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Management of Dyslipidemia in Patients with Hypertension, Diabetes, and Metabolic Syndrome

  • Hypertension and Obesity (E Reisin, Section Editor)
  • Published:
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Abstract

Purpose of Review

The purpose of this review is to discuss dyslipidemia in the various common clinical conditions including hypertension, diabetes mellitus, and metabolic syndrome and review the current therapeutic strategy in these settings.

Recent Findings

Dyslipidemias are common in patients with hypertension, diabetes mellitus, and metabolic syndrome. Epidemiologic studies have shown a strong correlation between serum lipid levels and risk of atherosclerotic cardiovascular disease. Multifactorial intervention strategies aimed at controlling lipids, blood pressure, and blood glucose simultaneously achieve maximal reductions in cardiovascular risk.

Summary

Dyslipidemia and metabolic abnormalities are strongly associated with atherosclerosis and worse cardiovascular outcomes. While pharmacotherapy with statins has been proven to be beneficial for dyslipidemia, lifestyle modification emphasizing weight loss and regular exercise is an essential component of the interventional strategy. The common thread underlying atherosclerosis and metabolic abnormalities is endothelial dysfunction. Improved understanding of the role of endothelium in health and disease can potentially lead to novel therapies that may preempt development of atherosclerosis and its complications.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Twickler T, Dallinga-Thie GM, Chapman MJ, Cohn JS. Remnant lipoproteins and atherosclerosis. Curr Atheroscler Rep. 2005;7:140–7.

    Article  CAS  PubMed  Google Scholar 

  2. Varbo A, Benn M, Tybaerg-Hansen A, Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol. 2013;61:427–36.

    Article  CAS  PubMed  Google Scholar 

  3. Grundy SM. Small LDL, atheogenic dyslipidemia and the metabolic syndrome. Circulation. 1997;95:1–4. Defines atherogenic dyslipidemia and highlights the role of dyslipidemia in relation to cardiovascular events.

    Article  CAS  PubMed  Google Scholar 

  4. Frostegard J. Immunity, atherosclerosis and cardiovascular disease. BMC Med. 2013;11:117.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wang J, Razuvaev A, Folkersen L, et al. The expression of IGFs and IGF binding proteins in human carotid atherosclerosis, and the possible role of IGF binding protein-1 in the regulation of smooth muscle cell proliferation. Atherosclerosis. 2012;220:102–9.

    Article  CAS  PubMed  Google Scholar 

  6. Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R. Update on acute coronary syndromes: the pathologists’ view. Eur Heart J. 2013;34:719–28.

    Article  CAS  PubMed  Google Scholar 

  7. Cannon CP, Braunwald E, McCabe CH, et al. Pravastatin or atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22 investigators. Intensive versus moderate lipid-lowering with statins after acute coronary syndrome. N Engl J Med. 2004;350(15):1495–504.

    Article  CAS  PubMed  Google Scholar 

  8. Van Wijk DF, Sjouke B, Figueroa A, et al. Nonpharmacological lipoprotein apheresis reduces arterial inflammation in familial hypercholesterolemia. J Am Coll Cardiol. 2014;64:1418–26.

    Article  PubMed  Google Scholar 

  9. Cohen JC, Boerwinkle E, Mosley Jr TH, Hoobs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354:1264–72. One of the original studies correlating lower LDL levels with mutations in PCSK9, with significant reductions in cardiovascular risk.

    Article  CAS  PubMed  Google Scholar 

  10. The Myocardial Infarction Genetics Consortium Investigators. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med. 2014;371:2072–82.

    Article  PubMed Central  Google Scholar 

  11. Lloyd-Jones DM, Liu K, Colangelo LA, et al. Consistently stable or decreased body mass index in young adulthood and longitudinal changes in metabolic syndrome components: the Coronary Artery Risk Development in Young Adults Study. Circulation. 2007;115:1004–11.

    Article  PubMed  Google Scholar 

  12. Yanovski SZ, Yanovski JA. Obesity. N Engl J Med. 2002;346:591–602.

    Article  CAS  PubMed  Google Scholar 

  13. Haslam DW, James WPT. Obesity. Lancet. 2005;366:1197–209.

    Article  PubMed  Google Scholar 

  14. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans—2010. Accessed at http://www.cnpp.usda.gov/dietary-guidelines-2010 on 26 Jan. 2016.

  15. Scientific Report of the 2015 Dietary Guidelines Advisory Committee. Accessed at http://www.health.gov/dietaryguidelines/2015-scientific-report/ on 26 January 2016.

  16. Esposito K, Marfella R, Ciotola M, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA. 2004;292:1440–6.

    Article  CAS  PubMed  Google Scholar 

  17. Tortosa A, Bes-Rastrollo M, Sanchez-Villegas A, et al. Mediterranean diet inversely associated with the incidence of metabolic syndrome: the SUN prospective cohort. Diabetes Care. 2007;30:2957–9.

