Life Extension Magazine May 2009
As We See It
No More Heart Attacks!
By William Faloon
By William Faloon
Sex Hormones and Inflammation in Men
Aging men are plagued with declining testosterone levels while their estrogen remains the same or even increases. This imbalance often sets the stage for a host of chronic inflammatory disorders, while increasing the amount of abdominal adiposity.
For years, we at Life Extension have advised maturing men to restore their free testosterone to youthful ranges (between 20 and 24 pg/mL of blood) and keep their estrogen from getting too high. Ideal estrogen (estradiol) levels in men have been shown to be between 20 and 30 pg/mL of blood.
We have seen countless cases of men with chronic inflammation experience a reversal of their elevated C-reactive protein (and painful symptoms) when a youthful sex hormone profile is properly restored. Independent published studies corroborate our findings that low testosterone and high estradiol predisposes aging men to chronic inflammatory status and higher C-reactive protein.30-32
Based on these findings, the overweight Crestor® study subjects could have benefited enormously if their sex hormone balance was restored to youthful ranges. It is tantalizing to think what benefits could have been shown if those who took Crestor® used these additive approaches to reduce their C-reactive protein to optimal levels.
Simple Guidelines to Protect Yourself Against Heart Attack and Stroke
At the end of this article is a reprint of our 17 “daggers aimed at the heart” diagram that represents independent risk factors associated with heart attack and stroke. Any one of these daggers can create vascular disease. Regrettably, aging people often suffer multiple risk factors (daggers aimed at their heart) that cause them to die prematurely.
Fortunately, the proper blood tests can identify risk factors unique to each individual so that corrective action can be taken before one’s heart or brain is decimated by a catastrophic vascular event.
The third article in this month’s issue discusses the 17 independent risk factors involved in vascular disease and describes the simple steps you can take to make sure that none of them causes a problem for you. As you will readily see, there is a wide range of lifestyle, nutrient, hormone, and drug choices available. If you don’t want to take drugs, plenty of natural alternatives exist. Some people will need to take drugs, however, to get into optimal ranges.
Lethal Dangers of C-Reactive Protein Elevation
Multiple studies document that a chronic inflammatory process is directly involved in the degenerative diseases of aging including cancer,89-91 dementia,92-94 stroke,95-97 visual disorders,98,99 arthritis,100-102 liver failure,103,104 and heart attack.4,105-109
Fortunately, a low-cost C-reactive protein blood test can identify whether you suffer a smoldering inflammatory fire within your body that will likely cause you to die prematurely. An abundance of scientific research provides a wide range of proven approaches to suppress chronic inflammatory reactions.33-78,110,111
The comprehensive Male and Female Blood Test Panels reveal what your C-reactive protein level is right now, along with other factors that could cause your C-reactive protein to be too high. Blood components that can spike C-reactive protein levels include high LDL,112 low HDL,113 low testosterone114 and excess estradiol (in men),115 elevated glucose,116,117 excess homocysteine,118 and DHEA deficit.119
Remember, optimal blood levels of C-reactive protein are below 0.55 mg/L in men and below 1.50 mg/L in women.12 Standard reference ranges accept higher levels as normal because so many people fail to take care of themselves and thus suffer chronically high C-reactive protein levels with subsequently increased risk of heart attack,6,120-123 stroke,6-8,124 cancer,89-91 senility,125,126 etc.127
No More Heart Attacks!
The Crestor® study showed it is possible to achieve a dramatic reduction in heart attack and stroke incidence when C-reactive protein and LDL are reduced.
Yet the same study revealed that a significant number of study subjects who suffered “major cardiovascular events” were not protected by the high dose of Crestor® they took.
This proves beyond any doubt that more than cholesterol, LDL, and C-reactive protein5,128-132 are involved in the atherosclerotic process that results in heart attack and stroke being today’s leading causes of disability and death.
