Vascular disease

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In medicine, vascular disease is "pathological processes involving any of the blood vessels in the cardiac or peripheral circulation.[1] They include diseases of arteries; veins; and rest of the vasculature system in the body." Examples of vascular diseases include coronary heart disease, cerebrovascular disorders, and peripheral vascular disease.

Prevention

Exercise

Separate to the question of the benefits of exercise; it is unclear whether doctors should spend time counseling patients to exercise. The U.S. Preventive Services Task Force (USPSTF), based on a systematic review of randomized controlled trials, found 'insufficient evidence' to recommend that doctors counsel patients on exercise.[2] However, the American Heart Association, based on a non-systematic review, recommends that doctors counsel patients on exercise [3]

Preventive diets

Dietary changes can potentially lead to large changes in the cholesterol.[4]

Aspirin

Aspirin, in doses of less than 75 to 81 mg/d[5], can reduce the incidence of cardiovascular events.[6] The U.S. Preventive Services Task Force 'strongly recommends that clinicians discuss aspirin chemoprevention with adults who are at increased risk for coronary heart disease'.[7] The Task Force defines increased risk as 'Men older than 40 years of age, postmenopausal women, and younger persons with risk factors for coronary heart disease (for example, hypertension, diabetes, or smoking) are at increased risk for heart disease and may wish to consider aspirin therapy'. More specifically, high-risk persons are 'those with a 5-year risk ≥ 3%'. A risk calculator is available.[8]

Regarding healthy women, the more recent Women's Health Study randomized controlled trial found insignficant benefit from aspirin in the reduction of cardiac events; however there was a signficant reduction in stroke.[9] Subgroup analysis showed that all benefit was confined to women over 65 years old.[9] In spite of the insignficant benefit for women < 65 years old, recent practice guidelines by the American Heart Association recommend to 'consider' aspirin in 'healthy women' <65 years of age 'when benefit for ischemic stroke prevention is likely to outweigh adverse effects of therapy'.[10]

Antilipemic drugs

The U.S. Preventive Services Task Force (USPSTF) estimated that after 5 to 7 years of treatment with statins, the relative risk reduction of coronary heart disease events is decreased by approximately 30%[11][12]. More recently, a meta-analysis reported an almost identical relative risk reduction of 29.2% in low risk patients treated for 4.3 years [13]. A relative risk reduction of 19% in coronary mortality was found in a meta-analysis of patients at all levels of risk.[14]

Various clinical practice guidelines have addressed the treatment of hypercholesterolemia. The American College of Physicians has addressed hypercholesterolemia in patients with diabetes [15]. Their recommendations are:

  • Recommendation 1: Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and morbidity for all patients (both men and women) with known coronary artery disease and type 2 diabetes.
  • Recommendation 2: Statins should be used for primary prevention against macrovascular complications in patients (both men and women) with type 2 diabetes and other cardiovascular risk factors.
  • Recommendation 3: Once lipid-lowering therapy is initiated, patients with type 2 diabetes mellitus should be taking at least moderate doses of a statin (the accompanying evidence report states "simvastatin, 40 mg/d; pravastatin, 40 mg/d; lovastatin, 40 mg/d; atorvastatin, 20 mg/d; or an equivalent dose of another statin")[16].
  • Recommendation 4: For those patients with type 2 diabetes who are taking statins, routine monitoring of liver function tests or muscle enzymes is not recommended except in specific circumstances.

The National Cholesterol Education Program revised their guidelines[17]; however, their 2004 revisions have been criticized for use of nonrandomized, observational data.[18]

Antioxidant vitamins

Initially, observational cohort cohort studies such as the Nurses' Health Study found associations between self-reported consumption of vitamin C (ascorbic acid)[19] and vitamin E (α-tocopherol).[20]


Cambridge Heart Antioxidant Study (CHAOS) -
lack of dose-response gradient
  Nonfatal MI
vitamin E 800 IU/day 2.0% (11/546)
vitamin E 400 IU/day 0.6% (3/489)
Placebo 4.2% (41/967)

The Cambridge Heart Antioxidant Study (CHAOS) was an early randomized controlled trial of vitamin E and in spite of having worse baseline characteritics in the vitamin E group, found "in patients with angiographically proven symptomatic coronary atherosclerosis, alpha-tocopherol treatment substantially reduces the rate of non-fatal MI, with beneficial effects apparent after 1 year of treatment" and no effect oncardiovascular deaths.[21] As noted in the table, the lack of a dose-response gradient makes causation less likely. The study also had less patients in the control group for uncertain reasons.

