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'''Coronary heart disease''' is caused by abnormalities the arteries that suppy the heart with blood. Those arteries are called the [[coronary artery|coronary arteries]] and the usual cause of coronary artery disease is [[athersosclerosis]]. Atherosclerosis is a degenerative disease of the arterial walls, in which the normal elastic walls of the arteries become thickened and replaced with deposits of fatty material, including [[cholesterol]]. As the walls of the affected arteries thicken, the hollow lumen at the center of each, that conduit through which oxygen enriched blood normally pulses, becomes narrower and, eventually, the flow of blood within it is decreased. With narrowing of the artery's lumen and reduced flow comes the risk of sudden occlusion of the artery, especially if the lining is abnormally roughened by deposits of irregular plaques of minerals and fats.  
'''Coronary heart disease''' is caused by abnormalities the arteries that suppy the heart with blood. Those arteries are called the [[coronary artery|coronary arteries]] and the usual cause of coronary artery disease is [[athersosclerosis]]. Atherosclerosis is a degenerative disease of the arterial walls, in which the normal elastic walls of the arteries become thickened and replaced with deposits of fatty material, including [[cholesterol]]. As the walls of the affected arteries thicken, the hollow lumen at the center of each, that conduit through which oxygen enriched blood normally pulses, becomes narrower and, eventually, the flow of blood within it is decreased. With narrowing of the artery's lumen and reduced flow comes the risk of sudden occlusion of the artery, especially if the lining is abnormally roughened by deposits of irregular plaques of minerals and fats.  


==Prevention==
==Prevention==
Line 19: Line 18:


Regarding healthy women, the more recent [[Women's Health Study]] [[randomized controlled trial]] found [[statistical significance|insignficant]] benefit from aspirin in the reduction of cardiac events; however there was a [[statistical significance|signficant]] reduction in [[stroke]].<ref name="pmid15753114">{{cite journal |author=Ridker P, Cook N, Lee I, Gordon D, Gaziano J, Manson J, Hennekens C, Buring J |title=A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women |journal=N Engl J Med |volume=352 |issue=13 |pages=1293-304 |year=2005 |pmid=15753114 | rul=http://content.nejm.org/cgi/content/full/352/13/1293 | doi=10.1056/NEJMoa050613}}</ref> [[Subgroup analysis]] showed that all benefit was confined to women over 65 years old.<ref name="pmid15753114" /> In spite of the [[statistical significance|insignficant]] benefit for women < 65 years old, recent [[Clinical practice guideline|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'.<ref>http://circ.ahajournals.org/cgi/content/abstract/CIRCULATIONAHA.107.181546v1</ref>
Regarding healthy women, the more recent [[Women's Health Study]] [[randomized controlled trial]] found [[statistical significance|insignficant]] benefit from aspirin in the reduction of cardiac events; however there was a [[statistical significance|signficant]] reduction in [[stroke]].<ref name="pmid15753114">{{cite journal |author=Ridker P, Cook N, Lee I, Gordon D, Gaziano J, Manson J, Hennekens C, Buring J |title=A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women |journal=N Engl J Med |volume=352 |issue=13 |pages=1293-304 |year=2005 |pmid=15753114 | rul=http://content.nejm.org/cgi/content/full/352/13/1293 | doi=10.1056/NEJMoa050613}}</ref> [[Subgroup analysis]] showed that all benefit was confined to women over 65 years old.<ref name="pmid15753114" /> In spite of the [[statistical significance|insignficant]] benefit for women < 65 years old, recent [[Clinical practice guideline|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'.<ref>http://circ.ahajournals.org/cgi/content/abstract/CIRCULATIONAHA.107.181546v1</ref>
===Antilipemic drugs===
The [http://www.ahrq.gov/clinic/uspstfix.htm 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% <ref name="pmid11306236">.</ref> <ref name="webPignone">.</ref>. More recently, a [[meta-analysis]] reported an almost identical  [[relative risk reduction]] of 29.2% in low risk patients treated for 4.3 years <ref name="pmid17130382">{{cite journal |author=Thavendiranathan P, Bagai A, Brookhart M, Choudhry N |title=Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials |journal=Arch Intern Med |volume=166 |issue=21 |pages=2307-13 |year=2006 |pmid=17130382}}</ref>. A [[relative risk reduction]] of 19% in coronary mortality was found in a [[meta-analysis]] of patients at all levels of risk.<ref name="pmid16214597">{{cite journal |author=Baigent C, Keech A, Kearney PM, ''et al'' |title=Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins |journal=Lancet |volume=366 |issue=9493 |pages=1267-78 |year=2005 |pmid=16214597 |doi=10.1016/S0140-6736(05)67394-1}}</ref>
Various [[clinical practice guidelines]] have addressed the treatment of hypercholesterolemia. The [[American College of Physicians]] has addressed hypercholesterolemia in patients with [[diabetes]] <ref name="pmid15096336">{{cite journal |author=Snow V, Aronson M, Hornbake E, Mottur-Pilson C, Weiss K |title=Lipid control in the management of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians |journal=Ann Intern Med |volume=140 |issue=8 |pages=644-9 |year=2004 |pmid=15096336 | url=http://www.annals.org/cgi/content/full/140/8/644}}</ref>. 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")<ref name="pmid15096337">{{cite journal |author=Vijan S, Hayward RA |title=Pharmacologic lipid-lowering therapy in type 2 diabetes mellitus: background paper for the American College of Physicians |journal=Ann. Intern. Med. |volume=140 |issue=8 |pages=650-8 |year=2004 |pmid=15096337 |doi=|url=http://www.annals.org/cgi/content/full/140/8/650}}</ref>.
* 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<ref name="pmid15358046">{{cite journal |author=Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB, Pasternak RC, Smith SC, Stone NJ |title=Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines |journal=J. Am. Coll. Cardiol. |volume=44 |issue=3 |pages=720-32 |year=2004 |pmid=15358046 |doi=10.1016/j.jacc.2004.07.001}}</ref>; however, their 2004 revisions have been criticized for use of nonrandomized, observational data.<ref name="pmid17015870">{{cite journal |author=Hayward RA, Hofer TP, Vijan S |title=Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem |journal=Ann. Intern. Med. |volume=145 |issue=7 |pages=520-30 |year=2006 |pmid=17015870 |doi=}}</ref>