If one is to achieve ultimate protection against arterial disease, all of the independent risk factors (as identified in the 17 daggers aimed at the heart graphic) have to be brought under control.
We should all be grateful to live in an era when these vascular risk factors can be easily measured and corrected before a major cardiovascular event manifests!
Lowest Blood Test Prices of the Year
Once a year, Life Extension discounts the price of the popular Male or Female Blood Test Panels. The medical establishment charges around $1,000 for these comprehensive tests, but as a Life Extension member, you can obtain the same tests for only $189 (if you order by June 1, 2009).
To review the many longevity factors included in the Male or Female Blood Test Panels, and how you can use the findings from your blood test to protect against age-related disease, refer to my article beginning on page 54 of this issue.
When you place your blood test order, we send you a requisition form along with a listing of blood-drawing stations in your area. You can normally walk in during regular business hours for a convenient blood draw.
To place your order for the comprehensive Male and/or Female Blood Test Panel, call 1-800-208-3444 or log on to www.lef.org/blood
For longer life,
1.Agmon Y, Khandheria BK, Meissner I, et al. C-reactive protein and atherosclerosis of the thoracic aorta: a population-based transesophageal echocardiographic study. Arch Intern Med. 2004 Sep 13;164(16):1781-7.
2.Patrick L, Uzick M. Cardiovascular disease: C-reactive protein and the inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol, red yeast rice, and olive oil polyphenols. A review of the literature. Altern Med Rev. 2001 Jun;6(3):248-71.
3.Dandona P. Effects of antidiabetic and antihyperlipidemic agents on C-reactive protein. Mayo Clin Proc. 2008 Mar;83(3):333-42.
4. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002 Nov 14;347(20):1557-65.
5.Montecucco F, Mach F. New evidences for C-reactive protein (CRP) deposits in the arterial intima as a cardiovascular risk factor. Clin Interv Aging. 2008;3(2):341-9.
6.Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997 Apr 3;336(14):973-9.
7.Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998 Aug 25;98(8):731-3.
8.Ballantyne CM, Hoogeveen RC, Bang H, et al. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Arch Intern Med. 2005 Nov 28;165(21):2479-84.
9.Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207.
10. Anty R, Bekri S, Luciani N, et al. The inflammatory C-reactive protein is increased in both liver and adipose tissue in severely obese patients independently from metabolic syndrome, Type 2 diabetes, and NASH. Am J Gastroenterol. 2006 Aug;101(8):1824-33.
11.Available at: http://www.medscape.com/viewarticle/513056. Accessed February 19, 2009.
12.Available at: http://www.lef.org/protocols/appendix/blood_testing_02.htm. Accessed February 19, 2009.
13.Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999 Dec 8;282(22):2131-5.
14.Block G, Jensen CD, Dalvi TB, et al. Vitamin C treatment reduces elevated C-reactive protein. Free Radic Biol Med. 2009 Jan 1;46(1):70-7.
15.Available at: http://berkeley.edu/news/media/releases/2008/11/12_vitaminc.shtml. Accessed February 19, 2009.
16.Baillargeon J, Rose DP. Obesity, adipokines, and prostate cancer (review). Int J Oncol. 2006 Mar;28(3):737-45.
17.Abu-Abid S, Szold A, Klausner J. Obesity and cancer. J Med. 2002;33(1-4):73-86.
18.Morimoto LM, White E, Chen Z, et al. Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative (United States). Cancer Causes Control. 2002 Oct;13(8):741-51.
19.Bonora E. The metabolic syndrome and cardiovascular disease. Ann Med. 2006;38(1):64-80.
20.Ridker PM. Inflammatory biomarkers and risks of myocardial infarction, stroke, diabetes, and total mortality: implications for longevity. Nutr Rev. 2007 Dec;65(12 Pt 2):S253-9.
21.Haffner SM. Abdominal adiposity and cardiometabolic risk: do we have all the answers? Am J Med. 2007 Sep;120(9 Suppl 1):S10-6.
