info@biomedres.us   +1 (502) 904-2126   One Westbrook Corporate Center, Suite 300, Westchester, IL 60154, USA   Site Map
ISSN: 2574 -1241

Impact Factor : 0.548

  Submit Manuscript

Research ArticleOpen Access

Prevalence of Coronary Artery Disease in Patients with Peripheral Arterial Disease at the Hospital de Especialidades CMN La Raza” Volume 50- Issue 4

Carlos Sebastián Ficachi-Morales1*, Héctor Bizueto-Rosas2, Oscar Andrés Rodríguez-Jiménez3, Pablo Martín Boada-Sandoval1, Tayde Teresa Valdés-González4, Ángela Elena De Luna-Marmolejo1, Kemberly Valeria Hernández-Sotelo1, Josue Kadish Flores-Cuevas1, José Roberto Betanzos-Montes1, Víctor Adrián Pérez-Hernández1, Estrella Denisse Rosas-Zaragoza1, Noelly Noemí Bizueto-Blancas5, Andrea Velasco-Vázquez6 and Christian Varela-Román7

  • 1Resident of Vascular Surgery and Angiology, UMAE Hospital de Especialidades, Centro Médico Nacional “La Raza”, Mexican Institute of Social Security, Mexico
  • 2Department of Vascular Surgery and Angiology, “UMAE Hospital de Especialidades”, Centro Médico Nacional “La Raza”, Mexican Institute of Social Security, Mexico
  • 3Chief of Vascular Surgery and Angiology, UMAE Hospital de Especialidades, Centro Médico Nacional “La Raza”, Mexican Institute of Social Security, Mexico
  • 4Resident of General Surgery at Hospital General “Dr. Dario Fernandez Fierro” ISSSTE Mexico City, Mexico
  • 5Undergraduate Internal Medic. Saint Luke School of Medicine, Mexico City, Mexico
  • 6Vascular Surgeon, Department of Vascular Surgery and Angiology, General Hospital, Mexican Institute of Social Security, Pachuca Hgo. Mexico
  • 7Vascular Surgeon, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara Jal. Mexico

Received: May 13, 2023;   Published: May 31, 2023

*Corresponding author: Carlos Sebastián Ficachi-Morales, Department of Vascular Surgery and Angiology, “UMAE Hospital de Especialidades”, Centro Médico Nacional “La Raza”, Mexican Institute of Social Security, Mexico

DOI: 10.26717/BJSTR.2023.50.008000

Abstract PDF

ABSTRACT

Introduction: 60-80% of patients with peripheral arterial disease (PAD) of the lower extremities present with coronary artery disease (CAD); there are no reports in Mexico of said relationship. PAD is undervalued; also secondary to this, patients do not wander, causing patients with CAD to go undetected; In Mexican population, a high percentage of coronary arteries calcification has been identified, which altogether with predominant cardiovascular risk factors, makes it a priority to identify this association.
Objective: To establish the prevalence of CAD in patients with PAD.
Methods: An ambispective, descriptive, observational study was conducted to determine the prevalence of CAD diagnosed by Cardiology in patients with PAD, as well as associated comorbidities; diagnosing patients with PAD using the Ankle-Brachial index (ABI) ≤ 0.70. The results were analyzed with the statistical program SPSS-27.0.
Results: We collected 120 patients with PAD, with a predominance on females (72%); of these, 40/120 (33.3%) met the selection criteria; with an average age of 67 ± 9 years and a predominance of the male sex (75%); overweight 41%; diabetes and systemic arterial hypertension 65%; 37.5% (15/40) had severe coronary artery disease.
Conclusion: Even with the advances in molecular and histochemical medicine, it hasn’t been enough to reduce morbidity in cardiovascular diseases, so early detection of CAD is a priority.