In the year 2000, the HOPE study was the first negative randomized controlled trial of Vitamin E to be published.[22] The HOPE study followed high-risk patients for a mean of 4.5 years. At the time of the HOPE study, 1 of every 8 Americans reported taking vitamin E supplements.[23]

Surprisingly, authors continued to cite positive results from earlier observations studies were refuted by the HOPE trial.[24] These authors often cited the earlier CHAOS study.[24]

In the year 2005, a meta-analysis concluded that Vitamin E supplementation may actually be harmful.[25] After this publication, sales of vitamin E fell by 33%.[26]

Subsequent trials confirmed the HOPE study. Vitamins C (500 mg) and E (400 IU) did not benefit males in the Physicians' Health Study II randomized controlled trial which started recruitment in 1997 and followed patients for a mean of 8 years.[27] Vitamin E did not benefit women in the Women's Health Study randomized controlled trial which began recruitment in 1992 and followed women for an average of 10.1 years.[28]

Omega-3 fatty acids (fish oil)

For more information, see: Fish oil.


Homocysteine lowering

A meta-analysis concluded that lowering homocysteine with folic acid and other supplements may reduce stroke.[29] However, the two largest randomized controlled trials included in the meta-analysis had conflicting results. Lonn reported positive results[30]; whereas the trial by Toole was negative.[31]

Since the meta-analysis, two additional trials have shown no reduction in cardiovascular endpoint despite successfully lowering the plasma homocysteine level.[32][33]

