Journal of Clinical Medicine Article Prevalence of Peripheral Arterial Disease and Associated Vascular Risk Factors in 65-Years-Old People of Northern Barcelona Gabriela Gonçalves-Martins 1,2 , Daniel Gil-Sala 1, * , Cristina Tello-Díaz 1 , Xavier Tenezaca-Sari 1 , Carlos Marrero 1 , Teresa Puig 3,4 , Raquel Gayarre 5,6 , Joan Fité 7 and Sergi Bellmunt-Montoya 1,2 1 Angiology, Vascular and Endovascular Surgery Department, Hospital Vall d’Hebron, 08035 Barcelona, Spain; ggoncalves@vhebron.net (G.G.-M.); cristina.tello11@gmail.com (C.T.-D.); atenezaca@vhebron.net (X.T.-S.); cmarrero@vhebron.net (C.M.); sbellmunt@vhebron.net (S.B.-M.) 2 Departament de Cirurgia, Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain 3 Department of Clinical Epidemiology and Public Health, Hospital de la Santa Creu i Sant Pau. IIB Sant Pau, 08041 Barcelona, Spain; tpuig@santpau.cat 4 Deparment of Pediatrics, Obstetrics and Gynecology and Preventive Medicine, Universitat Autònoma de Barcelona (UAB), CIBERCV. 08035, Barcelona, Spain 5 Primary Care Department, Institut Català de la Salut, 08041 Barcelona, Spain; rgayarre@gencat.cat 6 Departament de Medicina, Unitat Docent Sant Pau, Universitat Autònoma de Barcelona (UAB), 08025 Barcelona, Spain  7  Angiology, Vascular and Endovascular Surgery Department, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Biomèdica de Sant Pau (IIB-Sant Pau), CIBERCV, 08041 Barcelona, Spain; jfite@santpau.cat Citation: Gonçalves-Martins, G.; * Correspondence: dgil@vhebron.net; Tel.: +34-93-2746131 Gil-Sala, D.; Tello-Díaz, C.; Tenezaca-Sari, X.; Marrero, C.; Puig, Abstract: Objective: To determine the prevalence and risk factors associated with peripheral arterial T.; Gayarre, R.; Fité, J.; disease (PAD) in Northern Barcelona at 65 years of age. Methods: A single-center, cross-sectional Bellmunt-Montoya, S. Prevalence of study, including males and females 65 years of age, health care cardholders of Barcelona Nord. Peripheral Arterial Disease and PAD was defined as an ankle–brachial index (ABI) < 0.9. Attending subjects were evaluated for a Associated Vascular Risk Factors in 65-Years-Old People of Northern history of common cardiovascular risk factors. A REGICOR score was obtained, as well as a physical Barcelona. J. Clin. Med. 2021, 10, 4467. examination and anthropometric measurements. Results: From November 2017 to December 2018, https://doi.org/10.3390/jcm10194467 1174 subjects were included: 479 (40.8%) female and 695 (59.2%) male. Overall prevalence of PAD was 6.2% (95%CI: 4.8–7.6%), being 7.9% (95%CI: 5.9–9.9%) in males and 3.8% (95%CI: 2.1–5.5%) in females. Academic Editors: An independent strong association was seen in male smokers and diabetes, with ORs pf 7.2 (95% CI: Christian-Alexander Behrendt and 2.8–18.6) and 1.8 (95% CI: 1.0–3.3), respectively, and in female smokers and hypertension, with ORs Frederik Peters of 5.2 (95% CI: 1.6–17.3) and 3.3 (95% CI: 1.2–9.0). Male subjects presented with higher REGICOR scores (p < 0.001). Conclusion: Higher-risk groups are seen in male subjects with a history of smoking Received: 29 August 2021 and diabetes and female smokers and arterial hypertension, becoming important subgroups for our Accepted: 24 September 2021 primary healthcare centers and should be considered for ABI screening programs. Published: 28 September 2021 Keywords: peripheral arterial disease; cardiovascular risk factors; asymptomatic; ankle–brachial Publisher’s Note: MDPI stays neutral index; prevalence; screening with regard to jurisdictional claims in published maps and institutional affil- iations. 1. Introduction Peripheral arterial disease (PAD) is the manifestation of atherosclerotic disease in Copyright: © 2021 by the authors. the lower extremities, resulting in narrowing of the blood vessels and diminishing blood Licensee MDPI, Basel, Switzerland. flow to the limbs. It is the third leading cause of cardiovascular pathology after coronary This article is an open access article and cerebrovascular disease and an important indicator of cardiovascular risk [1]. The distributed under the terms and mere presence of PAD can indicate a 6.6-fold increased risk of cardiovascular disease conditions of the Creative Commons association [2], becoming, therefore, an important indicator of the coexistence of other Attribution (CC BY) license (https:// cardiovascular pathologies. creativecommons.org/licenses/by/ Associated risk factors are common for cardiovascular diseases, such as smoking, 4.0/). diabetes, dyslipidemia and hypertension, among others. Active smoking has