22.Semiz S, Rota S, Ozdemir O, Ozdemir A, Kaptanoglu B. Are C-reactive protein and homocysteine cardiovascular risk factors in obese children and adolescents? Pediatr Int. 2008 Aug;50(4):419-23.
23.Haffner SM. Relationship of metabolic risk factors and development of cardiovascular disease and diabetes. Obesity (Silver Spring). 2006 Jun;14(Suppl 3):121S-S.
24.Whitmer RA. The epidemiology of adiposity and dementia. Curr Alzheimer Res. 2007 Apr;4(2):117-22.
25.Petersson H, Lind L, Hulthe J, Elmgren A, Cederholm T, Riserus U. Relationships between serum fatty acid composition and multiple markers of inflammation and endothelial function in an elderly population. Atherosclerosis. 2008 Jul 1.
26.Levitan EB, Cook NR, Stampfer MJ, et al. Dietary glycemic index, dietary glycemic load, blood lipids, and C-reactive protein. Metabolism. 2008 Mar;57(3):437-43.
27.Pirro M, Schillaci G, Savarese G, et al. Attenuation of inflammation with short-term dietary intervention is associated with a reduction of arterial stiffness in subjects with hypercholesterolaemia. Eur J Cardiovasc Prev Rehabil. 2004 Dec;11(6):497-502.
28.Jenkins DJ, Kendall CW, Marchie A, et al. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA. 2003 Jul 23;290(4):502-10.
29.Ajani UA, Ford ES, Mokdad AH. Dietary fiber and C-reactive protein: findings from national health and nutrition examination survey data. J Nutr. 2004 May;134(5):1181-5.
30.Tang YJ, Lee WJ, Chen YT, et al. Serum testosterone level and related metabolic factors in men over 70 years old. J Endocrinol Invest. 2007 Jun;30(6):451-8.
31.Nakhai Pour HR, Grobbee DE, Muller M, Van der Schouw YT. Association of endogenous sex hormone with C-reactive protein levels in middle-aged and elderly men. Clin Endocrinol (Oxf). 2007 Mar;66(3):394-8.
32.Choi BG, McLaughlin MA. Why men’s hearts break: cardiovascular effects of sex steroids. Endocrinol Metab Clin North Am. 2007 Jun;36(2):365-77.
33.Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of turmeric (Curcuma longa). J Altern Complement Med. 2003 Feb;9(1):161-8.
34.Zhang F, Altorki NK, Mestre JR, Subbaramaiah K, Dannenberg AJ. Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis. 1999 Mar;20(3):445-51.
35.Satoskar RR, Shah SJ, Shenoy SG. Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int J Clin Pharmacol Ther Toxicol. 1986 Dec;24(12):651-4.
36.Ramsewak RS, DeWitt DL, Nair MG. Cytotoxicity, antioxidant and anti-inflammatory activities of curcumins I-III from Curcuma longa. Phytomedicine. 2000 Jul;7(4):303-8.
37.Pendurthi UR, Williams JT, Rao LV. Inhibition of tissue factor gene activation in cultured endothelial cells by curcumin. Suppression of activation of transcription factors Egr-1, AP-1, and NF-kappa B. Arterioscler Thromb Vasc Biol. 1997 Dec;17(12):3406-13.
38.Oben JE, Ngondi JL, Blum K. Inhibition of Irvingia gabonensis seed extract (OB131) on adipogenesis as mediated via down regulation of the PPARgamma and Leptin genes and up-regulation of the adiponectin gene. Lipids Health Dis. 2008;744.
39.Available at: http://stanford.wellsphere.com/healthy-eating-article/more-information-on-irvingia/544189. Accessed Feb 12, 2009.
40.Ngondi JL, Oben JE, Minka SR. The effect of Irvingia gabonensis seeds on body weight and blood lipids of obese subjects in Cameroon. Lipids Health Dis. 2005 May 25;412.
