New Concepts in Cardiovascular Disease
Mark C Houston


Cardiovascular disease
Immune vascular dysfunction
Oxidative stress


We have reached a limit in our ability to reduce the incidence of coronary heart disease and cardiovascular disease utilizing the traditional evaluation, prevention, and treatment strategies for the top five cardiovascular risk factors—hypertension, diabetes mellitus, dyslipidemia, obesity and smoking. Statistics show that approximately 50% of patients continue to have coronary heart disease or myocardial infarction despite traditionally defined “normal” levels of these five risk factors. A more logical and in-depth understanding is required of these top five risk factors, including, the evaluation of 24-hour ambulatory blood pressure monitoring, advanced lipid profiles, dysglycemic parameters, visceral obesity, with the effects of adipokines and of the three finite vascular endothelial responses (which include inflammation, oxidative stress and immune vascular dysfunction) to the infinite number of insults. Understanding translational cardiovascular medicine to correlate the coronary heart disease risk factors to the presence or absence of vascular injury and disease with non-invasive vascular testing will allow for early identification, prevention and treatment of coronary heart disease and cardiovascular disease.



Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. INTERHEART Study Investigators. Lancet. 2004; 364(9438):937–52.
World Health Organization. Cardiovascular diseases (CVDs). Fact Sheet No. 317. Accessed August 07, 2013. 2013. Available at: .
Houston MC. What Your Doctor May Not Tell You About Heart Disease. The Revolutionary Book that Reveals the Truth Behind Coronary Illnesses and How You Can Fight Them. Grand Central Life and Style. New York: Hachette Book Group, 2012.
O’Donnell CJ, Nabel EG. Genomics of cardiovascular disease. N Engl J Med. 2011; 365(22):2098–109.
Houston MC. Nutrition and nutraceutical supplements in the treatment of hypertension. Expert Rev Cardiovasc Ther. 2010; 8:821–33.
ACCORD Study Group, Gerstein HC, Miller ME, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011; 364(9):818–28.
Harper CR, Jacobson TA. Treating isolated low high-density lipoprotein cholesterol: prescient or premature? Am J Cardiol. 2000; 85(4):484–6.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). J Am Med Assoc. 2001; 285(19):2486–97.
Youssef-Elabd EM, McGee KC, Tripathi G, et al. Acute and chronic saturated fatty acid treatment as a key instigator of the TLR-mediated inflammatory response in human adipose tissue, in vitro. J Nutr Biochem. 2012; 23:39–50.
El Khatib N, Génieys S, Kazmierczak B, Volpert V. Mathematical modelling of atherosclerosis as an inflammatory disease. Philos Transact A Math Phys Eng Sci. 2009; 367(1908):4877–86.
Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Arch Intern Med. 1997; 157:2413–46.
National Cholesterol Education Program (NCEP) Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002; 106:3143–421.
American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005; 28(Suppl 1):S4–S36.
Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: pathophysiology and clinical trial evidence (risk factors through stable coronary artery disease). Circulation. 2006; 114(25):2850–70.
Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part II: clinical trial evidence (acute coronary syndromes through renal disease) and future directions. Circulation. 2006; 114(25):2871–91.
Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ. Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol. 2004; 44(3):720–32.
Port S, Garfinkel A, Boyle N. There is a non-linear relationship between mortality and blood pressure. Eur Heart J. 2000; 21(20):1635–38.
Brunner EJ, Shipley MJ, Witte DR, Fuller JH, Marmot MG. Relation between blood glucose and coronary mortality over 33 years in the Whitehall Study. Diabetes Care. 2006; 29(1):26–31.
Kannel WB, McGee D, Gordon T. A general cardiovascular risk profile: the Framingham Study. Am J Cardiol. 1976; 38(1):46–51.
Houston MC, Bestermann WH, Ferrario CM, et al. Addressing the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome in the southeastern United States: Part I. Am J Med Sci. 2005; 329:276–91.
Houston MC. Handbook of Hypertension. Oxford: Wiley-Blackwell, 2009.
Della Rocca DG, Pepine CJ. Endothelium as a predictor of adverse outcomes. Clin Cardiol. 2010; 33(12):730–2.