References

  1. Anonymous (2024), Vascular disease (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. (2002) "Behavioral counseling in primary care to promote physical activity: recommendation and rationale". Ann. Intern. Med. 137 (3): 205-7. PMID 12160370[e]
  3. Thompson PD, Buchner D, Pina IL, et al (2003). "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 107 (24): 3109-16. DOI:10.1161/01.CIR.0000075572.40158.77. PMID 12821592. Research Blogging. http://www.ngc.gov/summary/summary.aspx?ss=15&doc_id=5360&string=#s23
  4. McMurry MP, Cerqueira MT, Connor SL, Connor WE (1991). "Changes in lipid and lipoprotein levels and body weight in Tarahumara Indians after consumption of an affluent diet". N. Engl. J. Med. 325 (24): 1704-8. PMID 1944471[e]
  5. Campbell CL, Smyth S, Montalescot G, Steinhubl SR (2007). "Aspirin dose for the prevention of cardiovascular disease: a systematic review". JAMA 297 (18): 2018-24. DOI:10.1001/jama.297.18.2018. PMID 17488967. Research Blogging.
  6. Berger J, Roncaglioni M, Avanzini F, Pangrazzi I, Tognoni G, Brown D (2006). "Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials". JAMA 295 (3): 306-13. PMID 16418466.
  7. (2002) "Aspirin for the primary prevention of cardiovascular events: recommendation and rationale". Ann Intern Med 136 (2): 157-60. PMID 11790071.
  8. http://www.med-decisions.com/
  9. 9.0 9.1 Ridker P, Cook N, Lee I, Gordon D, Gaziano J, Manson J, Hennekens C, Buring J (2005). "A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women". N Engl J Med 352 (13): 1293-304. DOI:10.1056/NEJMoa050613. PMID 15753114. Research Blogging.
  10. http://circ.ahajournals.org/cgi/content/abstract/CIRCULATIONAHA.107.181546v1
  11. Pignone MP, Phillips CJ, Atkins D, Teutsch SM, Mulrow CD, Lohr KN (2001). "Screening and treating adults for lipid disorders". American journal of preventive medicine 20 (3 Suppl): 77–89. PMID 11306236[e]
  12. Screening for Lipid Disorders: Recommendations and Rationale. Retrieved on 2007-10-17.
  13. Thavendiranathan P, Bagai A, Brookhart M, Choudhry N (2006). "Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials". Arch Intern Med 166 (21): 2307-13. PMID 17130382.
  14. Baigent C, Keech A, Kearney PM, et al (2005). "Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins". Lancet 366 (9493): 1267-78. DOI:10.1016/S0140-6736(05)67394-1. PMID 16214597. Research Blogging.
  15. Snow V, Aronson M, Hornbake E, Mottur-Pilson C, Weiss K (2004). "Lipid control in the management of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians". Ann Intern Med 140 (8): 644-9. PMID 15096336.
  16. Vijan S, Hayward RA (2004). "Pharmacologic lipid-lowering therapy in type 2 diabetes mellitus: background paper for the American College of Physicians". Ann. Intern. Med. 140 (8): 650-8. PMID 15096337[e]
  17. Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB, Pasternak RC, Smith SC, Stone NJ (2004). "Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines". J. Am. Coll. Cardiol. 44 (3): 720-32. DOI:10.1016/j.jacc.2004.07.001. PMID 15358046. Research Blogging.
  18. Hayward RA, Hofer TP, Vijan S (2006). "Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem". Ann. Intern. Med. 145 (7): 520-30. PMID 17015870[e]
  19. Osganian SK, Stampfer MJ, Rimm E, et al (July 2003). "Vitamin C and risk of coronary heart disease in women". J. Am. Coll. Cardiol. 42 (2): 246–52. PMID 12875759[e]
  20. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC (May 1993). "Vitamin E consumption and the risk of coronary disease in women". N. Engl. J. Med. 328 (20): 1444–9. PMID 8479463[e]
  21. Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ (March 1996). "Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS)". Lancet 347 (9004): 781–6. DOI:10.1016/S0140-6736(96)90866-1. PMID 8622332. Research Blogging.
  22. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P (January 2000). "Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators". N. Engl. J. Med. 342 (3): 154–60. PMID 10639540[e]
  23. Muth MK, Anderson DW, Domanico JL, Smith JB, Wendling B. Economic Characterization of the Dietary Supplement Industry. Washington, DC: Center for Food Safety and Administration, Food and Drug Administration; 1999.
  24. 24.0 24.1 Tatsioni A, Bonitsis NG, Ioannidis JP (December 2007). "Persistence of contradicted claims in the literature". JAMA 298 (21): 2517–26. DOI:10.1001/jama.298.21.2517. PMID 18056905. Research Blogging.
  25. Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (January 2005). "Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality". Ann. Intern. Med. 142 (1): 37–46. PMID 15537682[e]
  26. Tilburt JC, Emanuel EJ, Miller FG (September 2008). "Does the evidence make a difference in consumer behavior? Sales of supplements before and after publication of negative research results". J Gen Intern Med 23 (9): 1495–8. DOI:10.1007/s11606-008-0704-z. PMID 18618194. PMC 2518024. Research Blogging.
  27. Sesso HD, Buring JE, Christen WG, et al (November 2008). "Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial". JAMA 300 (18): 2123–33. DOI:10.1001/jama.2008.600. PMID 18997197. Research Blogging.
  28. Lee IM, Cook NR, Gaziano JM, et al (July 2005). "Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial". JAMA 294 (1): 56–65. DOI:10.1001/jama.294.1.56. PMID 15998891. Research Blogging.
  29. Wang X, Qin X, Demirtas H, et al (2007). "Efficacy of folic acid supplementation in stroke prevention: a meta-analysis". Lancet 369 (9576): 1876-82. DOI:10.1016/S0140-6736(07)60854-X. PMID 17544768. Research Blogging. PMID 17544768
  30. Lonn E, Yusuf S, Arnold MJ, et al (2006). "Homocysteine lowering with folic acid and B vitamins in vascular disease". N. Engl. J. Med. 354 (15): 1567-77. DOI:10.1056/NEJMoa060900. PMID 16531613. Research Blogging. PMID 16531613
  31. Toole JF, Malinow MR, Chambless LE, et al (2004). "Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial". JAMA 291 (5): 565-75. DOI:10.1001/jama.291.5.565. PMID 14762035. Research Blogging. PMID 14762035
  32. ""[e]
  33. Ebbing M, Bleie O, Ueland PM, Nordrehaug JE, Nilsen DW, Vollset SE, 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.