Keywords: Coronary Artery Disease; Peripheral Arterial Disease; Prevalence; Cardiovascular Disease; Acute Coronary Syndrome

Abbreviations: PAD: Peripheral Arterial Disease; CAD: Coronary Artery Disease; ABI: Ankle-Brachial Index; AMI: Acute Myocardial Infraction; CAC: Coronary Artery Calcification; SMC: Smooth Muscle Cells

Introduction

Coronary artery disease (CAD) is mainly due to atherosclerosis; Atherosclerosis is a chronic and progressive process characterized by lipid and fibrous elements deposits in artery walls. It is the leading cause of morbidity and mortality in developed countries and is expected to be so in emerging countries. It manifests as a polyvascular disease (Figure 1) that affects more than one arterial territory, constituting an independent risk factor for mortality. It manifests itself more often in lower extremities (LE), so when we refer to peripheral arterial disease (PAD), we basically refer to this location. Location in LE is considered an independent risk marker for CAD [1]. CAD is common; some reports refer 40 to 60%, including up to 80% of patients with PAD; of these, 30% have severe CAD [2]. (Defined as one that affects three or more trunk coronary vessels or the left coronary artery.) The leading cause of death in patients with PAD is ischemic heart disease; 20% of patients with PAD are asymptomatic. Variations in Ancle brachial index (ABI) have been correlated with the severity and extent of CAD, as well as with the carotid mean intimate index (MIC); for every 0.1 decrease in ABI increases the risk of a major vascular event by 10% [3]. CAD etiology is considered multifactorial as in PAD, and it is associated with atherosclerosis, smoking, type 2 diabetes mellitus (DM2), systemic arterial hypertension (SAH) and dyslipidemia. The risk factors for PAD and CAD are similar, although their relative importance differs.

Figure 1.

biomedres-openaccess-journal-bjstr

Dyslipidemia is clearly associated with the development and progression of atherosclerosis; in particular, high serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are considered important factors in the onset and progression of PAD and CAD, with lipid-lowering medical therapy being the cornerstone of treatment [4]. In addition to the predominant comorbidities in our population, coronary arterial calcification (CAC) has been identified in 27% by computed tomography in our population with higher prevalence and magnitude in males with 40% [4]. As already mentioned, a considerable percentage of patients with PAD, have CAD; this is of utmost importance, since a high percentage of these patients, is underdiagnosed. Fortunately, we have a simple tool such as the Ankle-Brachial Index (ABI), which is much more sensitive when the degree of stenosis is higher and predictive of adverse events: the lower the ABI, the greater the risk of cardiovascular events[4,5].The mortality rate in patients with PAD averages 2% per year; for nonfatal acute myocardial infarction (AMI), stroke or vascular death is 5-7% per year [6]. ABI is a simple, inexpensive, non-invasive marker for PAD; a low ABI (≤0.9) is associated with a two-fold increased risk of CAD (AMI or angina) in general population (normal ABI >0.9- 1.3). According to international literature, the prevalence of low ABI in patients with auricular fibrillation is about 20%; the presence of asymptomatic PAD in this population was associated with a high risk of vascular events (defined as vascular death, fatal/nonfatal myocardial infarction, transient ischemic attack (TIA), fatal/nonfatal stroke) [7].

Coronary atherosclerosis is usually maintained for many years as a silent disease that does not cause any limitation or symptomatology during its development. When atherosclerotic lesions progress, they can narrow the vascular lumen, erode or rupture abruptly, causing the formation of a thrombus or clot that obstructs the arterial lumen, leaving a part of the heart muscle without irrigation [8]. According to various anatomopathological studies carried out in patients who died after an acute coronary syndrome (ACS), it is known that, although the atheromatous plaques responsible for acute ischemic events usually have a heterogeneous architecture and cellular composition, there are certain well-defined characteristics that differentiate these lesions from those found in patients with stable coronary heart disease (CHD). Thus, vulnerable plaques (plaques with thin fibrous layer, broad lipid nucleus and high inflammatory cells content) with significant inflammatory activity can erode and induce thrombosis or rapid progression of coronary lesion, causing an acute coronary event. Therefore, the best treatment is prevention of the disease, acting early on cardiovascular risk factors, in order to avoid or delay as much as possible the development of lesions [8]. Coronary atherosclerosis is the most common form of cardiovascular disease. Its clinical manifestations, such as AMI, angina pectoris and sudden death, constitute the leading cause of mortality in the adult population in developed countries.