the strongest J. Clin. Med. 2021, 10, 4467. https://doi.org/10.3390/jcm10194467 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, 4467 2 of 11 association, doubling the risk of PAD in these patients [3]. Therefore, early diagnosis and treatment of modifiable risk factors is an important tool in preventing and treating this disease, consequently lowering associated cardiovascular disease morbidity and mortality. The ankle–brachial index (ABI) is an effective, easy and first-line noninvasive method in screening PAD [4–6], with an overall 69–79% sensitivity and 83–99% specificity for detecting >50% arterial stenosis [7]. Despite the feasibility of this technique, this pathology is well known to be underdiagnosed and undertreated [4,5]. In the United States, 8 to 12 million Americans suffer from PAD, with an overall prevalence of 3–10%, which increases to almost 50% in those greater than 85 years old [8,9]. As for Europe, prevalence as high as 17.8% (99% CI: 16.84–18.83%) was observed in some studies, especially in the northern region [10]. PAD is also influenced by gender and age, predominantly being associated with the male gender. Age is also an important factor, with a 20% increase observed in those older than 75 [11,12]. In a global aging society, this can present an important social and economic burden. To our knowledge, most studies focused on the prevalence of PAD performed in our region were inclusive of younger age groups, some including ages as young as 35 years old [13,14]. This perhaps explains the low prevalence results achieved in these studies. Due to the important variety of factors that influence the prevalence of this pathology, age being one of them, we decided to perform a study including individuals of 65 years old in order to analyze if an increase of prevalence was seen in these groups and, as such, evaluate if there were differences in our gender groups with this increase in age, as well as associated risk factors. This way perhaps allows pinpointing a target group that requires a more detailed initial evaluation and opportunistic screening (with ABI) in our primary care centers in order to prevent and/or diagnose PAD. Thus, the aim of our study was to determine the prevalence of peripheral arterial disease through ABI in 65-year-old men and women in Northern Barcelona (Spain), as well as its associated risk factors. 2. Materials and Methods This is a single-center, populational-based, cross-sectional study, part of a larger pilot screening program evaluating abdominal aorta aneurysm [15]. The protocol was approved by the ethics committee of Hospital Vall d’Hebron with code PR(AG)221/2017. 2.1. Patient Selection The study was carried out in a health-integrated area AIS-Barcelona Nord, with a population base of 400,000 inhabitants, which corresponds to the area of treatment of our center. Inclusion criteria were all noninstitutionalized males and females of 65 years of age during the time of recruitment who were health care cardholders and resided for at least 6 months in the referred area. Contact information of the population was authorized and obtained through our public health census registry, and all eligible subjects received invitation letters informing them of the present study and tests to be performed. Those with incorrect postal data, terminal disease and deceased subjects were considered ineligible (Figure 1). Nonresponders to the first letter were invited again within 1 month. Those who agreed to participate were scheduled an appointment at our Vascular Lab Center with one of five trained vascular surgeon residents. Participants were contacted 48 h before the appointment to confirm attendance. Those who did not show up for the scheduled appointment after 3 occasions, those who did not wish to participate and subjects who did not respond to both invitation letters were excluded. J. Clin. J. Clin. Med.Med. 10, x10, 2021,2021, FOR4467 PEER REVIEW 3 of 312of 11 Figure Figure 1. Flowchart 1. Flowchart of initial of initial inclusion inclusion description. description. 