Vascular disease

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This editable Main Article is under development and subject to a disclaimer.

[edit intro]

## Contents

* 1 Prevention
* 1.1 Exercise
* 1.2 Preventive diets
* 1.3 Alcohol
* 1.4 Aspirin
* 1.4.1 Clinical practice guidelines
* 1.4.2 Systematic reviews
* 1.4.3 Other studies
* 1.5 Anticholesteremic agents
* 1.6 Antioxidant vitamins
* 1.7 Omega-3 fatty acids (fish oil)
* 1.8 Homocysteine lowering
* 1.9 Vitamin D
* 1.10 Angiotensin-converting enzyme inhibitors
* 1.11 Evidence table
* 2 Prognosis
* 2.1 Framingham risk
* 2.2 Ankle brachial index (ABI)
* 2.3 Reynolds Score
* 2.4 C-reactive protein (CRP)
* 3 References

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

## Prevention[edit]

### Exercise[edit]

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[edit]

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

### Alcohol[edit]

The World Health Organization (WHO) recommends "low to moderate alcohol intake" to reduce risk of coronary heart disease.[5]

### Aspirin[edit]

#### Clinical practice guidelines[edit]

The U.S. Preventive Services Task Force has addressed this topic.[6][7]

USPSTF: Risk level at which benefit of aspirin exceeds harm.[6][7] Men | Women

|

Age | 10 year CHD risk | Age | 10 year stroke risk
45-59 years | ≥ 4% | 50-59 years | ≥ 3%
60-69 years | ≥ 9% | 60-69 years | ≥ 8%
70-79 years | ≥ 12% | 70-79 years | ≥ 11%
calculator | Stroke calculator

* If on NSAID: multiple rates by 4
* If prior PUD: multiply rates by 2 to 3

The European Society of Cardiology has addressed this topic and concluded, "."[8]

#### Systematic reviews[edit]

The Antithrombotic Trialists' (ATT) Collaboration has conducted a collaborative meta-analysis of individual participant data and concluded that aspirin reduced serious vascular events with a rate ratio [RR] 0·88 (95% CI 0·82–0·94]).[9] However, the benefit was not found in patients with projected 5 year risk greater than 10%.

Aspirin, in doses of less than 75 to 81 mg/d[10], can reduce the incidence of cardiovascular events.[11] In most cases the net benefit is less than 1 patient among 100.[7] A more recent meta-analysis suggests the benefit is not clear, especially for patients on statins.[9] An accompanying editorial[12], offers a cost-benefit analysis that recommends aspirin if the 10 year risk of vascular disease is at least 30%.[12]

The benefit for diabetics is not clear.[13]

#### Other studies[edit]

In a trial of patients with ankle brachial index of less than 0.9, aspirin did not help although 11% of patients had events at 8 years.[14]

Aspirin should be considered even if bleeding peptic ulcer disease has occurred.[15]

### Anticholesteremic agents[edit]

For more information, see: Hypercholesterolemia.

### Antioxidant vitamins[edit]

For more information, see: Antioxidant.

Antioxidant vitamins are not beneficial.

### Omega-3 fatty acids (fish oil)[edit]

For more information, see: Fish oil.

Omega-3 fatty acids may have small benefit[16][17], but results of randomized controlled trials are not consistent. The benefit may be at conferred on 2% of patients who take omega-3 fatty acids.[16]

### Homocysteine lowering[edit]

Lowering of homocystein blood concentration with folic acid, vitamin B12, and vitamin B6 is not beneficial.

A meta-analysis concluded that lowering homocysteine with folic acid and other supplements may reduce stroke.[18] However, the two largest randomized controlled trials included in the meta-analysis had conflicting results. Lonn reported positive results[19]; whereas the trial by Toole was negative.[20]

Since the meta-analysis, two additional randomized controlled trials have shown no reduction in cardiovascular endpoint despite successfully lowering the plasma homocysteine level.[21][22]

### Vitamin D[edit]

Vitamin D may help prevent vascular disease.[23]

