Patients do not just wake up one morning with cardiac disease. Instead there is an extended preclinical phase during which life-style choices determine outcome. Recent advances in our understanding of oxidative stress, endocrine signaling, immune/inflammatory balance, and energy production illuminate opportunities for efficacious intervention. A thorough exploration of these pathophysiologies will allow physicians the opportunity to offer their patients a journey away from illness and disease to optimal wellness.
KremersHM, CrowsonCS, TherneauTM, RogerVL, GabrielSE. High ten-year risk of cardiovascular disease in newly diagnosed rheumatoid arthritis patients: a population-based cohort study.Arthritis Rheum.2008 Aug; 58(8): 2268–74.
2.
ShengX, MurphyMJ, MacdonaldTM, WeiL. Effectiveness of statins on total cholesterol and cardiovascular disease and all-cause mortality in osteoarthritis and rheumatoid arthritis.J Rheumatol.2012 Jan; 39(1): 32–40. Epub 2011 Nov 1.
3.
GrundySM, BrewerHBJr, CleemanJI, SmithSCJr, LenfantC. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition.Arterioscler Thromb Vasc Biol.2004 Feb; 24(2): e13–18.
4.
ParkYW, ZhuS, PalaniappanL, HeshkaS, CarnethonMR, HeymsfieldSB. The metabolic syndrome: Prevalence and associated risk factor findings in the US population from the third national health and nutrition examination survey, 1988-1984.Arch Intern Med.2003; 163: 427–436.
5.
ZhuS, WangZ, ShenW, HeymsfieldSB, HeshkaS. Percentage body fat ranges associated with metabolic syndrome risk: results based on the third national health and nutrition examination survey. 1933-1994.Am J Clin Nutr.2003; 78: 228–235.
6.
AckermannD, JonesJ, BaronaJWaist circumference is positively correlated with markers of inflammation and negatively with adiponectin in women with metabolic syndrome.Nutr Res.2011 Mar; 31(3): 197–204.
7.
WoodRJ. Vitamin D and adipogenesis: new molecular insights.Nutr Rev.2008; 66(1): 40–6.
8.
ChristakisNA, FowlerJH. The spread of obesity in a large social network over 32 years.N Engl J Med.2007; 357(4): 370–379.
9.
LudwigJ, SanbonmatsuL, GennetianLNeighborhoods, obesity, and diabetes—a randomized social experiment.N Engl J Med.2011; 365(16): 1509–19.
10.
WijeysunderaHC, MachadoM, FarahatiFAssociation of temporal trends in risk factors and treatment uptake with coronary heart disease mortality, 1994-2005.JAMA.2010; 303(18): 1841–7.
11.
FriesJ. Aging, natural death, and the compression of morbidity.N Engl J Med.1980Jul 17; 303(3): 130–5.
12.
BuettnerD. The blue zones: lessons for living longer from the people who've lived the longest.Washington, DC: National Geographic Society; 2008.
13.
CrimminsEM, Beltrán-SánchezH. Mortality and morbidity trends: is there a compression of morbidity?J Gerontol B Psychol Sci Soc Sci.2011 Jan; 66(1): 75–86. Epub 2010 Dec 6.
14.
HotamisligilGS. Inflammation and metabolic disorders.Nature.2006Dec 14; 444(7121): 860–7.
15.
ZhangX, ZhangG, ZhangH, KarinM, BaiH, CaiD. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity.Cell.2008Oct 3; 135(1): 61–73.
16.
BodenG. Endoplasmic reticulum stress: another link between obesity and insulin resistance/inflammation.Diabetes.2009 Mar; 58(3): 518–9.
17.
VirchowR. Phlogose und Thrombose im Gefässystem. In: Gesammelte Abhandlungen zur wissenschaftlichen Medizin.Frankfurt: Medinger Sohn and Co; 1856.
18.
AnitschkowNN. Über die Veränderungen der Kaninchenaorta bei experimenteller Cholesterinsteatose.Beitr Pathol Anat.1931; 56: 379–404. German.
19.
DuffGL, McMillianGC. Pathology of atherosclerosis.Am J Med.1951 Jul; 11(1): 92–108.
20.
SteinbergD. Hypercholesterolemia an inflammation in atherogenesis: two sides of the same coin.Mol Nutr Food Res.2005 Nov; 49(11): 995–8.
21.
MayerlC, LukasserM, SedivyR, NiedereggerH, SeilerR, WickG. Atherosclerosis research from past to present—on the track of two pathologists with opposing views, Carl von Rokitansky and Rudolf Virchow.Virchows Arch.2006 Jul; 449(1): 96–103.
22.
HarrisonDG, GongoraMC. Oxidative stress and hypertension.Med Clin North Am.2009 May; 93(3): 621–35.
23.
DimmelerS, FlemingI, FisslthalerB, HermannC, BusseR, ZeiherAM. Activation of NOS in endothelial cells by Akt-dependent phosphorylation.Nature.1999; 399: 601–5.
24.