Atherosclerotic lesions will progress or not depending on cardiovascular risk factors, genetics, environmental and biomechanical factors, causing various clinical manifestations of ischemic heart disease or CHD [8]. Smoking is of utmost importance, especially in our country, because tobacco occupies the fourth place in addictive substances consumed, and as evidenced in the Framingham study, a consumption around ten cigarettes a day, increases by 20% the risk of suffering from CHD in men and 23% in women. Similarly, for every 10 mg/dl increased in blood cholesterol levels, cardiovascular mortality increases by 9%; elevated blood pressure levels above 160/95 mmHg double or triple the risk of CHD, just as DM2 increases the risk of cardiovascular events in the same proportion. Genetic predisposition and advanced age are also mentioned [8]. It is also important to mention that PAD represents a risk factor in patients undergoing percutaneous coronary intervention procedures, since these patients have a lower success rate of the procedure and a higher rate of cardiovascular complications, including greater blood loss with the possibility of requiring transfusion, or even the need for surgical repair at the puncture local level, with longer surgical time and greater anesthetic risk [9].

Figure 2.

biomedres-openaccess-journal-bjstr

Etiology and Risk Factors

CAD occurs due to atherosclerosis that conditions stenotic or occlusive lesions of the arteries. When the endothelial function of the arterial wall is disturbed, atherosclerosis is initiated due to the accumulation of lipoprotein droplets in the intimate layer of the coronary vessels. High concentrations of LDL can permeate the altered endothelium and undergo oxidation. This oxidized or modified LDL (endocytosis) attracts leukocytes to the intimate layer of the coronary vessels, which can be phagocytosed by macrophages, leading to the formation of foam cells. These cells replicate and form lesions called fatty streaks (streaks of fats), which are the earliest form of atherosclerosis. The formation of such lesions triggers signals that attract smooth muscle cells (SMC) to the fatty stria location, initiating the proliferation and production of extracellular matrix, mainly compound by collagen and proteoglycans. Atherosclerotic plaque begins to develop, accumulating a large volume of extracellular matrix produced by SMC, leading to progression of the lesion to fibrous plaque (Figure 2). The fibrous plaque invades coronary vessel lumen and form small blood vessels which can subsequently calcify the plaques. The final lesion formed is an advanced and complicated lesion consisting of a fibrous covering with a lipid-rich core with necrotic, highly thrombogenic material [10]. Proteoglycans produced by SMC can bind to lipoproteins and prolong their existence in the intimate layer, making them susceptible to oxidative modifications and non-enzymatic conjugation with sugars (glycation).

Modified lipoproteins, i.e., oxidized phospholipids and advanced glycation end products can prolong the inflammatory response [10]. In the diagram below, we exemplify the evolution of atheromatous plaque in an artery transpolated to the coronary arteries as described by Malakar, et al. [10]. Matrix metalloproteinases (MMPs) are secreted by endothelial cells in response to oxidation, hemodynamic, inflammatory, and autoimmune signals. These MMPs, are in balance with endogenous tissue inhibitors and modulate various functions of vascular cells, such as activation, migration, proliferation, cell death, geometric remodeling, formation of new vessels, arterial and myocardial extracellular matrix destruction, and finally, healing. Programmed cell death or apoptosis commonly occurs in atherosclerotic lesions, which eventually leads to tissue factors degradation into the form of particles [11]. Stary, et al. in 2000 classified atherosclerotic lesions (adopted and revised by the American Heart Association) into eight types of lesion; following this line of classification, Dalager, et al. in 2007, compared atheromatous plaques present in coronary, carotid and femoral arteries; They found that femoral arteries had less presence of atheromatous plaques (20%); Herisson, et al. in 2011, compared carotid and femoral endarterectomy specimens, and found that femoral artery plaques contains less calcium, less cholesterol, and it is less inflamed.

These differences could have an explanation from the hemodynamic point of view given the characteristics of the flow in different anatomical territories, conditioning that the plaque has different properties and behaves differently depending on its environment and location [12]. In addition to the risk factors mentioned above for CAD, we should mention PAD as part of an important risk factor (ABI ≤ 0.9) [4,13].

