New Cardiovascular Risk Screening Strategy.

Peripheral Artery Disease Clinical Trial

— HELENA  

Official title:

Health Program for prEvention of cardiovascuLar disEases Based on a Risk screeNing Strategy With Ankle-brachial Index.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05884840
• Other study ID #: SLT/21/000015
• Status: Recruiting
• Phase: N/A
• Start date: November 20, 2023
• Est. completion date: June 2026

Study information

• Verified date: December 2023
• Source: Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina
• Contact: Rafel Ramos Blanes, MD, PhD
• Phone: +34 972 48 79 68
• Email: rramos.girona.ics[@]gencat.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Mortality due to cardiovascular disease (CVD) in Spain accounted for 29% of all deaths (32% in women and 26% in men) in 2017. Out of those, 67% were related to a coronary or a cerebrovascular disease .

A key strategy in primary prevention of CVD is to use risk functions to individualize preventive interventions for each patient. The current CV risk-screening program in some regions of Spain, is based using an adapted Framingham scale, REGICOR's risk function, which is integrated in the primary care electronic health record. This risk function predicts the probability within 10 years of developing a coronary event. However, this function fails to identify patients that fall into low- or intermediate-risk level, and might develop a CV event in the up following 10 years.

Ankle-brachial index (ABI) is a simple, non-invasive and economic technique, which allows detecting peripheral arterial disease (PAD), and gives independent risk function information compared to other coronary risk functions. Even tough, between 13-27% of middle age population have an ABI ≤ 9, around 50-89% of them do not exhibit any symptoms. However, they hold higher mortality risk and CV events. Current clinical guidelines for PAD screening, have a limited level of evidence, and only recommend using ABI on patients aged 50-70, who have diabetes or are smokers, and patients older than 70 years old.

A new risk function, REASON, to assess CVD risk has been designed. This model has proven to improve predictive capacity of holding an ABI ≤ 0.9 on those patients aged 50-74 that are apparently free of CVD. Therefore, a strategy that combines the current CV risk estimation using REGICOR, and the prediction capacity of pathologic ABI with REASON, would allow detecting high-risk patients with a PAD screening program. It is possible that patients, who hold an ABI ≤ 0.9, even if being asymptomatic, will adopt physician's recommendations on healthy life habits and preventive treatment.

The aims of this study are:

• To assess the effectiveness and cost-utility of adding a screening program with ABI to the current strategy of CV risk detection to reduce the incidence of CVD and mortality from all causes in the population aged 50 to 74.

• To assess the effectiveness of adding a screening program with ABI to the current strategy of CV risk detection to improve cardiovascular risk factors in the population aged 50 to 74.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54000
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 74 Years

Eligibility

Inclusion Criteria:

• Patients aged 50 to 74, which are free or do not have previous history of CVD. Patients that hold a REGICOR CV risk score =7, and REASON risk core =7, during a routine primary care visit

Exclusion Criteria:

• Symptomatic PAD

• Coronary disease

• Stroke

• Cardiac revascularization

Related Conditions & MeSH terms

• Arteriosclerosis
• Asymptomatic
• Cardiovascular Prevention
• Peripheral Arterial Disease
• Peripheral Artery Disease
• Screening

Intervention

Diagnostic Test:
• HELENA
The current CV risk screening program in based using the REGICOR risk function, which is integrated in the primary care electronic health record. This risk function predicts the probability within 10 years of developing a coronary event. Those who are categorized as high risk, obtaining a 10% of probability, are candidates of receiving lipid lowering drugs and recommendations on healthy life habits. What this intervention suggests is that, besides the REGICOR estimation, the electronic health records will also incorporate a new CV risk function, REASON. The model predicts the risk of holding a pathologic ABI score, in people aged 50-74 years old who are apparently free of CV. Patients who obtain a score = 7 will undergo a PAD screening program with ABI test. If the value of the test is =0.9, the REGICOR, physicians will recommend indications of the Health Catalan Institute's CV and lipid Guidelines to the patients.

