Chapter 8
Heart Disease Prevention and Management
Multi-micronutrients, Diet, and Lifestyle Recommendations

Despite current preventive recommendations for changes in diet and lifestyle to reduce the risk of heart disease, this disease remains the number one cause of death in the USA. Therefore the proposed recommendations are not having expected results. If there are no significant changes in the current preventive recommendations, the projected annual incidence of heart disease may increase from 981,000 in 2010 to 1,234,000 in 2040, an increase of about 25 percent in 30 years. Deaths from this disease are projected to increase from 392,000 in 2010 to 610,000 in 2040, an increase of about 56 percent. In 2010, the total direct medical cost of heart disease was $273 billion. The indirect cost (in lost productivity) was estimated to be about $172 billion. In 2030, the direct cost would increase to $818 billion and indirect cost to $276 billion (an increase of about 61 percent). The projected increase of heart disease and its related costs makes it imperative that we develop an additional strategy for prevention. Here I describe a novel strategy for the prevention of heart disease using multiple micronutrients that would complement the current recommendations.

Recommendations for Secondary Prevention

Generally, individuals age fifty years or older develop one or more risk factors for heart disease. However, in some people, heart disease can develop earlier. The common risk factors include high levels of total cholesterol, LDL-cholesterol and triglycerides, low levels of HDL-cholesterol, increased plasma levels of C-reactive protein and homocysteine, and increased levels of markers of oxidative stress and chronic inflammation. Secondary prevention is recommended to those who have not had any major heart disease events--such as heart attack, atrial or ventricular fibrillation, or stroke--but who have developed one or more risk factors for heart disease as described above. Secondary prevention must include changes in diet and lifestyle, standard medications for lowering cholesterol and blood pressure, low-dose aspirin, and a micronutrient preparation containing multiple dietary and endogenous antioxidants.

Low-dose Aspirin
Low-dose aspirin at a dose of 81 mg per day is commonly recommended for reducing the risk and progression of heart disease because it prevents platelet aggregation by reducing the production of prostaglandins. Aspirin has been shown to reduce major cardiac or cerebral events by 25 percent. However, it has been reported that about 5-12 percent of patients with heart disease develop resistance to aspirin. Another study estimated that 8-45 percent of patients taking aspirin develop aspirin resistance. Furthermore, about 24 percent of patients taking aspirin show reduced response with respect to platelet aggregation (semi-responders). This has required physicians to increase aspirin doses in those patients who become semi-responders or develop aspirin resistance, until the toxic limit is reached. High doses of aspirin may cause bleeding. However, aspirin resistance continued to be present in some cases despite increased aspirin doses. It has been reported that the risk of major cardiac events may increase by about threefold in aspirin-resistant patients.

Although the mechanisms of aspirin resistance are not known, we suggest that the addition of multiple antioxidants may enhance the effectiveness of low-dose aspirin in reducing platelet aggregation. This is substantiated by the fact that vitamin E in combination with aspirin is more effective in inhibiting cyclooxygenase-1 (COX-1) enzyme activity than the individual agent. This enzyme is responsible for the production of prostaglandins that cause platelet aggregation. Thus, supplementation with multiple dietary and endogenous antioxidants may prolong the effectiveness of aspirin among semi-responders as well as in patients who develop total resistance to aspirin.

Micronutrient Supplements
Micronutrients containing dietary and endogenous antioxidants are equally important for secondary prevention, but they are not recommended by state or national agencies. Antioxidants are essential because they reduce both oxidative stress and chronic inflammation, which are important contributors to the development and progression of heart disease. The U.S. Prevention Service Task Force recommends multiple vitamin supplements to reduce the risk of cancer and heart disease. However, these recommendations do not provide guidelines with respect to the type of micronutrients that should be included. The doses and dose schedule were also not described. Our proposed micronutrient formulation for secondary prevention is shown in table 8.5 and is recommended to those who are fifty-one years or older with one or more risk factors for heart disease but who have not had any major heart disease-related events, such as myocardial infarction (MI) or stroke.

Low-dose aspirin is also important for reducing the aggregation of platelets. Therefore, the addition of proposed multiple micronutrients such as presented in the table 8.5 to the regimen of cholesterol and/or blood pressure-lowering drugs and low-dose aspirin appears to be one of the rational choices for the secondary prevention of heart disease.

Formulation for Adults Who Have One or More Risk Factors but Had No Major Heart Disease Events

Vitamin A (palmitate) -- 3,000 IU
Vitamin E (two forms) -- 400 IU / d-Alpha-tocopheryl succinate - 300 IU / d-Alpha-tocopheryl acetate - 100 IU
Vitamin C (calcium ascorbate) -- 1,500 mg
Vitamin D3 (cholecalciferol) -- 800 IU
Vitamin B1 (thiamine mononitrate) -- 4 mg
Vitamin B2 (riboflavin) -- 5 mg
Vitamin B3 (niacinamide ascorbate) -- 30 mg
Vitamin B6 (pyridoxine hydrochloride) -- 5 mg
Folic acid -- 800 mcg
Vitamin B12 (cyanocobalamln) -- 10 mcg
Biotin -- 200 mcg
Pantothenic acid (D-calcium pantothenate) -- 10 mg
Calcium citrate -- 250 mg
Magnesium citrate -- 125 mg
Zinc glycinate -- 15 mg
Selenium (seleno-L-methionine) -- 100 mcg
Chromium (as chromium picolinate) -- 50 mcg
N-acetylcysteine (NAC) -- proprietary dose
Coenzyme Q10 -- proprietary dose
Alpha lipoic acid -- proprietary dose
L-Carnitine -- proprietary dose
Omega-3 fatty acids -- proprietary dose
Natural mixed carotenoids -- proprietary dose

Total amount of proprietary dose antioxidants and herbal products is 1,440 mg.