Clinical Presentation

CAD may present as angina; An estimated 10 million people in the United States have angina; more than 500,000 new cases are diagnosed each year. The main cause of angina is an imbalance between the oxygen heart supply and demand, usually resulting from an atherosclerotic plaque narrowing or occluding the vessel [9,14]. Regarding PAD, its prevalence directly proportional increases significantly with age and it is to be expected that it will increase more and more due to population longevity. Lower extremities PAD is diagnosed when ABI is ≤ 0.90, as we had already mentioned (ABI results from dividing ankle systolic blood pressure by arm systolic blood pressure); in 2010, an estimated 202 million people worldwide had an ABI ≤ 0.90; Of these, almost 70% live in low and middle-income countries [13]. Most PAD carriers are asymptomatic. Claudication (fatigue, burning or pain in leg muscles), reproduces when exerting or walking and is relieved by rest. The pain location guides us to the site of the disease. Claudication is often difficult to identify to such an extent that there are several questionnaires to interrogate it, such as the Edinburgh questionnaire; there are several differential diagnoses in patients with exercise related LE pain. Critical limb ischemia is often resistant to opioid analgesia and can be difficult to distinguish from neuropathy. The patient refers to hanging the leg over the edge of the bed to relieve pain [15]. In a series of patients with PAD who underwent intracoronary vascular ultrasound examinations, more severe and rapidly progressive coronary atherosclerosis was demonstrated [4,6] than in patients with CAD without PAD.

Patients with CAD and PAD are at increased risk of future cardiovascular events, as PAD, regardless of type, is a strong predictor of poor outcomes in patients with CAD. The presence of PAD is associated with increased coronary atherosclerotic progression; The greater the number of PAD affected sites, the greater the risk of death in patients with CAD. For all associations, the identification of PAD as a prognostic marker in CAD risk stratification is justified [1,15,16].

Diagnostic Evaluation

A proper history and complete physical examination are essential in the diagnosis of PAD. However, several conditions associated with leg symptoms, such as a narrow spinal canal, osteoarthritis, chronic venous insufficiency and neuropathy, may be present and mask PAD and therefore not evidence a probable coronary problem.

Risk of Cardiovascular Events in PAD

PAD is associated with a high risk of CAD or CVD. The rates of myocardial infarction, ischemic stroke and vascular death in patients with LE PAD without critical ischemia are between 5-7% per year, being the most common causes of death CAD in 40-60% and stroke with 10%-20%. In patients with critical limb ischemia, the risk of death is 25% at 1 year [9]. In the diagnosis of PAD, ABI leisurely is the initial test recommended by the American Heart Association/ American College of Cardiology (AHA/ACC) Guideline [9,15,16].

Treatment

Mainly is to modify lifestyle and risk factors to reduce cardiovascular events and amputations in patients with PAD, being the principal approach to quit smoking and methodical walking [9,15-17]. Statins reduce cardiovascular risk; simvastatin was associated with reduced mortality from peripheral cardiovascular and vascular events. Other studies report that statin therapy reduces the progression of claudication, critical ischemia and the need for revascularization or amputation (Level of evidence I in the AHA/ ACC guideline) proprotein convertase subtilisin/kexin type 9 (PCSK9, an enzyme involved in the degradation of LDL receptors in the hepatocyte) bind blockers which act in LDL receptors, demonstrated the effectiveness of lipid-lowering therapy in patients with PAD [16]. On the other hand, the decrease in BP in patients with PAD with the use of ramipril, an inhibitor of the enzyme converting an of angiotensin (ACE-I), as reported in the Heart Outcomes Prevention Evaluation (HOPE) trial, was associated with a significant reduction in the presentation of AMI, stroke or cardiovascular death, independent of symptoms and ABI values. A retrospective analysis of data from the University of California at Davis PAD Registry showed that the use of ACE-I receptor blockers was associated with a significantly lower risk of cardiovascular, cerebrovascular, and mortality events in patients with critical limb ischemia [16,17].

Antiplatelet therapy as evidenced in CAPRIE study, which evaluated clopidogrel versus aspirin, a dosage of clopidogrel 75 mg/day, was associated with a 24% relative risk reduction in the combined risk of AMI, ischemic stroke, or vascular death compared with aspirin 325 mg a day dosage. In other clinical trials, patients with documented prior AMI, ischemic stroke, or symptomatic PAD had a significantly lower rate of cardiovascular death, with low-dose dual antiplatelet therapy [16,17]. The COMPASS (Anticoagulant and Aspirin in Stable Cardiovascular Disease) study demonstrated a major advance in atherosclerotic cardiovascular disease treatment [15-17]. CAD is present in patients with PAD in a high percentage (60 to 80%) and of these patients, 30% have severe coronary disease, however there are no reports in the national literature of the prevalence of this relationship. Therefore we set as objectives, to investigate, the prevalence of coronary heart disease in patients with PAD in C. M. N. La Raza patients in a study period from April 2022 to March 2023 being the main risk factor for coronary heart disease, taking as a reference that in our medical unit, LE PAD has a prevalence of 33%; being a high percentage of PAD underdiagnosed and therefore, patients with coronaropathy underdiagnosed.