===Omega-3 fatty acids (fish oil)===
===Omega-3 fatty acids (fish oil)===
The benefit of fish oil is controversial with conflicting conclusions reached by a negative [[meta-analysis]]<ref name="pmid16565093">{{cite journal |author=Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins JP, Capps NE, Riemersma RA, Ebrahim SB, Davey Smith G |title=Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review |journal=BMJ |volume=332 |issue=7544 |pages=752-60 |year=2006 |pmid=16565093 |doi=10.1136/bmj.38755.366331.2F}}</ref> of [[randomized controlled trials]] by the international [[Cochrane Collaboration]] and a partially positive [[systematic review]]<ref name="pmid16825676">{{cite journal |author=Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J |title=n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review |journal=Am. J. Clin. Nutr. |volume=84 |issue=1 |pages=5-17 |year=2006 |pmid=16825676 |doi=}} http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1a.chapter.38290</ref> by the [[Agency for Healthcare Research and Quality]]. Since these two reviews, a [[randomized controlled trial]] reported a reduction on coronary events in Japanese hypercholesterolemic patients.<ref name="pmid17398308">{{cite journal |author=Yokoyama M, Origasa H, Matsuzaki M, ''et al'' |title=Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis |journal=Lancet |volume=369 |issue=9567 |pages=1090-8 |year=2007 |pmid=17398308 |doi=10.1016/S0140-6736(07)60527-3}}</ref>
The benefit of fish oil is controversial with conflicting conclusions reached by a negative [[meta-analysis]]<ref name="pmid16565093">{{cite journal |author=Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins JP, Capps NE, Riemersma RA, Ebrahim SB, Davey Smith G |title=Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review |journal=BMJ |volume=332 |issue=7544 |pages=752-60 |year=2006 |pmid=16565093 |doi=10.1136/bmj.38755.366331.2F}}</ref> of [[randomized controlled trials]] by the international [[Cochrane Collaboration]] and a partially positive [[systematic review]]<ref name="pmid16825676">{{cite journal |author=Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J |title=n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review |journal=Am. J. Clin. Nutr. |volume=84 |issue=1 |pages=5-17 |year=2006 |pmid=16825676 |doi=}} http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1a.chapter.38290</ref> by the [[Agency for Healthcare Research and Quality]]. Since these two reviews, a [[randomized controlled trial]] reported a reduction on coronary events in Japanese hypercholesterolemic patients.<ref name="pmid17398308">{{cite journal |author=Yokoyama M, Origasa H, Matsuzaki M, ''et al'' |title=Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis |journal=Lancet |volume=369 |issue=9567 |pages=1090-8 |year=2007 |pmid=17398308 |doi=10.1016/S0140-6736(07)60527-3}}</ref>