2.2. Variables Evaluated Nonresponders to the first letter were invited again within 1 month. Those who After arrival, prior to questioning, a signed consent form was required from each agreed to participate were scheduled an appointment at our Vascular Lab Center with one participant. All subjects were questioned for a history of risk factors, such as: cigarette of five trained vascular surgeon residents. Participants were contacted 48 h before the ap- smoking: active, former (more than a year without smoking) or nonsmoker; hypertension, pointment to confirm attendance. Those who did not show up for the scheduled appoint- defined as systolic blood pressure ≥140/90 mmHg or subjects under antihypertensive ment after 3 occasions, those who did not wish to participate and subjects who did not treatment; dyslipidemia, defined as one or all of total blood cholesterol >200 mg/dL, low- respond to both invitation letters were excluded. density lipoprotein (LDL) cholesterol >100 mg/dL or triglycerides >150 mg/dL or subjects under treatment for dyslipidemia; diabetes, defined as those diagnosed and/or under 2.2. Variables Evaluated antidiabetic treatment; history of cerebrovascular disease (previous stroke or transient is- After cerebral chemic arrival, prior to questioning, accident); a signed history of cardiac consent ischemia form was (diagnosed required coronary fromdisease artery each or participant. previous All subjects infarction); myocardial were questionedchronicfor a history renal diseaseof(glomerular risk factors, such as:<60 filtration cigarette mL/min) smoking: active,offormer and history (more any aortic than a year without aneurismatic disease. smoking) Anthropometric or nonsmoker; hypertension, measurements were also defined as systolic blood pressure ≥140/90 mmHg or subjects under recorded: height (m), weight (kg), waist circumference (cm) and body mass index (BMI). A antihypertensive treatment; REGICOR dyslipidemia, score [16] was defined as one or determined foralleach of total blood cholesterol individual to evaluate>200 mg/dL, primary low- prevention, density lipoprotein discarding those(LDL) cholesterol subjects who had >100 mg/dL already or triglycerides presented >150 cardiovascular a previous mg/dL or subjects event. under treatmentlevels Cholesterol for dyslipidemia; and blood pressurediabetes, defined required forasscoring those diagnosed were obtained and/or undermedical through an- tidiabetic records. treatment; The REGICOR history(Girona of cerebrovascular Heart Registry) disease research(previous stroke or group focuses ontransient ischemic is- heart chemic cerebral disease accident); history and associated of cardiac risk factors in orderischemia (diagnosed to improve coronary preventive artery disease strategies. This score or assesses previousthe risk of presenting myocardial a cardiovascular infarction); chronic renal event in the(glomerular disease following 10filtration years through <60 a computer-generated mL/min) and history of any calculation that evaluated aortic aneurismatic age, sex, disease. history of smoking, Anthropometric presence of measurements werediabetes and blood also recorded: pressure, height total cholesterol (m), weight (kg), waistand high-density circumference lipoprotein (cm) and body(HDL) mass levels. in- dexLow (BMI).risks are considered A REGICOR scoreto[16]be was scores <5%, moderate determined for each risk between 5toand individual 9% and evaluate high-risk primary subjects >10%. prevention, discarding those subjects who had already presented a previous cardiovascu- lar event. Cholesterol levels and blood pressure required for scoring were obtained 2.3. Physical through medicalAssessment records. The REGICOR (Girona Heart Registry) research group focuses on ischemiccomplete To the assessment, heart disease and associated a physical exam in risk factors was performed, order to improveevaluating preventivedistal pulses strat- through egies. palpation. This score assessesThethepresence of a pulse aincardiovascular risk of presenting one or both tibial arteries event in the was considered following 10 adequate. years through aAfterward, an ABI was computer-generated performed calculation thatinevaluated a standard manner age, [7]: after sex, history a 5 min of smok- ing,rest, with the presence subjects and of diabetes in a blood supinepressure, position,total systolic blood pressure cholesterol was measured and high-density lipopro-at the level of the posterior and anterior tibial arteries of both lower tein (HDL) levels. Low risks are considered to be scores <5%, moderate risk between 5 andextremities and at the level of the brachial artery 9% and high-risk subjects >10%. of both upper extremities, with a continuous wave Doppler probe To complete the assessment, a physical exam was performed, evaluating distal pulses through palpation. The presence of a pulse in one or both tibial arteries was considered adequate. Afterward, an ABI was performed in a standard manner [7]: after a 5 min rest, with the subjects in a supine