In addition, considering that the Organization for Economic Cooperation and Development (OECD) issued a statement that our country ranks first in cardiovascular lethality (with a percentage greater than 30% against an average of 7.9% worldwide), in patients over 45 years of age, and since our medical unit has a captive population of more than 12 million entitled. Since Mexicans suffer from predisposing factors for cardiovascular events such as DM2, SAH, obesity, coronary calcification [4,15,18]. Our research is justified by the high socioeconomic impact of cardiovascular morbidity and mortality [15,19].

Graph 1.

biomedres-openaccess-journal-bjstr

Graph 2.

biomedres-openaccess-journal-bjstr

Graph 3.

biomedres-openaccess-journal-bjstr

Graph 4.

biomedres-openaccess-journal-bjstr

Graph 5.

biomedres-openaccess-journal-bjstr

Note: Source: Angiology Database, La Raza National Medical Center.

Graph 6.

biomedres-openaccess-journal-bjstr

Table 1. General characteristics of patients with CAD/PAD n=40 / N=120.

biomedres-openaccess-journal-bjstr

Note: Source: Database of the Angiology Service; La Raza National Medical Center.

Table 2. Diagnosis of PAD and location. N= 120.

biomedres-openaccess-journal-bjstr

Note: Source: Database of the Angiology Service, La Raza National Medical Center.
Abbreviations: Aorto-iliac disease AID, Femoro-popliteal disease FPD, Tibial Vessel Disease TVD.

Table 3. Diagnostic of CAD in patients with LE PAD (N= 120).

biomedres-openaccess-journal-bjstr

Table 4. Laboratory tests of patients with LEPAD (N = 120).

biomedres-openaccess-journal-bjstr

Note: Source: La Raza National Medical Center Clinical Archive.

Discussion

In a study conducted in our medical unit in 2019, to determine the prevalence of PAD in patients with ischemic heart disease, a prevalence of 36.9% was found in 225 patients; the most affected segment was the tibial vessels (53%), followed by the femoro-popliteus (27.7%); 24 In that study, patients admitted for CAD were looked for PAD; in our research, we studied patients who were hospitalized for PAD and found CAD. The above is very important, because it is described that in patients diagnosed with CAD and PAD, 30% have severe coronary heart disease, which CAD requires attention in the first place than PAD; and as we show in our research, the predominant lesions in more than 65%, are located in the femoro-popliteal segment and in the tibial vessels, most likely this implies that patients with PAD are underdiagnosed as well as patients with coronary artery disease, because they do not ambulate [23]. These locations surely influence the ambulation of patients, and with it, in cardiac manifestations.

There are no reports in Mexico of such a relationship; it is a priority to identify this association because of the high percentage CAC coupled with the predominant cardiovascular risk factors in our population.In relation to the population under 50 years of age, only 10% have coronary involvement; However, the diagnostic tools in these patients are deficient to assess the risks, and we must not forget that each time, atherosclerosis occurs in younger groups and in a more aggressive form [24,25]. Currently, the main problem is the necessity timely attention codes to detect and minimize the complications of pathologies that afflict developed and developing countries like ours; examples: heart attack code, brain code, to name a few. In our study, we detected CAD in 33.3% of patients with PAD who were admitted to our medical unit and who had no manifestations of this pathology. The importance of our research lies in the fact that it is described that ischemic cardiovascular diseases currently occupy the first places of morbidity and mortality in developed and developing countries, including, above oncological, traffic accidents and stroke, which is why the early diagnosis of CAD would allow us to achieve the prevention of acute ischemic attack and perform revascularization or appropriate medical management and thus reduce the morbidity and mortality and improve life quality of our population [26].