41.Shea MK, Booth SL, Massaro JM, et al. Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study. Am J Epidemiol. 2008 Feb 1;167(3):313-20.
42.Reddi K, Henderson B, Meghji S, et al. Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is potently inhibited by naphthoquinone (vitamin K) compounds. Cytokine. 1995 Apr;7(3):287-90.
43.Ozaki I, Zhang H, Mizuta T, et al. Menatetrenone, a vitamin K2 analogue, inhibits hepatocellular carcinoma cell growth by suppressing cyclin D1 expression through inhibition of nuclear factor kappaB activation. Clin Cancer Res. 2007 Apr 1;13(7):2236-45.
44.Ueda H, Yamazaki C, Yamazaki M. Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. Biol Pharm Bull. 2002 Sep;25(9):1197-202.
45.Das M, Ram A, Ghosh B. Luteolin alleviates bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice. Inflamm Res. 2003 Mar;52(3):101-6.
46.Xagorari A, Papapetropoulos A, Mauromatis A, et al. Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J Pharmacol Exp Ther. 2001 Jan;296(1):181-7.
47.Wu D, Han SN, Meydani M, Meydani SN. Effect of concomitant consumption of fish oil and vitamin E on production of inflammatory cytokines in healthy elderly humans. Ann NY Acad Sci. 2004 Dec;1031:422-4.
48.Lo CJ, Chiu KC, Fu M, Lo R, Helton S. Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF kappa B activity. J Surg Res. 1999 Apr;82(2):216-21.
49.Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ. The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr. 1996 Jan;63(1):116-22.
50.Kremer JM. n-3 fatty acid supplements in rheumatoid arthritis. Am J Clin Nutr. 2000 Jan;71(1 Suppl):349S-51S.
51. Jolly CA, Muthukumar A, Avula CP, Troyer D, Fernandes G. Life span is prolonged in food-restricted autoimmune-prone (NZB x NZW)F(1) mice fed a diet enriched with (n-3) fatty acids. J Nutr. 2001 Oct;131(10):2753-60.
52.Pischon T, Hankinson SE, Hotamisligil GS, et al. Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation. 2003 Jul 15;108(2):155-60.
53.Madsen T, Skou HA, Hansen VE, et al. C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease. Am J Cardiol. 2001 Nov 15;88(10):1139-42.
54.Kast RE. Borage oil reduction of rheumatoid arthritis activity may be mediated by increased cAMP that suppresses tumor necrosis factor-alpha. Int Immunopharmacol. 2001 Nov;1(12):2197-9.
55.Rothman D, DeLuca P, Zurier RB. Botanical lipids: effects on inflammation, immune responses, and rheumatoid arthritis. Semin Arthritis Rheum. 1995 Oct;25(2):87-96.
55.Izgut-Uysal VN, Agac A, Derin N. Effect of L-carnitine on carrageenan-induced inflammation in aged rats. Gerontology. 2003 Sep;49(5):287-92.
56.Bellinghieri G, Santoro D, Calvani M, Savica V. Role of carnitine in modulating acute-phase protein synthesis in hemodialysis patients. J Ren Nutr. 2005 Jan;15(1):13-7.
57.Savica V, Calvani M, Benatti P, et al. Carnitine system in uremic patients: molecular and clinical aspects. Semin Nephrol. 2004 Sep;24(5):464-8.
58.Maramag C, Menon M, Balaji KC, Reddy PG, Laxmanan S. Effect of vitamin C on prostate cancer cells in vitro: effect on cell number, viability, and DNA synthesis. Prostate. 1997 Aug 1;32(3):188-95.
59.Calabrese V, Giuffrida Stella AM, Calvani M, Butterfield DA. Acetylcarnitine and cellular stress response: roles in nutritional redox homeostasis and regulation of longevity genes. J Nutr Biochem. 2006 Feb;17(2):73-88.