### Angiotensin-converting enzyme inhibitors[edit]

The Heart Outcomes Prevention Evaluation (HOPE) study suggested that the angiotensin-converting enzyme inhibitor ramipril could reduce vascular disease and mortality among patients at increased risk. This effect was thought to be independent of control of blood pressure.[24][25][26] However, subsequent studies have shown this result was more likely due to the administration of ramipril at night and recording blood pressures during the day when the least effect of ramipril was present.[27][28]

### Evidence table[edit]

Interventions to prevent all-cause mortality
among patients at risk of vascular disease  | Study type | Relative risk ratio or odds ratio
for all-cause mortality

|
|

Aspirin[11] | Systematic review of 6 RCTs through 2005
(Does not include negative JPAD trial[29]) | Men OR=0.93
Women OR=0.94
Statin[30] | Systematic review of 7 RCTs through 2005
(Does not include positive Jupiter[31] or negative GISSI-HF[32] trials) | RR=0.92
Fish oil[33] | Systematic review of 12 RCTs through 2006
(Does not include positive GISSI-HF[17]) | OR=0.92
No systematic review reported a significant decrease in mortality.

## Prognosis[edit]

Many new biomarkers have been studied for their ability to improvement upon prediction based on traditional risk factors.[34]

Prediction of vascular disease  | Outcome | Result

|
|

Framingham plus ankle brachial index | 10-year total mortality, cardiovascular mortality, and major coronary event | Total reclassification: 19% (men); 36% (women)[35]
Traditional risk factors (Framingham) plus coronary calcium score | coronary heart disease events | Net reclassification improvement 25%[36]
Traditional risk factors (Framingham) plus c-reactive protein | "myocardial infarction and CHD-related death" | Net reclassification improvement = 12%[37]
Traditional risk factors plus c-reactive protein and family history of MI before age 60 (Reynolds Score) | All cardiovascular events | Net reclassification improvement = 8% (in men)[38]

Regarding coronary heart disease, about 3/4 of its prognosis is due to three risk factors: hypercholesterolemia (total cholesterol > 182 mg/dL [4.71 mmol/L]), hypertension (diastolic blood pressure > 90 mm Hg), and cigarette smoking.[39]

### Framingham risk[edit]

The Framingham risk uses clinical risk factors that are combined in an equation developed from the Framingham Heart Study to calculate prognosis. An online calculator is available at http://hp2010.nhlbihin.net/atpiii/calculator.asp.

Although many studies report better models than the Framingham model, the methods of these studies may not be adequate.[40]

A 2008 recalculation provides a calculator that includes diabetes mellitus as a risk factor.[41]

Asymptomatic adults should not be screened for coronary artery disease with an electrocardiogram.[42]

### Ankle brachial index (ABI)[edit]

For more information, see: Ankle brachial index.

A meta-analysis concluded that "measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS (Framingham risk score)".[35]

### Reynolds Score[edit]

The Reynolds score has been proposed as an improvement to the Framingham risk by incorporating the c-reactive protein.[43][38] The score has been validated in the Women's Genome Health Study.[44] An online calculator is at http://www.reynoldsriskscore.org/.

### C-reactive protein (CRP)[edit]

For more information, see: C-reactive protein.

The C-reactive protein may indicated risk in apparently healthy people due to the theory that chronic inflammation precedes atherosclerosis.[45]

The CRP is part of the Reynolds score.