As we mentioned earlier, there are some unofficial reports that atherosclerosis behaves more aggressively in young people, so it would be very important to do more research to identify the role they play in this age population the miR-125a and miR-125b, identified in the arterial wall. Which play an important role in vascular pathogenesis that regulates vasoconstrictor gene expression and affects the synthesis and secretion of many vasoactive substances, which are associated with HDL (it is known that HDL has an important role in the innate and adaptive immune response, by modulating different components of the immune system); whereas the microRNA miR- 125b promotes atherosclerosis in coronary patients and therefore, investigate the therapeutic potential of suppressing miR-125 in vivo [27]. Even though in our country the population pyramid is being inverted, there are reports of cardiovascular mortality since the 90’S of 33.4% in the population of 15-64 years, a fraction of the economically active population [28]. On the other hand, we must not forget that in our population it was found in 27% CAC, with predominance in the male sex (40%) and more severe [4]. In Latin America, mortality from coronary heart disease is increasing, and a 20% increase is expected for the 20’s. Cardiovascular diseases represent 25% of all diseases aged 60 years and over, a prevalence that increases with age.

The fact that in our research we have found that the prevalence of CAD predominates mainly in patients with Rutherford category 5 (minor tissue loss), makes us think that we are detecting it late (in more advanced stages) then we must focus on preventive studies, practice preventive medicine and not only curative. In addition, our research showed that we are above international reports in terms of the severe coronary artery disease frequency in patients with PAD (37.5% vs 30%), surely, these results are influenced by the pathologies that afflict us (DM2, obesity, CAC). The frequency of presentation by gender in coronary heart disease was reversed with a predominance in male gender 3:1 (Graph 1).

Conclusion

Advances in molecular and histochemical medicine have not been sufficient to reduce the morbidity and mortality of cardiovascular diseases, so it is a priority to detect CAD early [29,30]. The diagnosis of coronary artery disease allows preventive measures to be taken to avoid complications and to establish a level of priority of the procedures to be carried out. The comorbidities that afflict our population influenced coronary disease.

Conflict of Interest

Authors declare no conflict interest.