60.Wei DZ, Yang JY, Liu JW, Tong WY. Inhibition of liver cancer cell proliferation and migration by a combination of (-)-epigallocatechin-3-gallate and ascorbic acid. J Chemother. 2003 Dec;15(6):591-5.
61.Sanchez-Moreno C, Cano MP, de AB, et al. High-pressurized orange juice consumption affects plasma vitamin C, antioxidative status and inflammatory markers in healthy humans. J Nutr. 2003 Jul;133(7):2204-9.
63.Kaul D, Baba MI. Genomic effect of vitamin ‘C’ and statins within human mononuclear cells involved in atherogenic process. Eur J Clin Nutr. 2005 Aug;59(8):978-81.
64.Korantzopoulos P, Kolettis TM, Kountouris E, et al. Oral vitamin C administration reduces early recurrence rates after electrical cardioversion of persistent atrial fibrillation and attenuates associated inflammation. Int J Cardiol. 2005 Jul 10;102(2):321-6.
65.Majewicz J, Rimbach G, Proteggente AR, et al. Dietary vitamin C down-regulates inflammatory gene expression in apoE4 smokers. Biochem Biophys Res Commun. 2005 Dec 16;338(2):951-5.
66.Aneja R, Odoms K, Denenberg AG, Wong HR. Theaflavin, a black tea extract, is a novel anti-inflammatory compound. Crit Care Med. 2004 Oct;32(10):2097-103.
67.Pan MH, Lin-Shiau SY, Ho CT, Lin JH, Lin JK. Suppression of lipopolysaccharide-induced nuclear factor-kappaB activity by theaflavin-3,3’-digallate from black tea and other polyphenols through down-regulation of IkappaB kinase activity in macrophages. Biochem Pharmacol. 2000 Feb 15;59(4):357-67.
68.Liang YC, Tsai DC, Lin-Shiau SY, et al. Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory skin edema and ornithine decarboxylase activity by theaflavin-3,3’-digallate in mouse. Nutr Cancer. 2002;42(2):217-23.
69.Lin JK. Cancer chemoprevention by tea polyphenols through modulating signal transduction pathways. Arch Pharm Res. 2002 Oct;25(5):561-71.
70.Cai F, Li CR, Wu JL, et al. Theaflavin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-inflammatory effect and modulation of STAT-1. Mediators Inflamm. 2006;2006(5):30490.
71.Siddiqui IA, Adhami VM, Afaq F, Ahmad N, Mukhtar H. Modulation of phosphatidylinositol-3-kinase/protein kinase B- and mitogen-activated protein kinase-pathways by tea polyphenols in human prostate cancer cells. J Cell Biochem. 2004 Feb 1;91(2):232-42.
72.Ma Y, Hebert JR, Li W, et al. Association between dietary fiber and markers of systemic inflammation in the Women’s Health Initiative Observational Study. Nutrition. 2008 Oct;24(10):941-9.
73.Jacobs LR. Relationship between dietary fiber and cancer: metabolic, physiologic, and cellular mechanisms. Proc Soc Exp Biol Med. 1986 Dec;183(3):299-310.
74.Galvez J, Rodriguez-Cabezas ME, Zarzuelo A. Effects of dietary fiber on inflammatory bowel disease. Mol Nutr Food Res. 2005 Jun;49(6):601-8.
75.Qi L, van Dam RM, Liu S, et al. Whole-grain, bran, and cereal fiber intakes and markers of systemic inflammation in diabetic women. Diabetes Care. 2006 Feb;29(2):207-11.
76. Wang XL, Rainwater DL, Mahaney MC, Stocker R. Cosupplementation with vitamin E and coenzyme Q10 reduces circulating markers of inflammation in baboons. Am J Clin Nutr. 2004 Sep;80(3):649-55.