position, systolic blood pressure was measured at the level J. Clin. Med. 2021, 10, 4467 of the posterior and anterior tibial arteries of both lower extremities and at the level of the 4 of 11 brachial artery of both upper extremities, with a continuous wave Doppler probe (Flow- soft 7 Angiolab1 Spead Doppler Systeme, Kehl, Germany) and an arterial pressure cuff that was placed just above the malleoli. ABI was calculated through the ratio of systolic (Flowsoft pressure 7 Angiolab1 of the Spead tibial arteries Doppler to the highestSysteme, brachial Kehl, Germany) systolic pressure.and ABIanofarterial pressure both extrem- cuff that was placed just above the malleoli. ABI was calculated through ities was recorded. Those with an ABI < 0.9 in one or both lower extremities were consid- the ratio of ered pathological with an indication of PAD. All ABI > 1.4 were registered. In the case of systolic pressure of the tibial arteries to the highest brachial systolic pressure. ABI both that extremities was recorded. Those with an ABI < 0.9 in one or both lower extremities a patient presented with critical limb ischemia, considered as rest pain or presence of is- were considered chemic lesions,pathological they were sent with to an theindication of PAD. All vascular emergency ABI for room > 1.4 were registered. evaluation. At the endIn the case assessment, of each that a patientthe presented withgiven patient was critical limb ischemia, a signed consideredthe report indicating asresult rest pain or presence of their ABI of ischemic lesions, they were sent to the vascular emergency room for evaluation. At exam, and if the exam was pathological, recommendations of the modifiable risk factors the end of each assessment, the patient was given a signed report indicating the result of were given in order to prevent the progression of PAD. their ABI exam, and if the exam was pathological, recommendations of the modifiable risk For better analysis and interpretation of our results, we reviewed common risk fac- factors were given in order to prevent the progression of PAD. tors among our study participants and those obtained from the official health department For better analysis and interpretation of our results, we reviewed common risk factors database, 2018 Catalan Health Survey “Enquesta Catalunya de Salut 2018” (ESCA) (ages among our study participants and those obtained from the official health department 65–74 years old), and our primary care clinics (65 years old), with previous authorization database, 2018 Catalan Health Survey “Enquesta Catalunya de Salut 2018” (ESCA) (ages from our health department. 65–74 years old), and our primary care clinics (65 years old), with previous authorization from our health department. 2.4. Statistical Analysis Descriptive 2.4. analysis was performed, and prevalence of PAD was obtained with the Statistical Analysis 95% confidence Descriptiveinterval. Dichotomous analysis was performed,variables were analyzed and prevalence of PAD through Pearson’s was obtained chi-95% with the square test or Fisher’s confidence interval.exact test. Logistic Dichotomous regression variables weremodels were analyzed used toPearson’s through obtain independ- chi-square enttest associated risk factors or Fisher’s for PAD exact test. thatregression Logistic were previously modelssignificant were used into theobtain bivariate analy- independent sis.associated Interactionrisk effect was also evaluated among these risk factors. Statistical significance factors for PAD that were previously significant in the bivariate analysis. results were considered Interaction for aevaluated effect was also value of pamong < 0.05. these Statistical analysisStatistical risk factors. was performed through significance results IBM SPSS were Statistics for considered forWindows, a value of version p < 0.05.22.0 (IBM Corp., Statistical Armonk, analysis NY, USA).through IBM was performed SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, NY, USA). 3. Results 3. From ResultsNovember 2017 to December 2018, a total of 2808 subjects were 65 years old From during the November time 2017 toADecember of recruitment. 