    Article  PubMed  Google Scholar 

  18. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403.

    Article  CAS  PubMed  Google Scholar 

  19. Thompson PD, Buchner D, Pina IL, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation. 2003;107:3109–16.

    Article  PubMed  Google Scholar 

  20. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, 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;376:1670–81.

    Article  Google Scholar 

  21. Cholesterol Treatment Trialists’ Collaboration, Mihaylova B, Emberson J, Blackwell L, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–90.

    Article  Google Scholar 

  22. Grundy SM, Cleeman JI, Merz CN, Brewer Jr HB, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program ATP III guidelines. Circulation. 2004;110(2):227–39.

    Article  PubMed  Google Scholar 

  23. 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.

    Google Scholar 

  24. Expert Dyslipidemia Panel of the International Atherosclerosis Society Panel members. An International Atherosclerosis Society Position Paper: global recommendations for the management of dyslipidemia—full report. J Clin Lipidol. 2014;8:29–60. The International Atherosclerosis Society has developed a new set of recommendations for the management of dyslipidemia.

    Article  Google Scholar 

  25. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S1–45. Current evidence based guidelines for management of hyperlipidemia from ACC/AHA.

    Article  Google Scholar 

  26. American Diabetes Association. Standards of medical care in diabetes—2016. Diabetes Care. 2016;39 suppl 1:S1–106. Document outlining current recommended management goals for diabetes mellitus.

    Google Scholar 

  27. Keene D, Price C, Shun-Shin MJ, Francis DP. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomized controlled trials including 117,411 patients. BMJ. 2014;349:g4379.

  28. AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–67. Correction in N Engl J Med. 2012;367:189.

    Article  Google Scholar 

  29. HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–12. Definitive study which shows ineffectiveness of niacin therapy on improving cardiovascular outcomes along with significant increases in the rates of serious adverse events with addition of niacin therapy.

    Article  Google Scholar 

  30. Pischon T, Girman CJ, Sacks FM, Rifai N, Stampfer MJ, Rimm EB. Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation. 2005;112:3375–83.

    Article  CAS  PubMed  Google Scholar 

  31. Kastelein JJ, van der Steeg WA, Holme I, TNT Study Group, IDEAL Study Group, et al. Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation. 2008;117:3002–9.

    Article  CAS  PubMed  Google Scholar 

  32. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489–99. Phase 3 study of newly released biologic PCSK9 inhibitor alirocumab.

    Article  CAS  PubMed  Google Scholar 

  33. Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: UKPDS 23. BMJ. 1998;316:823–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Heart Protection Study Collaborative Group. MCR/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5,963 people with diabetes: a randomized placebo-controlled trial. Lancet. 2003;361:2005–16.

    Article  Google Scholar 

  35. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomized placebo-controlled trial. Lancet. 2004;364:685–96.

    Article  CAS  PubMed  Google Scholar 

  36. Sposito AC, Mansur AP, Coelho OR, et al. Additional reduction in blood pressure after cholesterol-lowering treatment by statins (lovastatin or pravastatin) in hypercholesterolemic patients using angiotensin-converting enzyme inhibitors (enalapril or lisinopril). Am J Cardiol. 1999;83:1497–9.

    Article  CAS  PubMed  Google Scholar 

  37. Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. ALLHAT. JAMA. 2002;288(23):2981–97.

    Article  Google Scholar 

  38. Dahlof B, Sever PS, Poulter NR, for the ASCOT Investigators, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicenter randomized controlled trial. Lancet. 2005;366:895–906.

    Article  PubMed  Google Scholar 

  39. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular event in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:145–53.

    Article  CAS  PubMed  Google Scholar 

  40. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet. 2002;359(9311):995–1003.

    Article  CAS  PubMed  Google Scholar 

  41. NAVIGATOR Study Group. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362(16):1463–76.

    Article  Google Scholar 

  42. De Cavanagh EM, Piotrkowski B, Basso N, Stella I, Inserra F, Ferder L, et al. Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. FASEB J. 2003;17:1096–8.

    PubMed  Google Scholar 

  43. De Cavanagh EM, Inserra F, Toblli J, Stella I, Fraga CG, Ferder L. Enalapril attenuates oxidative stress in diabetic rats. Hypertension. 2001;38:1130–6.

    Article  PubMed  Google Scholar 

  44. Furuhashi M, Ura N, Higashiura K, et al. Blockade of the rennin-angiotensin system increases adiponectin concentrations in patients with essential hypetenstion. Hypertension. 2003;42:76–81.