77. Kunitomo M, Yamaguchi Y, Kagota S, Otsubo K. Beneficial effect of coenzyme Q10 on increased oxidative and nitrative stress and inflammation and individual metabolic components developing in a rat model of metabolic syndrome. J Pharmacol Sci. 2008 Jun;107(2):128-37.
78. Chan YH, Lau KK, Yiu KH, et al. Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke. Eur Heart J. 2008 Nov;29(22):2800-7.
79. Joyal S. Guard your precious proteins against premature aging. Life Extension. 2008 Apr;14(3):37-43.
80. Vlassara H, Cai W, Crandall J, et al. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci USA. 2002 Nov 26;99(24):15596-601.
81. Dyer DG, Blackledge JA, Katz BM, et al. The Maillard reaction in vivo. Z Ernahrungswiss. 1991 Feb;30(1):29-45.
82. Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med. 2000 Jun 15;28(12):1708-16.
83. Mustapha IZ, Debrey S, Oladubu M, Ugarte R. Markers of systemic bacterial exposure in periodontal disease and cardiovascular disease risk: a systematic review and meta-analysis. J Periodontol. 2007 Dec;78(12):2289-302.
84. Moutsopoulos NM, Madianos PN. Low-grade inflammation in chronic infectious diseases: paradigm of periodontal infections. Ann NY Acad Sci. 2006 Nov;1088:251-64.
85. Loos BG, Craandijk J, Hoek FJ, Wertheim-van Dillen PM, Van Der Velden U., Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients. J Periodontol. 2000 Oct;71(10):1528-34.
86. Wu T, Trevisan M, Genco RJ, et al. Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. Am J Epidemiol. 2000 Feb 1;151(3):273-82.
87. Abou-Raya S, Bou-Raya A, Naim A, Abuelkheir H. Rheumatoid arthritis, periodontal disease and coronary artery disease. Clin Rheumatol. 2008 Apr;27(4):421-7.
88. Paquette DW. The periodontal-cardiovascular link. Compend Contin Educ Dent. 2004 Sep;25(9):681-92.
89. Chiu HM, Lin JT, Chen TH, et al. Elevation of C-reactive protein level is associated with synchronous and advanced colorectal neoplasm in men. Am J Gastroenterol. 2008 Sep;103(9):2317-25.
90. Groblewska M, Mroczko B, Wereszczynska-Siemiatkowska U, et al. Serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels in colorectal adenoma and cancer patients. Clin Chem Lab Med. 2008;46(10):1423-8.
91. Caruso C, Lio D, Cavallone L, Franceschi C. Aging, longevity, inflammation, and cancer. Ann NY Acad Sci. 2004 Dec;1028:1-13.
92. Paganelli R, Di IA, Patricelli L, et al. Proinflammatory cytokines in sera of elderly patients with dementia: levels in vascular injury are higher than those of mild-moderate Alzheimer’s disease patients. Exp Gerontol. 2002 Jan;37(2-3):257-63.
93. Zuliani G, Ranzini M, Guerra G, et al. Plasma cytokines profile in older subjects with late onset Alzheimer’s disease or vascular dementia. J Psychiatr Res. 2007 Oct;41(8):686-93.
94. Yaffe K, Kanaya A, Lindquist K, et al. The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004 Nov 10;292(18):2237-42.
95. Di Napoli M, Papa F, Bocola V. C-reactive protein in ischemic stroke: an independent prognostic factor. Stroke. 2001 Apr;32(4):917-24.
96. Shantikumar S, Grant PJ, Catto AJ, Bamford JM, Carter AM. Elevated C-Reactive Protein and Long-Term Mortality After Ischaemic Stroke. Relationship With Markers of Endothelial Cell and Platelet Activation. Stroke. 2009 Jan 22.
97. Sabatine MS, Morrow DA, Jablonski KA, et al. Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation. 2007 Mar 27;115(12):1528-36.