2018, total of 1174 a total subjects of 2808 were subjects finally were included, 65(59.2%) 695 years old during male the(40.8%) and 479 time of female. recruitment. Total A total of 1174rate participation subjects were finally was 43.1%, included, with higher 695 (59.2%) participation male from and 479 females (40.8%) (46.7%) female. than malesTotal participation (40.9%). rate was A flow chart 43.1%, of initial with higher screening withparticipation main re- from females (46.7%) than males (40.9%). sults separated by sex is shown in Figure 2. A flow chart of initial screening with main results separated by sex is shown in Figure 2. Figure 2. Flowchart screening results. The overall prevalence of PAD was 6.2% (95% CI: 4.8–7.6%), male 7.9% (95% CI: 5.9–9.9%) and female 3.8% (95% CI: 2.1–5.5%), most of them corresponding to the Fontaine I classification (n = 53, 72.6%), 20.5% IIA (n = 15), 5.5% IIB (n = 4) and 1.4% (n = 1). The difference in prevalence between male and female was statistically significant (p = 0.006). Male subjects presented at higher risk for PAD, with an OR of 2.2 (CI: 1.3–3.8). There was a total of 18 ABI > 1.4, of which two of these had contralateral ABIs < 0.9 considered PAD. Of the other 16 ABIs > 1.4 (6 were diabetic subjects, and none had chronic J. Clin. Med. 2021, 10, 4467 5 of 11 renal disease), all subjects except for one had palpable distal pulses and none referred to intermittent claudication. Diabetes male subjects were more likely to have PAD (p = 0.017) and female subjects hypertension (p = 0.026) and waist circumference (p = 0.018). No association was seen with a family history of abdominal aortic aneurysm, probably due to the small number of cases detected. Table 1 compares risk factors presented in PAD and non-PAD divided by gender. Table 1. Relationship between PAD and risk factors divided by gender. Logistic regression model with OR and CI 95% of the potential variables associated with PAD. Male Female Non-PAD PAD Total OR * (95% Non-PAD PAD Total OR (95% pa pa (n = 640) (n = 55) (n = 695) CI: **) (n = 461) (n = 18) (n = 479) CI: **) 237 6 243 320 7 327 Non-smoker 1 <0.001 1 0.02 (37.0%) (10.9%) (35.0%) (69.4%) (38.9%) (68.3%) 299 29 328 96 6 102 2.9 Former smoker 3.8 (1.6–9.40) 0.003 0.065 (46.7%) (52.7%) (47.2%) (20.8%) (33.3%) (21.3%) (0.9–8.7) 104 20 124 7.6 45 5 50 5.1 Active smoker <0.001 0.007 (16.3%) (36.4%) (17.8%) (3.0–19.5) (9.8%) (27.8%) (10.4%) (1.5–16.7) Cardiovascular risk factors n (%) 141 20 161 2.0 43 4 47 2.8 Diabetes 0.017 0.083 (22.0%) (36.4%) (23.2%) (1.1–3.6) (9.3%) (22.2%) (9.8%) (0.9–8.8) 293 26 319 1.1 215 10 225 1.4 Dyslipidemia 0.831 0.459 (45.8%) (47.3%) (45.9%) (0.6–1.8) (46.6%) (55.6%) (47.0%) (0.6–3.7) 340 28 368 0.9 181 12 193 3.1 Hypertension 0.752 0.026 (53.1%) (50.9%) (52.9%) (0.5–1.6) (39.3%) (66.7%) (40.3%) (1.1–8.4) Chronic Renal 37 3 40 0.9 8 0 8 0.920 0 0.9 Disease (5.8%) (5.5%) (5.8%) (0.3–3.2) (1.7%) (0%) (1.7%) 59 9 68 1.9 6 1 7 4.5 Cardiac Ischemia 0.092 0.177 (9.2%) (16.4%) (9.8%) (0.9–4.1) (1.3%) (5.6%) (1.5%) (0.5–39.1) Cerebrovascular 31 3 34 1.1 16 0 16 0.840 0 0.9 Events (4.8%) (5.5%) (4.9%) (0.3–3.8) (3.5%) (0%) (3.3%) Anthropometric measurements mean (SD) Waist Circumference 102.4 103.6 102.5 1.01 95.1 102.4 95.3 1.05 0.410 0.018 (cm) (SD 11.0) (SD 9.4) (SD 10.9) (0.99–1.04) (SD 12.1) (SD 15.9) (SD 12.3) (1.01–1.09) Data are expressed as n (%) or mean (standard deviation); * OR: odds ratio; ** CI: confidence interval; a Wald test’s p-values of logistic regression. A multilogistic regression model was performed from the significant bivariate analysis variables. In our male model, an independent association between PAD and smoking was shown. PAD in male subjects was higher in ex-smokers, with an OR of 3.5 (95% CI: 1.4–8-7) and in active smokers 7.2 (95% CI: 2.8–18.6) in comparison with nonsmokers. An association with diabetes and PAD was also seen in our male participants, with an OR of 1.8 (95% CI: 1.0–3.3) As for our female model, an association was also seen in relation to PAD and smoking, with an OR of 3.1 (95% CI: 1.0–9.6) in ex-smokers and 5.2 (95% CI: 1.6–17.3) in active smokers compared with nonsmokers. PAD was also higher in those female subjects with hypertension, with an OR of 3.3 (95% CI: 1.2–9.0) (Table 2). No significant association was seen between hypertension and PAD in male subjects nor diabetes and PAD in our female subjects. Therefore, no interaction effect was observed among these variables, and no mediation effect was observed with gender. Table 2. Multiple logistic regression analysis of PAD risk. Male Female Variables OR (95% CI) Variables OR (95% CI) Non-smokers 1 Non-smokers 1 Former Smokers 3.5 (1.4–8.7) Former Smokers 3.1 (1.0–9.6) Active Smokers 7.2 (2.8–18.6) Active Smokers 5.2 (1.6–17.3) Diabetes 1.8 (1.0–3.3) High blood pressure 3.3 (1.2–9.0) CI: confidence interval. OR: odds ratio. J. Clin. Med. 2021, 10, 4467 6 of 11 Discarding 157 subjects who had already presented a previous