Locations

Country	Name	City	State
Spain	Institut Català de la Salut (ICS)	Barcelona

Sponsors (5)

Lead Sponsor	Collaborator
Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina	Biocruces Bizkaia Health Research Institute, Hospital del Mar Research Institute (IMIM), Institut Català de la Salut, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta

Country where clinical trial is conducted

Spain, 

References & Publications (21)

Ankle Brachial Index Collaboration; Fowkes FG, Murray GD, Butcher I, Heald CL, Lee RJ, Chambless LE, Folsom AR, Hirsch AT, Dramaix M, deBacker G, Wautrecht JC, Kornitzer M, Newman AB, Cushman M, Sutton-Tyrrell K, Fowkes FG, Lee AJ, Price JF, d'Agostino RB, Murabito JM, Norman PE, Jamrozik K, Curb JD, Masaki KH, Rodriguez BL, Dekker JM, Bouter LM, Heine RJ, Nijpels G, Stehouwer CD, Ferrucci L, McDermott MM, Stoffers HE, Hooi JD, Knottnerus JA, Ogren M, Hedblad B, Witteman JC, Breteler MM, Hunink MG, Hofman A, Criqui MH, Langer RD, Fronek A, Hiatt WR, Hamman R, Resnick HE, Guralnik J, McDermott MM. Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. JAMA. 2008 Jul 9;300(2):197-208. doi: 10.1001/jama.300.2.197. — View Citation

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Comin E, Solanas P, Cabezas C, Subirana I, Ramos R, Gene-Badia J, Cordon F, Grau M, Cabre-Vila JJ, Marrugat J. [Estimating cardiovascular risk in Spain using different algorithms]. Rev Esp Cardiol. 2007 Jul;60(7):693-702. Spanish. — View Citation

Diederichsen AC, Rasmussen LM, Sogaard R, Lambrechtsen J, Steffensen FH, Frost L, Egstrup K, Urbonaviciene G, Busk M, Olsen MH, Mickley H, Hallas J, Lindholt JS. The Danish Cardiovascular Screening Trial (DANCAVAS): study protocol for a randomized controlled trial. Trials. 2015 Dec 5;16:554. doi: 10.1186/s13063-015-1082-6. — View Citation

Espinola-Klein C, Rupprecht HJ, Bickel C, Lackner K, Savvidis S, Messow CM, Munzel T, Blankenberg S; AtheroGene Investigators. Different calculations of ankle-brachial index and their impact on cardiovascular risk prediction. Circulation. 2008 Aug 26;118(9):961-7. doi: 10.1161/CIRCULATIONAHA.107.763227. Epub 2008 Aug 12. — View Citation

Greenland P, Abrams J, Aurigemma GP, Bond MG, Clark LT, Criqui MH, Crouse JR 3rd, Friedman L, Fuster V, Herrington DM, Kuller LH, Ridker PM, Roberts WC, Stanford W, Stone N, Swan HJ, Taubert KA, Wexler L. Prevention Conference V: Beyond secondary prevention: identifying the high-risk patient for primary prevention: noninvasive tests of atherosclerotic burden: Writing Group III. Circulation. 2000 Jan 4;101(1):E16-22. doi: 10.1161/01.cir.101.1.e16. No abstract available. — View Citation

Grewal J, Anand S, Islam S, Lonn E; SHARE and SHARE-AP Investigators. Prevalence and predictors of subclinical atherosclerosis among asymptomatic "low risk" individuals in a multiethnic population. Atherosclerosis. 2008 Mar;197(1):435-42. doi: 10.1016/j.atherosclerosis.2007.06.020. Epub 2007 Aug 6. — View Citation