## References[edit]

1. ↑ Anonymous (2025), 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. Summary at guidelines.gov
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. ↑ http://www.who.int/nutrition/topics/5_population_nutrient/en/index12.html
6. ↑ 6.0 6.1 U.S. Preventive Services Task Force (March 2009). "Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement". Ann. Intern. Med. 150 (6): 396–404. PMID 19293072. [e]
7. ↑ 7.0 7.1 7.2 Wolff T, Miller T, Ko S (March 2009). "Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. Preventive Services Task Force". Ann. Intern. Med. 150 (6): 405–10. PMID 19293073. [e]
8. ↑ Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M et al. (2012). "European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts).". Eur Heart J 33 (13): 1635-701. DOI:10.1093/eurheartj/ehs092. PMID 22555213. Research Blogging.
9. ↑ 9.0 9.1 Antithrombotic Trialists' (ATT) Collaboration. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J et al. (2009). "Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.". Lancet 373 (9678): 1849-60. DOI:10.1016/S0140-6736(09)60503-1. PMID 19482214. PMC PMC2715005. Research Blogging. Review in: Ann Intern Med. 2009 Sep 15;151(6):JC3-4, JC3-5 Review in: Evid Based Med. 2009 Dec;14(6):172-3
10. ↑ 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.
11. ↑ 11.0 11.1 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. DOI:10.1001/jama.295.3.306. PMID 16418466. Research Blogging.
12. ↑ 12.0 12.1 Algra A, Greving JP (May 2009). "Aspirin in primary prevention: sex and baseline risk matter". Lancet 373 (9678): 1821–2. DOI:10.1016/S0140-6736(09)61003-5. PMID 19482200. Research Blogging.
13. ↑ De Berardis G, Sacco M, Strippoli GF, Pellegrini F, Graziano G, Tognoni G et al. (2009). "Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials.". BMJ 339: b4531. DOI:10.1136/bmj.b4531. PMID 19897665. PMC PMC2774388. Research Blogging. Review in: Ann Intern Med. 2010 Apr 20;152(8):JC4-10
14. ↑ JAMA 2010 [Aspirin for Prevention of Cardiovascular Events in a General Population Screened for a Low Ankle Brachial Index]
15. ↑ Sung JJ, Lau JY, Ching JY, Wu JC, Lee YT, Chiu PW et al. (2010). "Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial.". Ann Intern Med 152 (1): 1-9. DOI:10.1059/0003-4819-152-1-201001050-00179. PMID 19949136. Research Blogging.
16. ↑ 16.0 16.1 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.
17. ↑ 17.0 17.1 Gissi-Hf Investigators (August 2008). "Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial". Lancet. DOI:10.1016/S0140-6736(08)61239-8. PMID 18757090. Research Blogging.
18. ↑ 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
19. ↑ 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
20. ↑ 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
21. ↑ Albert CM, Cook NR, Gaziano JM, et al (May 2008). "Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial". JAMA 299 (17): 2027–36. DOI:10.1001/jama.299.17.2027. PMID 18460663. Research Blogging.
22. ↑ Ebbing M, Bleie Ø, Ueland PM, et al (August 2008). "Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial". JAMA 300 (7): 795–804. DOI:10.1001/jama.300.7.795. PMID 18714059. Research Blogging.
23. ↑ Wang L, Manson JE, Song Y, Sesso HD (2010). "Systematic review: vitamin d and calcium supplementation in prevention of cardiovascular events.". Ann Intern Med 152 (5): 315-23. DOI:10.1059/0003-4819-152-5-201003020-00010. PMID 20194238. Research Blogging.
24. ↑ Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000). "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.". N Engl J Med 342 (3): 145-53. PMID 10639539.
25. ↑ Sleight P, Yusuf S, Pogue J, Tsuyuki R, Diaz R, Probstfield J et al. (2001 Dec 22-29). "Blood-pressure reduction and cardiovascular risk in HOPE study.". Lancet 358 (9299): 2130-1. DOI:10.1016/S0140-6736(01)07186-0. PMID 11784631. Research Blogging.
26. ↑ (2000) "Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators.". Lancet 355 (9200): 253-9. PMID 10675071.
27. ↑ Svensson P, de Faire U, Sleight P, Yusuf S, Ostergren J (2001). "Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy.". Hypertension 38 (6): E28-32. PMID 11751742.