cardiovascular event, 1013 subjects were classified according to their cardiovascular risk at 10 years with the REGICOR scale. In this regard, 51.4% (n = 500) of our population were at low risk of developing a cardiovascular event in the following 10 years, 40.4% (n = 393) were at moderate risk and 8.1% (n = 79) were at a high-risk score. Four subjects were excluded from REGICOR analysis due to missing data. Male subjects presented with higher REGICOR scores (p < 0.001), putting them at a higher risk for developing a cardiovascular event in the following 10 years compared to our female subjects. Table 3 illustrates the REGICOR score in our general population divided by sex and PAD. Table 3. REGICOR results in general population separated by sex and PAD. Non-PAD PAD TOTAL MALE FEMALE TOTAL MALE FEMALE (n = 972) (n = 543) (n = 429) (n = 41) (n = 27) (n = 14) Low risk 51.4% 33.1% 74.6% 48.8% 40.7% 64.3% <5% (500) (180) (320) (20) (11) (9) Moderate 40.4% 54.1% 23.1% 41.5% 44.4% 35.7% risk (393) (294) (99) (17) (12) (5) 5–9% High risk 8.1% 12.7% 2.3% 9.8% 14.8% 0% >10% (79) (69) (10) (4) (4) (0) Pearson’s chi-square analysis; 4 subjects without REGICOR. Characteristics of our 1174 studied men and women are best shown in Table 4. Overall, fewer women were smokers (p < 0.001), and our male subjects had higher percentages of diabetes (p < 0.001), high blood pressure (p < 0.001), chronic renal insufficiency (p = 0.001) and cardiac ischemia (p < 0.001), presenting with more risk factors than our female partici- pants. Regarding the history of aneurysmal disease, 3% (n = 35) had a family history of abdominal aneurismatic disease, with 26 of them being a first-degree family member. Table 4. Means and proportions of selected characteristics in the screened population separated by sex. Total Male Female (n = 1174) (n = 695) (n = 479) Cardiovascular Risk Factors% (N) 48.6% 35.0% 68.3% Non-smokers a (570) (243) (327) 14.8% 71.8% 10.4% Active smoker (174) (124) (50) 36.6% 47.2% 21.3% Former smoker (430) (328) (102) 3.0% 2.3% 4% Relative’s history of AAA (35) * (16) (19) * 74.3% 87.5% 63.2% First degree (26) (14) (12) 14.3% 12.5% 15.8% Second degree (5) (2) (3) 17.7% 23.2% 9.8% Diabetes mellitus a (208) (161) (47) 46.3% 45.9% 47% Dyslipidemia (544) (319) (225) 47.8% 52.9% 40.3% Hypertension a (561) (368) (193) 4.1% 5.8% 1.7% Chronic renal disease a (48) (40) (8) J. Clin. Med. 2021, 10, 4467 7 of 11 Table 4. Cont. Total Male Female (n = 1174) (n = 695) (n = 479) Cardiovascular events % (N) 6.4% 9.8% 1.5% Cardiac ischemia a (75) (68) (7) Cerebrovascular 4.3% 4.9% 3.3% events (50) (34) (16) 3.8% 4.5% 2.9% Intermittent claudication (45) (31) (14) Anthropometric measurements % (N) 99.5 102.4 95.3 Waist circumference (cm) b (SD) (12) (10.9) (12.3) 27.7 27.8 27.6 Mean BMI (kg/m2 ) (SD) (4.3) (3.8) (4.9) Normal weight a 28.3 % 24.2% 34.2% (BMI 18.5–24.9) (332) (168) (164) Overweight 46.3% 51.4% 38.8% (BMI 25–30) (543) (357) (186) 25.5% 24.5% 26.9% Obesity (BMI >30) (299) (170) (129) * 4 of these, unknown degree; a p < 0.001 Pearson’s chi-square; b p < 0.001 Student’s t-test; Percentage (n). Mean and standard deviation. Characteristics of our participants with those obtained from the 2018 Catalan Health Survey “Enquesta Catalunya de Salut 2018” (ESCA) and primary care centers located in our area of treatment of Barcelona Nord were reviewed in order to better assess the representation of our sample participants with our overall area of treatment population, as shown in Table 5. Table 5. Characteristics of our study participants and participants of Catalunya Health Survey 2018 (ESCA) and primary care centers of our region of study separated by sex. Our Study Participants ESCA 2018 Primary Care Centers (65 Years Old) (65–74 Years Old) (65 Years Old) Male Female Total Male Female Total Male Female Total (n = 695) (n = 479) (n = 1 174) (n = 206) (n = 224) (n = 430) (n = 1653) (n = 1994) (n = 3647) Active 17.8% 10.4% 14.8% 18.0% 8.0% 12.8% 20.8% 13.4% 16.8% smoker (15.0–20.7) (7.7–13.2) (12.8–16.9) (12.7–23.2) (4.5–11.6) (4.5–11.6) (18.8–22.7) (11.9–14.9) (15.5–17.9) Diabetes 23.2% 9.8% 17.7% 27.2% 20.1% * 23.5% * 23.1% 12.8% * 17.5% mellitus (20.0–26.3) (7.2–12.5) (15.5–19.9) (21.1–33.3) (14.8–25.3) (19.5–27.5) (21.0–25.1) (11.4–14.3) (16.2–18.7) 45.0% * 47.0% 46.3% 34.5% * 46.0% 40.5% * 39.4% * 41.7% * 40.7% * Dyslipidemia (42.2–49.6) (42.5–51.4) (43.5–49.2) (28.0–41.0) (39.5–52.5) (35.8–45.1) (37.1–41.8) (39.5–43.8) (39.1–42.3) 53.0% 40.3% 47.8% 50.5% 48.2% * 49.3% 53.8% 62.9% * 58.8% * Hypertension (49.2–56.7) (35.9–44.7) (44.9–50.6) (43.7–57.3) (41.7–54.8) (44.6–54.0) (51.4–56.2) (60.8–65.1) (57.2–60.4) Chronic 5.8% 1.7% 4.1% 5.8% 6.3% * 6.1% * 4.1% 2.3% 3.1% renal disease (4.0–7.5) (0.5–2.8) (3.0–5.2) (2.6–9.0) (3.1–9.4) (3.8–8.3) (3.1–5.0) (1.6–2.9) (2.5–3.6) Cardiac 9.8% 1.5% 6.4% 7.3% 2.2% 4.7% 8.1% 1.8% 4.7% * ischemia (7.6–12.0) (0.4–2.5) (5.0–7.8) (3.7–10.8) (0.3–4.2) (2.7–6.6) (6.8–9.4) (1.2–2.4) (3.9–5.4) Cerebrovascular 4.9% 3.3% 4.3% 5.8% 2.7% 4.2% 3.1% 1.4% 2.1% * events (3.3–6.5) (1.7–5.0) (3.1–5.4) (2.6–9.0) (0.6–4.8) (2.3–6.1) (2.3–3.9) (0.9–1.9) (1.7–2.6) Overweight 51.4% 38.8% 46.3% 46.6% 42.0% 44.2% 38.2% * 30.9% * 34.2% * (BMI 25–30) (47.7–55.1) (34.5–43.2) (43.4–49.1) (39.8–53.4) (35.5–48.4) (39.5–48.9) (35.8–40.5) (28.9–33.0) (32.7–35.8) Obesity 24.5% 26.9% 25.5% 27.2% 17.4% * 22.1% 27.7% 29.5% 28.7% * (BMI >30) (21.3–27.7) (23.0–31.0) (23.0–28.0) (21.2–33.3) (12.4–22.4) (18.2–26.0) (25.6–29.7) (27.5–31.5) (27.2–30.2) Values are presented as percentages (95% Confidence Interval); Pearson’s chi-square analysis; * Difference in values among both studies. J. Clin. Med. 2021, 10, 4467 8 of 11 4. Discussion In the present study, the prevalence of PAD in asymptomatic patients was 6.2% at age 65, which is in accordance with previous studies carried out in the Mediterranean area [13,14,17]. Risk factors are commonly known to be associated with other atheroscle- rotic diseases, with predominant factors being those of active smoking and diabetes [14]. This was shown to be similar in our study, with associated risk factors being smoking, history of diabetes, cardiac ischemia and a large waist circumference, smoking being the strongest association. Independent risk factors were also seen in logistic regression analysis in male smokers who had a history of diabetes and in female smokers who had hypertension. Knowing the important association of PAD with high cardiovascular risk groups, nonscreening in these subjects could lead to an underdiagnosis or even underesti- mate the true cardiovascular risk of this disease, outlining the importance of screening in these subgroups. 4.1. Differences According to Geography and Age The worldwide prevalence of PAD is estimated to be 3–12% [18], affecting 27 million people in America and Europe [19]. In Europe, the prevalence of PAD is estimated at around 17.8% (99% CI: 16.8–18.8%) in the ages of 45 and 55, seen in the PANDORA study [10]. In Spain, however, the prevalence of PAD is considerably lower. The ESTIME study [20] estimated an 8.03% prevalence in similar age groups as the PANDORA study [10] in Europe, and studies published in the Catalonia Region of Spain concur with these low results. In this sense, Velescu et al. [14] reported a prevalence as low as 4.5% in Girona, and the Perart/Artper group of Barcelona reported a 7.6% prevalence [17]. Although both results are relatively much lower than estimated in Europe and the USA, the observed difference amongst the two might be due in part to the difference in the studied age group, with the Velescu group including subjects as young as 35 years old. This demonstrates the increase in prevalence with age that has already been described previously and the variability of prevalence with geographic regions due to ethnicity and dietary lifestyle, which tend to be unique to each region of study [21,22]. 4.2. Sex Differences Traditionally PAD is thought to be a male-predominant disease [23], but in recent studies, this has been proven otherwise, with an increase of prevalence in elderly women. About 20–30% of women over 70 years old are affected by PAD [24]. Peripheral arterial disease is frequently underdiagnosed due to atypical symptoms and its late presentation in females, and some studies even suggest a 10 to 12 years delay in appearance. Our prevalence of PAD in women was 3.8% compared to 7.9% in males, perhaps partly, again, due to the age group selection, needing further studies to observe prevalence in older female groups. 