98. Boekhoorn SS, Vingerling JR, Witteman JC, Hofman A, de Jong PT. C-reactive protein level and risk of aging macula disorder: The Rotterdam Study. Arch Ophthalmol. 2007 Oct;125(10):1396-401.
99. Seddon JM, Gensler G, Milton RC, Klein ML, Rifai N. Association between C-reactive protein and age-related macular degeneration. JAMA. 2004 Feb 11;291(6):704-10.
100. Joosten LA, Netea MG, Kim SH, et al. IL-32, a proinflammatory cytokine in rheumatoid arthritis. Proc Natl Acad Sci USA. 2006 Feb 28;103(9):3298-303.
101. Mosaad YM, Metwally SS, Auf FA, et al. Proinflammatory cytokines (IL-12 and IL-18) in immune rheumatic diseases: relation with disease activity and autoantibodies production. Egypt J Immunol. 2003;10(2):19-26.
102. Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, et al. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci USA. 2003 Jul 22;100(15):9090-5.
103. Antoniades CG, Berry PA, Wendon JA, Vergani D. The importance of immune dysfunction in determining outcome in acute liver failure. J Hepatol. 2008 Nov;49(5):845-61.
104. Mani AR, Montagnese S, Jackson CD, et al. Decreased heart rate variability in patients with cirrhosis relates to the presence and degree of hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G330-8.
105. Jialal I, Devaraj S. Inflammation and atherosclerosis: the value of the high-sensitivity C-reactive protein assay as a risk marker. Am J Clin Pathol. 2001 Dec;116(Suppl):S108-15.
106. Kuch B, von Scheidt W, Kling B, et al. Differential impact of admission C-reactive protein levels on 28-day mortality risk in patients with ST-elevation versus non-ST-elevation myocardial infarction (from the Monitoring Trends and Determinants on Cardiovascular Diseases [MONICA]/Cooperative Health Research in the Region of Augsburg [KORA] Augsburg Myocardial Infarction Registry). Am J Cardiol. 2008 Nov 1;102(9):1125-30.
107. Jeppesen J, Hansen TW, Olsen MH, et al. C-reactive protein, insulin resistance and risk of cardiovascular disease: a population-based study. Eur J Cardiovasc Prev Rehabil. 2008 Oct;15(5):594-8.
108. Mach F. Inflammation is a crucial feature of atherosclerosis and a potential target to reduce cardiovascular events. Handb Exp Pharmacol. 2005;(170):697-722.
109. Kanda T. C-reactive protein (CRP) in the cardiovascular system. Rinsho Byori. 2001 Apr;49(4):395-401.
110. McMillan DC, Leen E, Smith J, et al. Effect of extended ibuprofen administration on the acute phase protein response in colorectal cancer patients. Eur J Surg Oncol. 1995 Oct;21(5):531-4.
111. Ikonomidis I, Andreotti F, Economou E, et al. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation. 1999 Aug 24;100(8):793-8.
112. Arena R, Arrowood JA, Fei DY, Helm S, Kraft KA. The relationship between C-reactive protein and other cardiovascular risk factors in men and women. J Cardiopulm Rehabil. 2006 Sep-Oct;26(5):323-7; quiz 328-9.
113. Sampietro T, Bigazzi F, Dal PB, et al. Increased plasma C-reactive protein in familial hypoalphalipoproteinemia: a proinflammatory condition? Circulation. 2002 Jan 1;105(1):11-4.
114. Malkin CJ, Pugh PJ, Jones RD, Jones TH, Channer KS. Testosterone as a protective factor against atherosclerosis--immunomodulation and influence upon plaque development and stability. J Endocrinol. 2003 Sep;178(3):373-80.
115. Nakhai Pour HR, Grobbee DE, Muller M, van der Schouw YT. Association of endogenous sex hormone with C-reactive protein levels in middle-aged and elderly men. Clin Endocrinol (Oxf). 2007 Mar;66(3):394-8.
