2017 Cardiovascular Disease Prevention SymposiumSeptember 2017
By Ben Best
The best way to prevent cardiovascular disease (atherosclerosis, high blood pressure, heart attack, stroke, etc.) is with a healthy lifestyle—eat healthy foods, exercise, don’t smoke, and don’t gain weight.
For many people this lifestyle is too difficult or troublesome. Physicians attempting to encourage this lifestyle are often not successful and must resort to drugs.
Drugs are usually effective in reducing blood pressure. Statin drugs lower LDL and total cholesterol. One in four Americans age 45 and over takes a statin.1
Blood plasma is 92% water. Water and oil don’t mix, so in order to transport fat in the bloodstream from the liver to body tissues, fats must be bound to lipoproteins. The two main forms of fat transported in the bloodstream by lipoproteins are triglycerides and cholesterol.
Two predominant lipoprotein particles are LDL (low density lipoprotein) and HDL (high density lipoprotein). Cholesterol attached to LDL (LDL cholesterol) is often called “bad cholesterol,” because the LDL particle can deposit the cholesterol behind blood vessel walls, causing atherosclerosis.
HDL cholesterol is called “good cholesterol” because the HDL particle transports cholesterol back to the liver. This classification is misleading because both LDL and HDL can be either beneficial or harmful, depending on particle size, oxidation, and other factors.
Statin drugs reduce plasma levels of LDL cholesterol by inhibiting cholesterol formation in the liver.
PCSK9 is a naturally occurring human enzyme that causes LDL receptors to be degraded. If PCSK9 activity is blocked, more LDL receptors will be present on cells to remove LDL cholesterol from the blood. This results in decreased levels of blood LDL cholesterol. (PCSK9 stands for “Proprotein Convertase Subtilisin Kexin9.”)
PCSK9 inhibitors are a new and expensive class of drugs that sharply reduce plasma LDL cholesterol.
Dr. Michael Ozner is a member of the Life Extension Scientific Advisory Board, a board certified cardiologist, and director of an annual symposium on preventing cardiovascular disease. This report concerns presentations made at his February 2017 symposium.
Michael Ozner, MD (medical director, Center for Prevention and Wellness, Baptist Health South Florida, Miami, Florida) as director of this symposium gave an overview of topics related to cardiovascular disease prevention. Dr. Ozner emphasizes the importance of a healthy lifestyle, noting that even in patients with high genetic risk for coronary artery disease, a healthy lifestyle can reduce that risk by half.2
Dr. Ozner is a firm believer in the benefits of the diet eaten in the region of the Mediterranean sea (one of his books is titled The Complete Mediterranean Diet). He mentioned a study of over 100,000 health professionals which found that replacing 5% of dietary saturated fat with either polyunsaturated fat, monounsaturated fat, or whole-grain carbohydrate reduced coronary heart disease risk by 25%, 15%, or 9%, respectively.3 Aerobic exercise can reduce plasma triglycerides by up to 20%.4
Concerning blood lipids, Dr. Ozner is very concerned about apolipoprotein B (apoB), which is the primary protein portion of all cholesterol particles other than HDL cholesterol.