    Article  CAS  PubMed  Google Scholar 

  45. Engeli S. Role of the renin-angiotensin-aldosterone system in the metabolic syndrome. Contrib Nephrol. 2006;151:122–34.

    Article  PubMed  Google Scholar 

  46. Krejs GJ. Metabolic benefits associated with sibutramine therapy. Int J Obesit. 2002;26 Suppl 4:S34–7.

    Article  CAS  Google Scholar 

  47. James WP, Caterson ID, Coutinho W, SCOUT Investigators, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010;363:905–17.

    Article  CAS  PubMed  Google Scholar 

  48. Mark EJ, Patalas ED, Chang HT, et al. Fatal pulmonary hypertension associated with short-term use of fenfluramine and phentermine. N Engl J Med. 1997;337:602–6. Published correction appears in: N Engl J Med 1997;337:1483.

    Article  CAS  PubMed  Google Scholar 

  49. Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluraminephentermine. N Engl J Med. 1997;337:581–8. Published correction appears in: N Engl J Med 1997;337:1783.

    Article  CAS  PubMed  Google Scholar 

  50. Didangelos TP, Thanapoulou AK, Bousboulas SH, et al. The orlistat and cardiovascular risk profile in patients with the metabolic syndrome and type 2 diabetes (ORLICARDIA) study. Curr Med Res Opin. 2004;20:1393–401.

    Article  CAS  PubMed  Google Scholar 

  51. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. Xenical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study or orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27:155–61.

    Article  CAS  PubMed  Google Scholar 

  52. Xie S, Furjanic MA, Ferrara JJ, McAndrew NR, Ardino EL, Ngondara A, et al. The endocannabinoid system and rimonabant: a new drug with a novel mechanism of action involving cannabinoid CB1 receptor antagonism—or inverse agonism—as potential obesity treatment and other therapeutic use. J Clin Pharm Ther. 2007;32(3):209–31.

    Article  CAS  PubMed  Google Scholar 

  53. Patel PN, Pathak R. Rimonabant: a novel selective cannabinoid—1 receptor antagonist for treatment of obesity. Am J Health Syst Pharm. 2007;64(5):481–9.

    Article  CAS  PubMed  Google Scholar 

  54. Sweeting AN, Tabet E, Caterson ID, et al. Management of obesity and cardiometabolic risk—role of phentermine/extended release topiramate. Diab Metab Synd Obes. 2014;7:35–44.

    CAS  Google Scholar 

  55. Astrup A, Carraro R, Finer N, NN8022- 1807 Investigators, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012;36:843–54.

    Article  CAS  Google Scholar 

  56. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring). 2011;19:110–20.

    Article  CAS  Google Scholar 

  57. Shukla AP, Buniak WI, Aronne LJ. Treatment of obesity in 2015. J Cardiopulm Rehab Prev. 2015;35:81–92.

    Article  Google Scholar 

  58. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. FDA Briefing Document NDA 200063 Contrave (Naltrexone 4 mg, 8 mg/Bupropion HCL 90 mg extended release tablet). 2010 Advisory Committee—December 7, 2010. Rockville, MD: U.S. Food and Drug Administration; 2010.

  59. Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/ bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013;21:935–43.

    Article  CAS  Google Scholar 

  60. Hollander P, Gupta AK, Plodkowski R, COR-Diabetes Study Group, et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013;36:4022–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Greenway FL, Fujioka K, Plodkowski RA, COR-I Study Group, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, doubleblind, placebo-controlled, phase 3 trial. Lancet. 2010;376:595–605.

    Article  CAS  PubMed  Google Scholar 

  62. Vilsbøll T, Christensen M, Junker AE, et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and metaanalyses of randomised controlled trials. BMJ. 2012;344:d7771.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Marso SP, Poulter NR, Nissen SE, LEADER Trial Investigators, et al. Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome Results (LEADER) trial. Am Heart J. 2013;166:823–30. Liraglutide in the management of diabetes mellitus and weight loss.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. UCSF School of Medicine, Fresno, CA, USA

    Sundararajan Srikanth

  2. Division of Cardiovascular Diseases, UCSF Program at Fresno CA, Fresno, CA, USA

    Sundararajan Srikanth

  3. UCSF School of Medicine, San Francisco Suite 460, 2335 E Kashian Lane, Fresno, CA, 93701, USA

    Prakash Deedwania

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Correspondence to Prakash Deedwania.

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Drs. Srikanth and Deedwania declare no conflicts of interest relevant to this manuscript.

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This article is part of the Topical Collection on Hypertension and Obesity

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Srikanth, S., Deedwania, P. Management of Dyslipidemia in Patients with Hypertension, Diabetes, and Metabolic Syndrome. Curr Hypertens Rep 18, 76 (2016). https://doi.org/10.1007/s11906-016-0683-0

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