==Lowering homocysteine==
===Homocysteine lowering===
A [[meta-analysis]] concluded that lowering [[homocysteine]] with folic acid and other supplements may reduce stroke.<ref name="pmid17544768">{{cite journal |author=Wang X, Qin X, Demirtas H, ''et al'' |title=Efficacy of folic acid supplementation in stroke prevention: a meta-analysis |journal=Lancet |volume=369 |issue=9576 |pages=1876-82 |year=2007 |pmid=17544768 |doi=10.1016/S0140-6736(07)60854-X}}PMID 17544768</ref> However, the two largest [[randomized controlled trails]] included in the meta-analysis had conflicting results. Lonn reported positve results<ref name="pmid16531613">{{cite journal |author=Lonn E, Yusuf S, Arnold MJ, ''et al'' |title=Homocysteine lowering with folic acid and B vitamins in vascular disease |journal=N. Engl. J. Med. |volume=354 |issue=15 |pages=1567-77 |year=2006 |pmid=16531613 |doi=10.1056/NEJMoa060900}}PMID 16531613</ref>; whereas the trial by Toole was negative.<ref name="pmid14762035">{{cite journal |author=Toole JF, Malinow MR, Chambless LE, ''et al'' |title=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 |journal=JAMA |volume=291 |issue=5 |pages=565-75 |year=2004 |pmid=14762035 |doi=10.1001/jama.291.5.565}}PMID 14762035</ref>
A [[meta-analysis]] concluded that lowering [[homocysteine]] with folic acid and other supplements may reduce stroke.<ref name="pmid17544768">{{cite journal |author=Wang X, Qin X, Demirtas H, ''et al'' |title=Efficacy of folic acid supplementation in stroke prevention: a meta-analysis |journal=Lancet |volume=369 |issue=9576 |pages=1876-82 |year=2007 |pmid=17544768 |doi=10.1016/S0140-6736(07)60854-X}}PMID 17544768</ref> However, the two largest [[randomized controlled trails]] included in the meta-analysis had conflicting results. Lonn reported positve results<ref name="pmid16531613">{{cite journal |author=Lonn E, Yusuf S, Arnold MJ, ''et al'' |title=Homocysteine lowering with folic acid and B vitamins in vascular disease |journal=N. Engl. J. Med. |volume=354 |issue=15 |pages=1567-77 |year=2006 |pmid=16531613 |doi=10.1056/NEJMoa060900}}PMID 16531613</ref>; whereas the trial by Toole was negative.<ref name="pmid14762035">{{cite journal |author=Toole JF, Malinow MR, Chambless LE, ''et al'' |title=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 |journal=JAMA |volume=291 |issue=5 |pages=565-75 |year=2004 |pmid=14762035 |doi=10.1001/jama.291.5.565}}PMID 14762035</ref>


==References==
==References==
<references/>
<references/>

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Coronary heart disease is caused by abnormalities the arteries that suppy the heart with blood. Those arteries are called the coronary arteries and the usual cause of coronary artery disease is athersosclerosis. Atherosclerosis is a degenerative disease of the arterial walls, in which the normal elastic walls of the arteries become thickened and replaced with deposits of fatty material, including cholesterol. As the walls of the affected arteries thicken, the hollow lumen at the center of each, that conduit through which oxygen enriched blood normally pulses, becomes narrower and, eventually, the flow of blood within it is decreased. With narrowing of the artery's lumen and reduced flow comes the risk of sudden occlusion of the artery, especially if the lining is abnormally roughened by deposits of irregular plaques of minerals and fats.

Prevention

Coronary heart disease is the most common form of heart disease in the Western world. Prevention centers on the modifiable risk factors, which include decreasing cholesterol levels, addressing obesity and hypertension, avoiding a sedentary lifestyle, making healthy dietary choices, and stopping smoking. There is some evidence that lowering uric acid and homocysteine levels may contribute. In diabetes mellitus, there is little evidence that blood sugar control actually improves cardiac risk. Some recommend a diet rich in omega-3 fatty acids and vitamin C. The World Health Organization (WHO) recommends "low to moderate alcohol intake" to reduce risk of coronary heart disease.[1]

An increasingly growing number of other physiological markers and homeostatic mechanisms are currently under scientific investigation. Among these markers are low density lipoprotein and asymmetric dimethylarginine. Patients with CHD and those trying to prevent CHD are advised to avoid fats that are readily oxidized (e.g., saturated fats and trans-fats), limit carbohydrates and processed sugars to reduce production of Low density lipoproteins while increasing High density lipoproteins, keeping blood pressure normal, exercise and stop smoking. These measures limit the progression of the disease. Recent studies have shown that dramatic reduction in LDL levels can cause mild regression of coronary heart disease.

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]

Omega-3 fatty acids (fish oil)

The benefit of fish oil is controversial with conflicting conclusions reached by a negative meta-analysis[19] of randomized controlled trials by the international Cochrane Collaboration and a partially positive systematic review[20] by the Agency for Healthcare Research and Quality. Since these two reviews, a randomized controlled trial reported a reduction on coronary events in Japanese hypercholesterolemic patients.[21]

Homocysteine lowering

A meta-analysis concluded that lowering homocysteine with folic acid and other supplements may reduce stroke.[22] However, the two largest randomized controlled trails included in the meta-analysis had conflicting results. Lonn reported positve results[23]; whereas the trial by Toole was negative.[24]

References

  1. ↑ http://www.who.int/nutrition/topics/5_population_nutrient/en/index12.html
  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. ↑ .
  12. ↑ .
  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. ↑ Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins JP, Capps NE, Riemersma RA, Ebrahim SB, Davey Smith G (2006). "Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review". BMJ 332 (7544): 752-60. DOI:10.1136/bmj.38755.366331.2F. PMID 16565093. Research Blogging.
  20. ↑ Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J (2006). "n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review". Am. J. Clin. Nutr. 84 (1): 5-17. PMID 16825676. [e] http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1a.chapter.38290
  21. ↑ Yokoyama M, Origasa H, Matsuzaki M, et al (2007). "Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis". Lancet 369 (9567): 1090-8. DOI:10.1016/S0140-6736(07)60527-3. PMID 17398308. Research Blogging.
  22. ↑ 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
  23. ↑ 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
  24. ↑ 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
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