High apoB is a better predictor of cardiovascular disease than high levels of LDL cholesterol.5 High apoB indicates numerous small, dense LDL cholesterol particles, the form of LDL which is most likely to be oxidized and cross blood vessel walls to cause atherosclerosis.6 High apoB in young adults predicts coronary artery calcification in midlife.7
Reduction of LDL cholesterol with statin drugs has been shown to reduce the incidence of heart attack and stroke.8,9 Using both a statin and anti-PCSK9 antibody is even more effective at lowering LDL cholesterol than statin alone.10,11
Triglycerides and Cardiovascular Disease
Peter Libby, MD (cardiovascular specialist, Brigham and Women’s Hospital, Boston, Massachusetts) spoke about the increasing levels of plasma triglycerides in Americans. Roughly a quarter of American adults have excessively high levels of blood triglycerides.12 Triglyceride-laden lipoprotein is an even greater cause of coronary heart disease than LDL cholesterol.13
Dr. Libby has noted that high HDL cholesterol tends to be associated with low plasma triglycerides, and vice versa.14 But when HDL is loaded with triglycerides, the HDL can become proinflammatory and cause atherosclerosis.14 High levels of triglycerides on any of the lipoproteins cause inflammation.15
Elevated triglycerides are associated with cardiovascular disease even in patients who have been successfully treated with statins.12 When type II diabetics have high triglycerides, they show greater coronary artery calcification (atherosclerosis).16
Potential Benefit of HDL Cholesterol
Sergio Fazio, MD, PhD (director of the Center for Preventive Cardiology at Oregon Health & Science University, Portland, Oregon) is concerned with the effects of HDL cholesterol on cardiovascular disease. Even among persons with low LDL cholesterol, those with the highest HDL cholesterol have less risk of cardiovascular disease than those with low HDL cholesterol.17 But while clinical trials have succeeded in raising HDL cholesterol in patients, this did not reduce cardiovascular disease risk.18,19
HDL cholesterol can become proinflammatory when LDL cholesterol is high.20 Another reason why raising HDL cholesterol was not effective may have been that there are different forms of HDL cholesterol, with some forms being more protective than others.21 HDL subclasses appear to have different functions. For example, small HDL particles appear to have the capacity to remove cholesterol from atherosclerotic plaques.22,23
A newly discovered compound known as CSL112 is capable of making HDL cholesterol particles smaller, and thereby more efficient at removing cholesterol from atherosclerotic plaques.24 CSL112 has not shown any harmful effects in clinical trials.
High Blood Pressure
William Cushman, MD (professor, Preventive Medicine, University of Tennessee, Memphis, Tennessee) is concerned with high blood pressure as a cause of cardiovascular disease.
Nearly one third of American adults have systolic blood pressure (when the heart contracts) greater than 140 mmHg and diastolic pressure (when the heart relaxes) greater than 90 mmHg.25
This high level (>140 mmHg systolic) of blood pressure raises the risk of coronary artery disease 44%, raises the risk of stroke 57%, raises the risk of heart failure 88%, and raises the risk of kidney failure 95%.26 A clinical study investigated whether persons having a systolic pressure above 130 mmHg would benefit from therapy to reduce systolic pressure to less than 120 mmHg. Three years after systolic blood pressure was lowered, death rates dropped by about 25%.27
Approximately a quarter of persons with high blood pressure (systolic pressure above 140 mmHg) cannot reduce their blood pressure with three medications (resistant hypertension).28 Most often, people with resistant hypertension are obese or elderly.
People with high blood pressure are more likely to have their blood pressure increased by salt consumption than people with normal blood pressure.29 Eating foods higher in potassium, such as fruits and vegetables (rather than cereals and meats) can lower blood pressure.30 The American Heart Association has estimated that increasing potassium consumption can decrease blood pressure and lengthen lifespan by several years.30
Life Extension® has long advocated optimal blood pressure in most people to be 115 mmHg systolic and 75 mmHg diastolic. Newer studies corroborate the benefits of having lower normal blood pressure readings.
Ian del Conde Pozzi, MD (cardiologist, West Kendall Baptist Hospital, Miami, Florida) spoke of the risk of stroke. More than 60% of patients with type II diabetes die of cardiovascular disease. But glucose control does not affect their risk of stroke.31 High blood pressure is the major risk factor for stroke.
A meta-analysis of 16 trials involving more than 70,000 patients showed that blood pressure-reducing medications lowered the incidence of stroke by 22%.32 Statin drugs were also shown beneficial. Clinical trials have shown that every 39 mg/dL decrease in LDL cholesterol resulted in a greater than 21% reduction of stroke risk33
Omega-3 Fatty Acids in Fish Oil
Carl Lavie, Jr., MD (cardiologist, Ochsner Medical Center, New Orleans, Louisiana) discussed how the omega-3 fatty acids found in fish oil can reduce cardiovascular disease.