Heald CL, Fowkes FG, Murray GD, Price JF; Ankle Brachial Index Collaboration. Risk of mortality and cardiovascular disease associated with the ankle-brachial index: Systematic review. Atherosclerosis. 2006 Nov;189(1):61-9. doi: 10.1016/j.atherosclerosis.2006.03.011. Epub 2006 Apr 18. — View Citation

Institute for Health Metrics and Evaluation. Global Burden of Disease Results Tool, Global Health Data Exchange. 2017

Lindholt JS, Sogaard R. Population screening and intervention for vascular disease in Danish men (VIVA): a randomised controlled trial. Lancet. 2017 Nov 18;390(10109):2256-2265. doi: 10.1016/S0140-6736(17)32250-X. Epub 2017 Aug 28. — View Citation

McDermott MM, Greenland P, Liu K, Guralnik JM, Celic L, Criqui MH, Chan C, Martin GJ, Schneider J, Pearce WH, Taylor LM, Clark E. The ankle brachial index is associated with leg function and physical activity: the Walking and Leg Circulation Study. Ann Intern Med. 2002 Jun 18;136(12):873-83. doi: 10.7326/0003-4819-136-12-200206180-00008. Erratum In: Ann Intern Med. 2003 Aug 19;139(4):306. — View Citation

Ministerio de Sanidad SS e I. Indicadores de Salud 2020 Evolución de los indicadores del estado de salud en España y su magnitud en el contexto de la Unión Europea. Madrid; 2020.

Morrow DA, de Lemos JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation. 2007 Feb 27;115(8):949-52. doi: 10.1161/CIRCULATIONAHA.106.683110. No abstract available. — View Citation

Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG; TASC II Working Group; Bell K, Caporusso J, Durand-Zaleski I, Komori K, Lammer J, Liapis C, Novo S, Razavi M, Robbs J, Schaper N, Shigematsu H, Sapoval M, White C, White J, Clement D, Creager M, Jaff M, Mohler E 3rd, Rutherford RB, Sheehan P, Sillesen H, Rosenfield K. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg. 2007;33 Suppl 1:S1-75. doi: 10.1016/j.ejvs.2006.09.024. Epub 2006 Nov 29. No abstract available. — View Citation

Perlstein TS, Creager MA. The ankle-brachial index as a biomarker of cardiovascular risk: it's not just about the legs. Circulation. 2009 Nov 24;120(21):2033-5. doi: 10.1161/CIRCULATIONAHA.109.907238. Epub 2009 Nov 9. No abstract available. — View Citation

Ramos R, Baena-Diez JM, Quesada M, Solanas P, Subirana I, Sala J, Alzamora M, Fores R, Masia R, Elosua R, Grau M, Cordon F, Pera G, Rigo F, Marti R, Ponjoan A, Cerezo C, Brugada R, Marrugat J. Derivation and validation of REASON: a risk score identifying candidates to screen for peripheral arterial disease using ankle brachial index. Atherosclerosis. 2011 Feb;214(2):474-9. doi: 10.1016/j.atherosclerosis.2010.11.015. Epub 2010 Nov 19. — View Citation

Ramos R, Garcia-Gil M, Comas-Cufi M, Quesada M, Marrugat J, Elosua R, Sala J, Grau M, Marti R, Ponjoan A, Alves-Cabratosa L, Blanch J, Bolibar B. Statins for Prevention of Cardiovascular Events in a Low-Risk Population With Low Ankle Brachial Index. J Am Coll Cardiol. 2016 Feb 16;67(6):630-640. doi: 10.1016/j.jacc.2015.11.052. — View Citation

Ramos R, Quesada M, Solanas P, Subirana I, Sala J, Vila J, Masia R, Cerezo C, Elosua R, Grau M, Cordon F, Juvinya D, Fito M, Isabel Covas M, Clara A, Angel Munoz M, Marrugat J; REGICOR Investigators. Prevalence of symptomatic and asymptomatic peripheral arterial disease and the value of the ankle-brachial index to stratify cardiovascular risk. Eur J Vasc Endovasc Surg. 2009 Sep;38(3):305-11. doi: 10.1016/j.ejvs.2009.04.013. Epub 2009 Jun 10. — View Citation