116. Shankar A, Li J. Positive association between high-sensitivity C-reactive protein level and diabetes mellitus among US non-Hispanic black adults. Exp Clin Endocrinol Diabetes. 2008 Aug;116(8):455-60.
117. Aronson D, Avizohar O, Levy Y, Bartha P, Jacob G, Markiewicz W. Factor analysis of risk variables associated with low-grade inflammation. Atherosclerosis. 2008 Sep;200(1):206-12.
118. Holven KB, Aukrust P, Retterstol K, et al. Increased levels of C-reactive protein and interleukin-6 in hyperhomocysteinemic subjects. Scand J Clin Lab Invest. 2006;66(1):45-54.
119. Tengstrand B, Carlstrom K, Fellander-Tsai L, Hafstrom I. Abnormal levels of serum dehydroepiandrosterone, estrone, and estradiol in men with rheumatoid arthritis: high correlation between serum estradiol and current degree of inflammation. J Rheumatol. 2003 Nov;30(11):2338-43.
120. Rifai N, Ridker PM. Inflammatory markers and coronary heart disease. Curr Opin Lipidol. 2002 Aug;13(4):383-9.
121. Albert CM, Ma J, Rifai N, Stampfer MJ, Ridker PM. Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation. 2002 Jun 4;105(22):2595-9.
122. Bermudez EA, Ridker PM. C-reactive protein, statins, and the primary prevention of atherosclerotic cardiovascular disease. Prev Cardiol. 2002;5(1):42-6.
123. Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation. 2004 Jun 1;109(21 Suppl 1):II2-10.
124. Di Napoli M, Papa F, Bocola V. Prognostic influence of increased C-reactive protein and fibrinogen levels in ischemic stroke. Stroke. 2001 Jan;32(1):133-8.
125. Nilsson K, Gustafson L, Hultberg B. C-reactive protein: vascular risk marker in elderly patients with mental illness. Dement Geriatr Cogn Disord. 2008;26(3):251-6.
126. Komulainen P, Lakka TA, Kivipelto M, et al. Serum high sensitivity C-reactive protein and cognitive function in elderly women. Age Ageing. 2007 Jul;36(4):443-8.
127. Maugeri D, Russo MS, Franze C, et al. Correlations between C-reactive protein, interleukin-6, tumor necrosis factor-alpha and body mass index during senile osteoporosis. Arch Gerontol Geriatr. 1998 Sep;27(2):159-63.
128. Teoh H, Quan A, Lovren F, et al. Impaired endothelial function in C-reactive protein overexpressing mice. Atherosclerosis. 2008 Dec;201(2):318-25.
129. Singh U, Devaraj S, Vasquez-Vivar J, Jialal I. C-reactive protein decreases endothelial nitric oxide synthase activity via uncoupling. J Mol Cell Cardiol. 2007 Dec;43(6):780-91.
130. Bisoendial RJ, Kastelein JJ, Stroes ES. C-reactive protein and atherogenesis: from fatty streak to clinical event. Atherosclerosis. 2007 Dec;195(2):e10-8.
131. Schwedler SB, Kuhlencordt PJ, Ponnuswamy PP, et al. Native C-reactive protein induces endothelial dysfunction in ApoE-/- mice: implications for iNOS and reactive oxygen species. Atherosclerosis. 2007 Dec;195(2):e76-84.
132. Ferri C, Croce G, Cofini V, et al. C-reactive protein: interaction with the vascular endothelium and possible role in human atherosclerosis. Curr Pharm Des. 2007;13(16):1631-45.
133. Ebbing M, Bleie O, Ueland PM, et al. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA. 2008 Aug 20;300(7):795-804.
134. Jarosz A, Nowicka G. C-reactive protein and homocysteine as risk factors of atherosclerosis. Przegl Lek. 2008;65(6):268-72.