Fish oil supplements have been shown to reduce inflammation and blood vessel constriction,34 while reducing irregular heartbeats (cardiac arrhythmias).35
Approximately a third of Americans have excessively high blood triglycerides.36 High blood triglycerides are a strong predictor of residual risk of cardiovascular disease in patients receiving maximal doses of statins.36
Omega-3 fatty acids reduce blood triglycerides significantly.37 The minimal effective dose is more than 2,000 mg of EPA/DHA from fish oil per day.37
Eskimos show prolonged bleeding times with their dietary consumption of 20 grams of omega-3 fatty acids per day, but Dr. Lavie has noted that doses of up to 7 grams per day do not cause prolonged bleeding.38 Consuming fish oil is safer than eating fish because toxic mercury attaches to fish meat, but is distilled out of quality omega-3 oil concentrates.38 One study showed that 4,000 mg of omega-3 fatty acids from fish oil reduce triglycerides by 45% in patients with high triglycerides.39
Paul Ziajka, MD, PhD (clinical assistant professor, Florida University School of Medicine, Orlando, Florida) spoke on the subject of lipoprotein(a) [Lp(a)], which is a highly atherosclerosis-causing particle attached to an LDL cholesterol particle. Patients with low LDL cholesterol nonetheless have a high cardiovascular disease risk if Lp(a) is high.40
Lp(a) has less resistance to oxidation than plain LDL cholesterol.41 Niacin has been used to lower Lp(a).42 Combining niacin with statin was effective in lowering Lp(a) while at the same time increasing HDL cholesterol.43
PCSK9 Action and Benefit
Peter Toth, MD, PhD (director, Preventive Cardiology, CGH Medical Center, Sterling, Illinois) discussed PCSK9 inhibition. Experiments with mice have confirmed that PCSK9 inhibition lowers LDL cholesterol.44 LDL cholesterol lowering with PCSK9 inhibition has also been shown in humans.45
PCSK9 has been shown to lower not only plasma LDL cholesterol but also triglycerides46 and Lp(a).47
A clinical trial demonstrated that adding PCSK9 inhibition to statin therapy results in additional reduction of LDL cholesterol as well as additional reduction of cardiovascular death and disease.48 PCSK9 inhibitors are much more expensive than statins, costing in excess of $1,000 per month.49
Coronary Artery Calcium
Khurram Nasir, MD (cardiologist, Baptist Health Medical Group, Miami Beach, Florida) is an advocate of testing for coronary artery calcium (CAC). This test uses high-speed radiological imaging to measure calcium in atherosclerotic plaques in the arteries of the heart. This helps determine the extent of coronary atherosclerosis.
Cardiovascular deaths and disease events are rare for persons who have no detectable CAC, mainly occurring in diabetics and former smokers.50 CAC is a more direct measurement of atherosclerosis than plasma LDL cholesterol or C-reactive protein, which are risk factors for atherosclerosis.51
More than one-quarter of American adults over age 40 take statin drugs.52 But Dr. Nasir has determined that people with no detectable CAC usually do not need to take a statin.53
Anthony Gonzalez, MD (chief of surgery, Baptist Hospital of Miami, Miami, Florida) discussed the benefits of gastric surgery for obese patients. Bariatric surgery reduces the size of the stomach, thereby reducing the amount of food a person can eat. Bariatric surgery substantially reduces cardiovascular death rates in obese patients54 and substantially reduces symptoms of type II diabetes.55
In 2010, gastric bypass was the most common form of bariatric surgery, but by 2013 sleeve gastrectomy had become the more common form.56
Sleeve gastrectomy is less technically difficult to perform, but gastric bypass produces better results. According to one study, gastric bypass reduced body weight 23%, reduced triglycerides 40%, and reduced insulin use by 35%. For sleeve gastrectomy, the reductions were 19%, 29%, and 34%, respectively.57 Earlier studies have shown similar results.58 In all cases, bariatric surgery produced far better results than could be obtained by intensive treatment with medications.57,58