28. ↑ Kurtz TW (2003). "False claims of blood pressure-independent protection by blockade of the renin angiotensin aldosterone system?". Hypertension 41 (2): 193-6. PMID 12574079.
29. ↑ Ogawa H, Nakayama M, Morimoto T, et al (November 2008). "Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial". JAMA 300 (18): 2134–41. DOI:10.1001/jama.2008.623. PMID 18997198. Research Blogging.
30. ↑ Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK (2006). "Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials.". Arch Intern Med 166 (21): 2307-13. DOI:10.1001/archinte.166.21.2307. PMID 17130382. Research Blogging. Review in: J Fam Pract. 2007 Mar;56(3):174
31. ↑ Ridker PM, Danielson E, Fonseca FA, et al (November 2008). "Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein". N. Engl. J. Med. 359 (21): 2195–207. DOI:10.1056/NEJMoa0807646. PMID 18997196. Research Blogging.
32. ↑ Gissi-HF Investigators, Tavazzi L, Maggioni AP, et al (October 2008). "Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial". Lancet 372 (9645): 1231–9. DOI:10.1016/S0140-6736(08)61240-4. PMID 18757089. Research Blogging.
33. ↑ León H, Shibata MC, Sivakumaran S, Dorgan M, Chatterley T, Tsuyuki RT (2008). "Effect of fish oil on arrhythmias and mortality: systematic review". BMJ 337: a2931. PMID 19106137. PMC 2612582. [e]
34. ↑ Wang TJ, Gona P, Larson MG, et al (December 2006). "Multiple biomarkers for the prediction of first major cardiovascular events and death". N. Engl. J. Med. 355 (25): 2631–9. DOI:10.1056/NEJMoa055373. PMID 17182988. Research Blogging.
35. ↑ 35.0 35.1 Fowkes FG, Murray GD, Butcher I, et al (July 2008). "Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis". JAMA 300 (2): 197–208. DOI:10.1001/jama.300.2.197. PMID 18612117. Research Blogging.
36. ↑ Polonsky TS, McClelland RL, Jorgensen NW, Bild DE, Burke GL, Guerci AD et al. (2010). "Coronary artery calcium score and risk classification for coronary heart disease prediction.". JAMA 303 (16): 1610-6. DOI:10.1001/jama.2010.461. PMID 20424251. Research Blogging.
37. ↑ Wilson, Peter W.F.; Michael Pencina, Paul Jacques, Jacob Selhub, Ralph D'Agostino, Christopher J. O'Donnell (2008-11-01). "C-Reactive Protein and Reclassification of Cardiovascular Risk in the Framingham Heart Study". Circ Cardiovasc Qual Outcomes 1 (2): 92-97. DOI:10.1161/CIRCOUTCOMES.108.831198. Retrieved on 2008-12-08. Research Blogging.
38. ↑ 38.0 38.1 Ridker PM, Paynter NP, Rifai N, Gaziano JM, Cook NR (November 2008). "C-reactive protein and parental history improve global cardiovascular risk prediction: the Reynolds Risk Score for men". Circulation 118 (22): 2243–51, 4p following 2251. DOI:10.1161/CIRCULATIONAHA.108.814251. PMID 18997194. Research Blogging.
39. ↑ Magnus P, Beaglehole R (2001). "The real contribution of the major risk factors to the coronary epidemics: time to end the "only-50%" myth". Arch. Intern. Med. 161 (22): 2657–60. PMID 11732929. [e]
40. ↑ (2009) Assessment of Claims of Improved Prediction Beyond the Framingham Risk Score. JAMA
41. ↑ D'Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM et al. (2008). "General cardiovascular risk profile for use in primary care: the Framingham Heart Study.". Circulation 117 (6): 743-53. DOI:10.1161/CIRCULATIONAHA.107.699579. PMID 18212285. Research Blogging.
42. ↑ Moyer VA, on behalf of the U.S. Preventive Services Task Force* (2012). "Screening for Coronary Heart Disease With Electrocardiography: U.S. Preventive Services Task Force Recommendation Statement.". Ann Intern Med. DOI:10.7326/0003-4819-157-7-201210020-00514. PMID 22847227. Research Blogging.
43. ↑ Ridker PM, Buring JE, Rifai N, Cook NR (February 2007). "Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score". JAMA 297 (6): 611–9. DOI:10.1001/jama.297.6.611. PMID 17299196. Research Blogging.
44. ↑ Paynter NP, Chasman DI, Buring JE, Shiffman D, Cook NR, Ridker PM (January 2009). "Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3". Ann. Intern. Med. 150 (2): 65–72. PMID 19153409. [e]
45. ↑ Lloyd-Jones DM, Liu K, Tian L, Greenland P. Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease. Ann Intern Med. 2006 Jul 4;145(1):35-42. PMID 16818927