References

  1. Niamkey JT, Yao H, Matanga J, Ekou A, Kouamé I, et al. (2021) Évaluation des lésions artérielles périphériques chez le coronarien avéré à l'Institut de cardiologie d'Abidjan en Côte d'Ivoire [Assessment of peripheral artery disease in proven coronary patients in Abidjan Heart Institute of Côte d'Ivoire]. Ann Cardiol Angeiol (Paris) 70(1): 13-17.
  2. Kappetein AP, Dawkins KD, Mohr FW, Morice MC, Mack MJ, et al. (2006) Current percutaneous coronary intervention and coronary artery bypass grafting practices for three-vessel and left main coronary artery disease. Insights from the SYNTAX run-in phase. European journal of cardio-thoracic surgery 29(4): 486-491.
  3. Mehler PS, Coll JR, Estacio R, Esler A, Schrier RW, et al. (2003) Intensive blood pressure control reduces the risk of cardiovascular events in patients with peripheral arterial disease and type 2 diabetes. Circulation 107(5): 753-756.
  4. Bonacchi M, Parise O, Matteucci F, Tetta C, Moula AI, et al. (2020) Is Peripheral Artery Disease an Independent Predictor of Isolated Coronary Artery Bypass Outcome? Heart Lung Circ 29(10): 1502-1510.
  5. Khan N, Khan J, Lyytikäinen LP, Lehtimäki T, Laurikka J, et al. (2020) Serum apolipoprotein A-I concentration differs in coronary and peripheral artery disease. Scand J Clin Lab Invest 80(5): 370-374.
  6. Posadas-Romero C, López-Bautista F, Rodas-Díaz MA, Posadas-Sánchez R, Kimura-Hayama E, et al. (2017) Prevalence and extent of coronary artery calcification in asymptomatic cardiovascular Mexican population: Genetic study of atherosclerotic disease. Arch Cardiol Mex 87(4): 292-301.
  7. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, et al. (2007) Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease. EJVES 33(Suppl 1): 9-11.
  8. Fernandez Ortiz A (2009) What is coronary arteriosclerosis. In: López-Farré A, Macaya-Miguel C, editores: Libro de la salud cardiovascular del Hospital Clínico San Carlos III y la fundación BBVA, Spain: Editorial Nerea chap 26: 241-249.
  9. Song P, Rudan D, Zhu Y, Fowkes FJI, Rahimi K, et al. (2019) Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: An updated systematic review and analysis. Lancet Glob Health 7(8): E1020-E1030.
  10. Kojima K, Kimura S, Hayasaka K, Mizusawa M, Misawa T, et al. (2019) Aortic Plaque Distribution, and Association between Aortic Plaque and Atherosclerotic Risk Factors: An Aortic Angioscopy Study. J Atheroscler Thromb 26(11): 997-1006.
  11. González Pacheco H (2006) From the thrombin hypothesis to inflammation. Is it a reality? Arch Cardiol. Mex magazine on the Internet 76(Suppl2): 233-238.
  12. Pérez González HA, Bizueto Rosas H, Esquinca Moreno BH, Baeza Galván BI, Flores Izar FJ, et al. (2016) Complications of the residual limb after supracondylar amputation. Rev Mex Angiol 44(2): 53-59.
  13. Kloner RA, Chaitman B (2017) Angina and Its Management. J Cardiovasc Pharmacol Ther 22(3): 199-209.
  14. Morley RL, Sharma A, Horsch AD, Hinchliffe RJ (2018) Peripheral artery disease. BMJ 360: j5842.
  15. Manfrini O, Amaduzzi PL, Cenko E, Bugiardini R (2018) Prognostic implications of peripheral artery disease in coronary artery disease. Curr Opin Pharmacol 39: 121-128.
  16. Campia U, Gerhard Herman M, Piazza G, Goldhaber SZ (2019) Peripheral Artery Disease: Past, Present, and Future. Am J Med 132(10): 1133-1141.
  17. Bauersachs R, Zeymer U, Brière JB, Marre C, Bowrin K, et al. (2019) Burden of Coronary Artery Disease and Peripheral Artery Disease: A Literature Review. Cardiovasc Ther 2019: 8295054.
  18. OECD (2015) Cardiovascular Disease and Diabetes: Policies for Better Health and Quality of Care, OECD Health Policy Studies, OECD Publishing, Paris.
  19. Serruys PW, Morice MC, Kappetein AP, Coombo A, Holmes DR, et al. (2009) Percutaneous Coronary Intervention versus Coronary-Artery Bypass Grafting for Severe Coronary Artery Disease. N Engl Med 360(10): 961-972.
  20. (2022) World Medical Association Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects.
  21. General Health Law. TITLE FIFTH. Research for health, single chapter.
  22. (2009) Ministry of Health. Official Mexican Standard NOM-012-SSA3-2012, which establishes the criteria for the execution of research projects for health in human beings. Mexico.
  23. Mejía Espinoza RA (2020) Prevalence of Peripheral Arterial Disease in Patients with Ischemic Heart Disease (degree thesis). Mexican Institute of Social Security, Mexico City, Mexico.
  24. Sniderman AD, Furberg CD (2008) Age as a modifiable risk factor for cardiovascular disease. Lancet 371: 1547-1549.
  25. Doval HC (2015) Is Cardiovascular Risk Prediction Fact or Fiction Treating the at-risk patient or the at-risk population? Rev Argent Cardiol 83: 490-497.
  26. Moro Rodríguez RT, Valdés Cantero JL, Olivera DR, Fuentes Valdés L, Mirabal Rodríguez R (2022) Arteriosclerotic carotid lesion in patients with coronary surgery. Revista Cubana de Angiología y Cirugía Vascular 23(3): e387.
  27. Hueso M, Griñán R, Mallen A, Navarro E, Purqueras E, et al. (2022) MiR-125b downregulates macrophage scavenger receptor type B1 and reverse cholesterol transport. Biomed Pharmacother 146: 112596.
  28. Navarro Robles J (1999) Problematic of atherosclerosis in Mexico. Rev Mex Cardiol 10(2): 59-63.
  29. Zárate Treviño A, Manuel Apolinar L, Basurto L, De la Chesnaye E, Saldívar I, et al. (2016) Cholesterol and atherosclerosis. Historical considerations and treatment. Arch Cardiol Mex 86(2): 163-169.
  30. Martínez Blanco Delio Felipe (2019) Arteriographic pattern and morbidity and mortality of atherosclerotic lesions of lower limbs in the beneficiaries of the "Doctor Antonio Fraga Mouret" Specialty Hospital. (thesis). Mexican Institute of Social Security, Mexico City, Mexico.