Cholesterol is not a toxic substance. On the contrary, cholesterol is an essential component of all cell membranes. Steroid hormones (testosterone, estrogen, etc.), cortisol, bile acids, and vitamin D are synthesized from cholesterol. Cholesterol is so essential for mental function that nearly one fourth of the body’s cholesterol is in the brain, despite the fact that the brain accounts for only about 2% of total body weight.59,60 Suicidal patients typically have lower plasma cholesterol than nonsuicidal patients.61
LDL cholesterol becomes toxic when oxidized. Thus, smokers and other persons with high levels of oxidized LDL in their bloodstream are the main beneficiaries of cholesterol-lowering therapies. Considerable oxidation of LDL cholesterol occurs once it is behind blood vessels.62 Diabetes and chronic inflammation from other causes makes blood vessel walls more permeable to LDL and increases oxidative stress, thereby making LDL cholesterol more susceptible to oxidation.63,64
LDL is beneficial when it is transported from the liver to body tissues, as opposed to being deposited into the endothelium. HDL is “good cholesterol” because it attaches to oxidized cholesterol in LDL for transport back to the liver to be detoxified.65
Statins have cardiovascular benefits apart from LDL cholesterol lowering, including reduced inflammation.66
One of the most common side effects associated with statins (statin intolerance), is muscle pain. Statin intolerance, real or imagined, is usually seen as subjective complaints rather than objective measurable quantities.67 Especially in the elderly, muscle problems can be due to aging rather than statins. There are, nonetheless, objective problems seen with statin therapy, including an increased incidence of diabetes.68
Statins reduce the body’s synthesis of coenzyme Q10 and vitamin D. Statin intolerance could result from coenzyme Q10 depletion,69 L-carnitine deficiency,70 or vitamin D deficiency,71 all of which can be corrected with supplementation.
- Available at: http://www.health.harvard.edu/blog/statin-use-is-up-cholesterol-levels-are-down-are-americans-hearts-benefiting-201104151518. Accessed June 2, 2017.
- Khera AV, Emdin CA, Drake I, et al. Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. N Engl J Med. 2016;375(24):2349-58.
- Li Y, Hruby A, Bernstein AM, et al. Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease: A Prospective Cohort Study.J Am Coll Cardiol. 2015;66(14):1538-48.
- Watts GF, Ooi EM, Chan DC. Demystifying the management of hypertriglyceridaemia. Nat Rev Cardiol. 2013;10(11):648-61.
- Benn M, Nordestgaard BG, Jensen GB, et al. Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B: the Copenhagen City Heart Study. Arterioscler Thromb Vasc Biol. 2007;27(3):661-70.
- Lamarche B, Tchernof A, Moorjani S, et al. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Circulation. 1997;95(1):69-75.
- Wilkins JT, Li RC, Sniderman A, et al. Discordance Between Apolipoprotein B and LDL-Cholesterol in Young Adults Predicts Coronary Artery Calcification: The CARDIA Study. J Am Coll Cardiol. 2016;67(2):193-201.
- Cholesterol Treatment Trialists C, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-81.
- Toth PP, Thanassoulis G, Williams K, et al. The Risk-Benefit Paradigm vs the Causal Exposure Paradigm: LDL as a primary cause of vascular disease. J Clin Lipidol. 2014;8(6):594-605.
- Puri R, Nissen SE, Somaratne R, et al. Impact of PCSK9 inhibition on coronary atheroma progression: Rationale and design of Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV). Am Heart J. 2016;176:83-92.
- Gouni-Berthold I, Berthold HK. PCSK9 antibodies for the treatment of hypercholesterolemia. Nutrients. 2014;6(12):5517-33.
- Toth PP. Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease. Vasc Health Risk Manag. 2016;12:171-83.
- Rosenson RS, Davidson MH, Hirsh BJ, et al. Genetics and causality of triglyceride-rich lipoproteins in atherosclerotic cardiovascular disease. J Am Coll Cardiol. 2014;64(23):2525-40.
- Libby P. Triglycerides on the rise: should we swap seats on the seesaw? Eur Heart J. 2015;36(13):774-6.
- Nordestgaard BG. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology. Circ Res. 2016;118(4):547-63.
- Qamar A, Khetarpal SA, Khera AV, et al. Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics. Arterioscler Thromb Vasc Biol. 2015;35(8):1880-8.
- Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357(13):1301-10.
- Schwartz GG, Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367(22):2089-99.
- Khera AV, Rader DJ. Cholesterol efflux capacity: full steam ahead or a bump in the road? Arterioscler Thromb Vasc Biol. 2013;33(7):1449-51.
- Aryan Z, Noshad S, Afarideh M, et al. Comment on Sharif et al. HDL Cholesterol as a Residual Risk Factor for Vascular Events and All-Cause Mortality in Patients With Type 2 Diabetes. Diabetes Care 2016;39:1424-1430. Diabetes Care. 2016;39(10):e189.
- Williams PT, Feldman DE. Prospective study of coronary heart disease vs. HDL2, HDL3, and other lipoproteins in Gofman’s Livermore Cohort. Atherosclerosis. 2011;214(1):196-202.
- Anastasius M, Kockx M, Jessup W, et al. Cholesterol efflux capacity: An introduction for clinicians. Am Heart J. 2016;180:54-63.
- Fazio S, Pamir N. HDL Particle Size and Functional Heterogeneity. Circ Res. 2016;119(6):704-7.
- Didichenko SA, Navdaev AV, Cukier AM, et al. Enhanced HDL Functionality in Small HDL Species Produced Upon Remodeling of HDL by Reconstituted HDL, CSL112: Effects on Cholesterol Efflux, Anti-Inflammatory and Antioxidative Activity. Circ Res. 2016;119(6):751-63.
- Cushman WC, Ford CE, Einhorn PT, et al. Blood pressure control by drug group in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens (Greenwich). 2008;10(10):751-60.
- Muntner P, Davis BR, Cushman WC, et al. Treatment-resistant hypertension and the incidence of cardiovascular disease and end-stage renal disease: results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension. 2014;64(5):1012-21.
- Group SR, Wright JT, Jr., Williamson JD, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015;373(22):2103-16.
- Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51(6):1403-19.
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- Stone MS, Martyn L, Weaver CM. Potassium Intake, Bioavailability, Hypertension, and Glucose Control. Nutrients. 2016;8(7).
- Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129-39.
- Sipahi I, Swaminathan A, Natesan V, et al. Effect of antihypertensive therapy on incident stroke in cohorts with prehypertensive blood pressure levels: a meta-analysis of randomized controlled trials. Stroke. 2012;43(2):432-40.
- Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol. 2009;8(5):453-63.
- Mozaffarian D, Bryson CL, Lemaitre RN, et al. Fish intake and risk of incident heart failure. J Am Coll Cardiol. 2005;45(12):2015-21.
- Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090-8.
- Benes LB, Bassi NS, Davidson MH. Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia. Vasc Health Risk Manag. 2016;12:481-90.
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- Lavie CJ, Milani RV, Mehra MR, et al. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol. 2009;54(7):585-94.
- Jacobson TA. Role of n-3 fatty acids in the treatment of hypertriglyceridemia and cardiovascular disease. Am J Clin Nutr. 2008;87(6):1981s-90s.
- Konishi H, Miyauchi K, Kasai T, et al. Impact of lipoprotein(a) as residual risk on long-term outcomes in patients after percutaneous coronary intervention. Am J Cardiol. 2015;115(2):157-60.
- Cantin B, Gagnon F, Moorjani S, et al. Is lipoprotein(a) an independent risk factor for ischemic heart disease in men? The Quebec Cardiovascular Study. J Am Coll Cardiol. 1998;31(3):519-25.
- Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23):2844-53.
- Levy DR, Pearson TA. Combination niacin and statin therapy in primary and secondary prevention of cardiovascular disease. Clin Cardiol. 2005;28(7):317-20.
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- Seidah NG. New developments in proprotein convertase subtilisin-kexin 9’s biology and clinical implications. Curr Opin Lipidol. 2016;27(3):274-81.
- Banerjee Y, Santos RD, Al-Rasadi K, et al. Targeting PCSK9 for therapeutic gains: Have we addressed all the concerns? Atherosclerosis. 2016;248:62-75.
- Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376(18):1713-22.
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