent enough risk for CHD to warrant treatment, even if lipids are within low-risk ranges.42
In order to reduce risk, there must be a systematic approach and understanding of the multiple factors of cardiovascular risk and atherosclerosis. Optimal cholesterol management is important for risk reduction, but so is managing the several other established cardiovascular disease risk factors. Accordingly, efforts to lower cholesterol to mitigate cardiovascular risk should be paired with measures to reduce other risk factors such as inflammation, oxidation, hypertension, excess plasma glucose, excess body weight, excess fibrinogen, excess homocysteine, low vitamin K, insufficient vitamin D, hormone imbalance, etc.43 More information is available in Life Extension's Atherosclerosis and Cardiovascular Disease protocol.
High Blood Sugar Increases the Atherogenicity of LDL
Elevated levels of blood sugar create ideal conditions for glycation reactions to occur. Glycation is a process by which a protein or lipid is joined together non-enzymatically with a sugar. The resultant product is highly reactive and capable of damaging tissues it comes in contact with.
Glycation of LDL particles is a well-documented phenomenon that greatly increases the atherogenicity of LDL. Glycated LDL has been shown to be significantly more susceptible to oxidation than native LDL,44 and to substantially impair endothelial function.45 Also, glycated LDL stimulates oxidative stress and inflammation in vascular smooth muscle cells,46 which exacerbates plaque buildup within blood vessel walls. Glycated, oxidized LDL causes degradation of endothelial nitric oxide synthase (eNOS), an enzyme involved in maintaining proper vasodilatation and blood flow.47 Moreover, once LDL has become glycated it is no longer recognized by the LDL receptor on cell surfaces, meaning it will remain in circulation and is more likely to contribute to the atherosclerotic process.48,49
Individuals with diabetes are known to be at substantially greater risk for developing atherosclerosis than people with normal blood sugar; glycated LDL plays a major role in the increased cardiovascular disease prevalence in this population.48 Because the production of glycated LDL depends on the concentrations of sugars (particularly glucose and fructose) in the blood, maintaining healthy after-meal (≤125 mg/dL) and fasting (70‒85 mg/dL) glucose levels is an effective strategy for reducing heart disease risk.