Houston M. The role of nutraceutical supplements in the treatment of dyslipidemia. J Clin Hypertens (Greenwich). 2012; 14(2):121–32.
Osterud B, Bjorklid E. Role of monocytes in atherogenesis. Physiol Rev. 2003; 83(4):1069–112.
Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol. 2005; 25(1):29–38.
Esper RJ, Nordaby RA, Vilariño JO, Paragano A, Cacharrón JL, Machado RA. Endothelial dysfunction: a comprehensive appraisal. Cardiovasc Diabetol. 2006; 5:4.
Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006; 83(2):456S–60S.
Brown NJ. Aldosterone and vascular inflammation. Hypertension. 2008; 51(2):161–7.
Pauletto P, Rattazzi M. Inflammation and hypertension: the search for a link. Nephrol Dial Transplant. 2006; 21(4):850–3.
Tian N, Penman AD, Mawson AR, Manning RD Jr, Flessner MF. Association between circulating specific leukocyte types and blood pressure: the atherosclerosis risk in communities (ARIC) study. J Am Soc Hypertens. 2010; 4(6):272–83.
Muller DN, Kvakan H, Luft FC. Immune-related effects in hypertension and target-organ damage. Curr Opin Nephrol Hypertens. 2011; 20(2):113–7.
Herrada AA, Campino C, Amador CA, Michea LF, Fardella CE, Kalergis AM. Aldosterone as a modulator of immunity: implications in the organ damage. J Hypertens. 2011; 29(9):1684–92.
Harrison DG, Vinh A, Lob H, Madhur MS. Role of the adaptive immune system in hypertension. Curr Opin Pharmacol. 2010; 10(2):203–7.
Marvar PJ, Thabet SR, Guzik TJ, Lob HE, McCann LA, Weyand C, Gordon FJ, Harrison DG. Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension. Circ Res. 2010; 107(2):263–70.
Schiffrin EL. T lymphocytes: a role in hypertension? Curr Opin Nephrol Hypertens. 2010; 19(2):181–6.
Lundberg AM, Yan ZQ. Innate immune recognition receptors and damage-associated molecular patterns in plaque inflammation. Curr Opin Lipidol. 2011; 22(5):343–9.
Speer T, Rohrer L, Blyszczu P, Shroff R, et al. Abnormal high-density lipoprotein induces endothelial dysfuntion via activation of Tol-like receptor-2. Immunity. 2013; 38(4):754–68.
Falck-Hansen M, Kassiteridi C, Monaco C. Toll-Like Receptors in Atherosclerosis. Int. J. Mol. Sci. 2013; 14:14008–23.
Opitz B, Eitel J, Meixenberger K, Suttorp N. Role of Toll-like receptors, NOD-like receptors and RIG-I-like receptors in endothelial cells and systemic infections. Thromb Haemost. 2009; 102:1103–9.
Zhao L, Lee JY, Hwang DH. Inhibition of pattern recognition receptor-mediated inflammation by bioactive phytochemicals. Nutr Rev. 2011; 69(6):310–20.
Layne J, Majkova Z, Smart EJ, Toborek M, Hennig B. Caveolae: a regulatory platform for nutritional modulation of inflammatory diseases. J Nutr Biochem. 2011; 22(9):807–11.
Ansar S, Koska J, Reaven PD. Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk: focus on incretins. Cardiovasc Diabetol. 2011; 10:61.
Mah E, Bruno RS. Postprandial hyperglycemia on vascular endothelial function: Mechanisms and consequences. Nutr Res. 2012; 32(10):727–40.
Folsom AR, Parker ED, Harnack LJ. Degree of concordance with DASH diet guidelines and incidence of hypertension and fatal cardiovascular disease. Am J Hypertens. 2007; 20(3):225–32.
Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med. 2000; 343(1):16–22.
Fan J, Song Y, Wang Y, Hui R, Zhang W. Dietary glycemic index, glycemic load, and risk of coronary heart disease, stroke, and stroke mortality: a systematic review with meta-analysis. PLoS One. 2012; 7(12):e52182.