US Preventive Services Task Force; Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, Davidson KW, Doubeni CA, Epling JW Jr, Kemper AR, Kubik M, Landefeld CS, Mangione CM, Silverstein M, Simon MA, Tseng CW, Wong JB. Screening for Peripheral Artery Disease and Cardiovascular Disease Risk Assessment With the Ankle-Brachial Index: US Preventive Services Task Force Recommendation Statement. JAMA. 2018 Jul 10;320(2):177-183. doi: 10.1001/jama.2018.8357. — View Citation

Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Back M, Benetos A, Biffi A, Boavida JM, Capodanno D, Cosyns B, Crawford C, Davos CH, Desormais I, Di Angelantonio E, Franco OH, Halvorsen S, Hobbs FDR, Hollander M, Jankowska EA, Michal M, Sacco S, Sattar N, Tokgozoglu L, Tonstad S, Tsioufis KP, van Dis I, van Gelder IC, Wanner C, Williams B; ESC National Cardiac Societies; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337. doi: 10.1093/eurheartj/ehab484. No abstract available. Erratum In: Eur Heart J. 2022 Nov 7;43(42):4468. — View Citation

Wilkins E, et al. European Cardiovascular Disease Statistics. European Heart Network, editor. Brussels; 2017

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hard coronary heart disease (CHD)	Myocardial infarction, cardiac revascularization, or coronary death	3 years
Primary	Major adverse cardiovascular event (MACE)	A composite of hard CHD (myocardial infarction, cardiac revascularization, or coronary death) and stroke (fatal and nonfatal ischemic stroke)	3 years
Primary	All-cause mortality		3 years
Primary	Tabaco consumption (CVD risk factors improvement assessment)	Smoker, ex-smoker or non-smoker	3 years
Primary	Lipid profile (CVD risk factors improvement assessment)	Total cholesterol (mg/dl), LDL (mg/dl), HDL (mg/dl), Triglycerides (mg/dl)	3 years
Primary	Systolic and diastolic pressure (CVD risk factors improvement assessment)	mm Hg	3 years
Primary	Weight (CVD risk factors improvement assessment)	kg	3 years
Primary	Height (CVD risk factors improvement assessment)	m	3 years
Primary	BMI (CVD risk factors improvement assessment)	(kg/m2) Will be calculated dividing the weight in kilograms by their height in metres squared	3 years
Primary	Glycaemia (CVD risk factors improvement assessment)	Fasting blood sugar (mg/dl)	3 years
Primary	Glycated haemoglobin (CVD risk factors improvement assessment)	(in DM patients) glycosylated hemoglobin in the blood (mg/dl) or percentage (%)	3 years
Primary	Creatinine (CVD risk factors improvement assessment)	mg/dL	3 years
Primary	Proteinuria (CVD risk factors improvement assessment)	mg/dL protein in urine	3 years
Primary	Albumin-to-creatinine ratio (ACR) (CVD risk factors improvement assessment)	ACR (mg/g) will be calculated by by dividing mg of proteinuria (albumine) by g of creatinine.	3 years
Primary	Glomerular filtrate rate (CVD risk factors improvement assessment)	Levels of creatinine in milliliters of cleansed blood per minute per body surface (mL/min/1.73m2).	3 years
Secondary	Coronary heart disease	A composite of angina and hard CHD	3 years
Secondary	Cerebrovascular disease	A composite of stroke (fatal and nonfatal ischemic stroke) and transient ischemic attack	3 years
Secondary	Cardiovascular disease	a composite of MACE, angina and transient ischemic attack	3 years
Secondary	Lipid lowering medication Adverse effects	1) Short-term effects: Muscular and hepatic alterations, and 2) long-term effects: Diabetes and cancer	3 years