BeslerC, HeinrichK, RohrerLMechanisms underlying adverse effects of HDL on eNOS-activating pathways with coronary artery disease.J Clin Invest.2011; 121(7): 2693–2708.
25.
AvignonA, SultanA. PKCßII inhibition: a new therapeutic approach for diabetic complications?Diabetes Metab.2006 Jun; 32(3): 205–13.
26.
CorrettiMC, AndersonTJ, BenjaminEJGuidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery.J Am Coll Cardiol.2002Jan 16; 39(2): 257–65.
27.
CohenJD, DruryJH, OstdiekJBenefits of lipid lowering on vascular reactivity in patients with coronary artery disease and average cholesterol levels: a mechanism for lowering clinical events?Am Heart J.2000 Apr; 139(4): 734–8.
28.
ModenaMG, BonettiL, CoppiF, BursiF, RossiR. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women.J Am Col Cardiol.2002Aug 7; 40(3): 505–10.
29.
LundbergJO, WeitzbergE, GladwinMT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics.Nat Rev Drug Discov.2008 Feb; 7(2): 156–67.
30.
BryanNS, FernandezBO, BauerSMNitrite is a signaling molecule and regulator of gene expression in mammalian tissues.Nat Chem Biol.2005 Oct; 1(5): 290–7.
StoneNJ. The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)-Prevenzione Trial on fish oil and vitamin E supplementation in myocardial infarction survivors.Curr Cardiol Rep.2000; 2(5): 445–51.
34.
MoriTA, BaoDQ, BurkeV, PuddeyIB, BeilinLJ. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans.Hypertension.1999 Aug; 34(2): 253–60.
35.
JacobsonTA, GlicksteinSB, RoweJD, SoniPN. Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review.J Clin Lipidol.2012 Jan; 6(1): 5–18. Epub 2011 Nov 3.
36.
AttakpaE, HichamiA, SimoninAM, SansónEG, DramaneKL, KhanNA. Docosahexaenoic acid modulates the expression of T-bet and GATA-3 transcription factors, independently of PPARalpha, through suppression of MAP kinase activation.Biochemie.2009; 91(11-12): 1359–65.
37.
OhDY, TalukdarS, BaeEJGPR120 is an omega-3 fatty acid receptor mediating potent-anti-inflammatory and insulin-sensitizing effects.Cell.2010Sep 3; 142(5): 687–98.
38.
GotohC, HongYH, IgaTThe regulation of adipogenesis through GPR-120.Biochem Biophys Res Com.2007Mar 9; 354(2): 591–7.
39.
IchimuraA, HirasawaA, Poulain-GodefroyODysfunction of lipid sensor GPR120 leads to obesity in both mouse and human.Nature.2012Feb 19; 483(7389): 350–4.
40.
PascoeJ, HollernD, StamaterisRFree fatty acids block glucose-induced ß-cell proliferation in mice by inducing cell cycle inhibitors p16 and p18.Diabetes.2012 Mar; 61(3): 632–41.
41.
KromhoutD, GeleijnseJM, de GoedeJn-3 fatty acids and cardiovascular events after myocardial infarction.N Engl J Med.2010Nov 18; 363(21): 2015–26.
MenkeA, MuntnerP, BatumanV, SilbergeldEK, GuallarE. Blood lead below 0.48 micromo/L (10 microg/dL) and mortality among US adults.Circulation.2006; 114(13): 1388–94.
44.
HoustonMC. The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction.Altern Ther Health Med.2007Mar-Apr;13(2): S128–33.
45.
MelikerJR, WahlRL, CameronLL, NriaguJO. Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standard mortality ratio analysis.Environ Health.2007Feb 2; 6: 4.
46.
LimJS, LeeDH, ParkJY, JinSH, JacobsDRJr. A strong interaction between serum GGT and obesity on the risk of prevalent type 2 diabetes: results from the third national health and nutrition examination survey.Clin Chem.2007 Jun; 53(6): 1092–8.
47.
RejebJ, OmezzineA, BoumaizaIElevated liver enzymes in metabolic syndrome are associated with coronary stenosis in a Tunisian population.Metab Syndr Relat Disorder.2010 Jun; 8(3): 249–54.
48.
CorkeyBE. Banting lecture 2011: hyperinsulinemia: cause or consequence?Diabetes.2012 Jan; 61(1): 4–13.
49.
ErridgeC, AttinaT, SpickettCM, WebbDJ. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation.Am J Clin Nutr.2007 Nov; 86(5): 1286–92.
50.
de KortS, KeszthelyiD, MascleeAA. Leaky gut and diabetes mellitus: what is the link?Obes Rev.2011 Jun; 12(6): 449–58. Epub 2011 Mar 8.
51.
CaniPD, DelzenneNM. Involvement of the gut micro biota in the development of low grade inflammation associated with obesity: focus on this neglected partner.Acta Gastroenterol Belg.2010Apr-Jun;73(2): 267–9.
52.
MehtaNN, McGillicuddyFC, AndersonPDExperimental endotoxemia induces adipose inflammation and insulin resistance in humans.Diabetes.2010 Jan; 59(1): 172–8.