Solomon TP, Haus JM, Kelly KR, Cook MD, Riccardi M, Rocco M, Kashyap SR, Barkoukis H, Kirwan JP. Randomized trial on the effects of a 7-d low-glycemic diet and exercise intervention on insulin resistance in older obese humans. Am J Clin Nutr. 2009; 90(5):1222–9.
Qi L, Hu FB. Dietary glycemic load, whole grains, and systemic inflammation in diabetes: the epidemiological evidence. Curr Opin Lipidol. 2007; 18(1):3–8.
Kario K, Shimada K, Pickering TG. Abnormal nocturnal blood pressure falls in elderly hypertension: clinical significance and determinants. J Cardiovasc Pharmacol. 2003; 41(Suppl1):S61–S66.
Hermida RC, Ayala DE, Mojón A, Fernández JR. Blunted sleep-time relative blood pressure decline increases cardi-ovascular risk independent of blood pressure level—the “normotensive non-dipper” paradox. Chronobiol Int. 2013; 30(1–2):87–98.
International Society for Chronobiology; American Association of Medical Chronobiology and Chronotherapeutics; Spanish Society of Applied Chronobiology, Chronotherapy, and Vascular Risk; Spanish Society of Atherosclerosis; Ro-manian Society of Internal Medicine, Hermida RC, Smolensky MH, Ayala DE, Portaluppi F. 2013 ambulatory blood pressure monitoring recommendations for the diagnosis of adult hypertension, assessment of cardiovascular and other hypertension-associated risk, and attainment of therapeutic goals. Chronobiol Int. 2013; 30(3):355–410.
Franco V, Oparil S, Carretero OA. Hypertensive therapy: Part I. Circulation. 2004; 109(24):2953–8.
Franklin SS, Larson MG, Khan SA, Wong ND, Leip EP, Kannel WB, Levy D. Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study. Circulation. 2001; 103:1245–9.
O’Brien E, Waeber B, Parati G, Staessen J, Myers MG. Blood pressure measuring devices: recommendations of the European Society of Hypertension. Br Med J. 2001; 322:531–6.
Redon J. The importance of 24-hour ambulatory blood pressure monitoring in patients at risk of cardiovascular events. High Blood Press Cardiovasc Prev. 2013; 20(1):13–18.
Fazio S, Linton MF. High-density lipoprotein therapeutics and cardiovascular prevention. J Clin Lipidol. 2010; 4(5):411–9.
van der Steeg WA, Holme I, Boekholdt SM, et al. High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: Significance for cardiovascular risk: The IDEAL and EPIC-Norfolk studies. J Am Coll Cardiol. 2008; 51(6):634–42.
Cromwell WC, Barringer TA. Low-density lipoprotein and apolipoprotein B: clinical use in patients with coronary heart disease. Curr Cardiol Rep. 2009; 11(6):468–75.
Mackey RH, Greenland P, Goff DC Jr, Lloyd-Jones D, Sibley CT, Mora S. High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (multi-ethnic study of atherosclerosis). J Am Coll Cardiol. 2012; 60(6):508–16.
Houston M. What Your Doctor May Not Tell You About Hypertension. The Revolutionary Nutrition and Lifestyle Program to Help Fight High Blood Pressure. New York: Hachette Book Group, 2003.
Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Kuvin JT, Lerman AJ. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. Am Coll Cardiol. 2004; 44(11):2137–41.
Rozanski A, Gransar H, Shaw LJ, et al. Impact of coronary artery calcium scanning on coronary risk factors and downstream testing the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) prospective randomized trial. J Am Coll Cardiol. 2011; 57(15):1622–32.
Kandori A, Ogata K, Miyashita T, et al. Subtraction magnetocardiogram for detecting coronary heart disease. Ann Noninvasive Electrocardiol. 2010; 15(4):360–8.
Moerland M, Kales AJ, Schrier L, van Dongen MG, Bradnock D, Burggraaf J. Evaluation of the EndoPAT as a tool to assess endothelial function. Int J Vasc Med . 2012; 2012:904141.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY-NC-ND 4.0). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.