53.
CooneyCA, DaveAA, WolffGL. Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring.J Nutr.2002Aug;132(8 Suppl):2393S–2400S.
54.
PainterRC, RoseboomTJ, BlekerOP. Prenatal exposure to the Dutch famine and disease in later life: an overview.Reprod Toxicol.2005Sep-Oct;20(3): 345–52.
55.
KnowlerWC, Barrett-ConnorE, FowlerSEReduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med.2002Feb 7; 346(6): 393–403.
56.
NieldL, SummerbellCD, HooperL, WhittakerV, MooreH. Dietary advice for treatment of type 2 diabetes mellitus in adults.Cochrane Database Syst Rev.2008 Jul 16;(3):CD005102.
57.
LuomaPV. Gene activation regresses atherosclerosis, promotes health, and enhances longevity.Lipids Health Dis.2010Jul 6; 9: 67.
58.
JacobsDRJr, SteffenLM. Nutrients, foods, and dietary patterns as exposures in research: a framework for food synergy.Am J Clin Nutr.2003Sep;78(3 Suppl):508S–13S
59.
BaronaJ, JonesJJ, KopecREA Mediterranean-style low-glycemic load diet increases plasma carotenoids and decreases LDL oxidation in women with metabolic syndrome.J Nutritional Biochem.2011 Jul 19. [Epub ahead of print]
60.
MozaffarianD, LudwigDS. Dietary guidelines in the 21st century—a time for food.JAMA.2010Aug 11; 304(6): 681–2.
61.
GoldfineAB, KaulS, HiattWR. Fibrates in the treatment of dyslipidemias—time for a reassessment.N Engl J Med.2011Aug 11; 365(6): 481–4.
62.
BaysHE, RothEM, McKenneyJMThe effects of fenofibric acid alone and with statins on the prevalence of metabolic syndrome and its diagnostic components in patients with mixed dyslipidemia.Diabetes Care.2010 Sep; 33(9): 2113–6.
63.
KasteleinJJ, AkdimF, StroesESSimvastatin with or without ezetimibe in familial hypercholesterolemia.N Engl J Med.2008Apr 3; 358(14): 1431–43.
64.
TaylorAJ, VillinesTC, StanekEJExtended-release niacin or ezetimibe and carotid intima-media thickness.N Engl J Med.2009 Nov 26;361(22):2113–22. Epub 2009 Nov 15.
65.
WarnholtzA, WildP, OstadMAEffects of oral niacin on endothelial dysfunction in patients with coronary artery disease: results of the randomized, double-blind, placebo-controlled INEF study.Atherosclerosis.2009 May; 204(1): 216–21. Epub 2008 Aug 12.
66.
OtvosJD. The surprising AIM-HIGH results are not surprising when viewed through a particle lens.J Clin Lipidol.2011 Sep; 5(5): 368–70.
67.
HamiltonSJ, ChewGT, WattsGF. Coenzyme Q10 improves endothelial dysfunction in statin-treated type 2 diabetic patients.Diabetes Care.2009 May; 32(5): 810–2. Epub 2009 Feb 19.
68.
SugdenJA, DaviesJI, WithamMD, MorrisAD, StruthersAD. Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels.Diabet Med.2008 Mar; 25(3): 320–5. Epub 2008 Feb 13.
69.
NjikeVY, FaridiZEffects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults.Int J Cardiol.2011May 19; 149(1): 83–8. Epub 2009 Dec 24.
70.
HordNG, TangY, BryanNS. Food sources of nitrates and nitrites: the physiologic context for potential health benefits.Am J Clin Nutr.2009 Jul; 90(1): 1–10. Epub 2009 May 13.
71.
TangY, GargH, GengYJ, BryanNS. Nitric oxide bioactivity of traditional Chinese medicines used for cardiovascular indications.Free Radic Biol Med.2009Sep 15; 47(6): 835–40. Epub 2009 Jun 21.
72.
BondonnoCP, YangX, CroftKDFlavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial.Free Radic Biol Med.2012Jan 1; 52(1): 95–102. Epub 2011 Oct.
73.
TrippML, KondaVR, DarlandGRho-iso-alpha acids and tetrahydro-iso-alpha acids are selective protein kinase inhibitors which potently reduce inflammation in macrophages in vitro and in the collagen-induced rheumatoid arthritis model in vivo.Acta Hort (ISHS).2009; 848: 221–234.
74.
LermanRH, MinichDM, DarlandGEnhancement of a modified Mediterranean-style, low glycemic load diet with specific phytochemicals improves cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia in a randomized trial.Nutr Metab (Lond).2008Nov 4; 5: 29.
75.
JonesJL, ComperatoreM, BaronaJA Mediterranean-style, low-glycemic-load diet decreases atherogenic lipoproteins and reduces lipoprotein (a) and oxidized low-density lipoprotein in women with metabolic syndrome.Metabolism.2012 Mar; 61(3): 366–72. Epub 2011 Sep 23.