4.3. Risk Factors The association of PAD with coronary artery disease is observed in 50% of patients and in 20% of patients with cerebrovascular disease [25,26], becoming therefore an important indicator of the coexistence of other cardiovascular disorders [27]. Up to 40% of subjects with PAD die from coronary artery disease and 10–20% by cerebral artery disease [10]. This risk is not only high in asymptomatic subjects but has a straight relationship among symptomatic individuals and severe PAD measured through ABI [28]. Overall, only less than 40% of subjects with PAD do not have concomitant coronary or cerebrovascular disease. Therefore, the association of PAD with other cardiovascular diseases is one of the main concerns of this disease. In our study, 13.6% of our subjects with PAD had an associated history of ischemic heart disease, and only a small few had a history of ischemic cerebrovascular disease. The strongest predictor of PAD in those 65 years and younger has been associated with diabetes and smoking [3], although our study concurs with this from the male sex J. Clin. Med. 2021, 10, 4467 9 of 11 perspective. This was different in our study for females. After logistic regression analysis, we found an independent risk factor association between women who were smokers and had hypertension ORs of 3.3 (95% CI: 1.2–9.0) and 5.2 (95% CI: 1.6–17.3), showing a stronger association between smoking and hypertension than with diabetes in our female group. Stratification of cardiovascular risk was also attempted through the REGICOR score to identify those who had a higher risk of developing a cardiovascular event in the following 10 years. Altogether, we found higher scores in males (p < 0.001) with a high-risk score (considered > 10%) in those with PAD at 14.8% versus those with non-PAD at 12.7%. Therefore, screening with ABI in these subjects we believe to be important for the early implementation of secondary cardiovascular prevention. 4.4. Limitations It should be noted that this study is part of a larger pilot screening program evaluating abdominal aorta aneurysms [8], thus explaining the chosen method of selection. Nonethe- less, in order to minimize any selection bias that could affect our results, we reviewed our study population with the 2018 Catalan Health Survey “Enquesta Catalunya de Salut 2018” (ESCA) [29], focusing on the population age group, 65–74 years of age, and to the data obtained from our primary care centers in 2018, focusing on 65 years of age. We looked into various risk factors among our participants and those of ESCA and our primary care centers shown previously. In general, our participants are similar, although some differences are to be expected due to the wider age group of the survey and different methods of obtaining participant data. All this could lead to some variations seen in our sample participants. Due to limitations in our resources, we were forced to focus on one specific age group in our study. Additionally, our participation rate was 43.1%, which is consistent with the participation rate of other screening programs performed in our region that have a wider broadcasting and media diffusion such as colon and breast cancer screening in Barcelona, which achieved participation rates of 43.6% and 54.7%, respectively [30]. Overall, we believe this is a correct representation of our population, although these limitations should be noted. 5. Conclusions In summary, the overall prevalence of PAD in North Barcelona at 65 years old is still significantly low compared to other regions of Europe [10], and male subjects were still predominantly affected by this disease than females at this age. Our results concur with the literature on this topic for our region [14,17] and outline the strong association between male smokers with diabetes and female smokers with hypertension, stressing the importance of our focus on these subgroups and perhaps emphasizing the need for ABI screening programs, as well as implementing secondary prevention if PAD is confirmed in these specific group of subjects. Additional follow-up studies would be interesting to further evaluate our initial results and differences in sex, as well as prevalence in older populations. Author Contributions: Conceptualization, S.B.-M., G.G.-M. and J.F.; methodology, S.B.-M., G.G.-M. and J.F.; software, S.B.-M., T.P. and R.G.; formal analysis, T.P.; investigation, G.G.-M., S.B.-M., T.P. and R.G.; resources, S.B.-M.; data curation, G.G.-M., D.G.-S., C.T.-D., X.T.-S. and C.M.; writing— original draft preparation, G.G.-M. and S.B.-M.; writing—review and editing, G.G.-M., S.B.-M., T.P., R.G., and D.G.-S.; supervision, S.B.-M., T.P. and R.G.; project administration, S.B.-M., J.F. and T.P.; funding acquisition, S.B.-M. and J.F. All authors have read and agreed to the published version of the manuscript. Funding: This work was logistically supported by the PERIS 2016–2020 medical research grant from Generalitat de Catalunya (Spain). Expedient Number SLT002/16/00441. Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Vall d’Hebron University Hospital (PR(AG)221/2017). J. Clin. Med. 2021, 10, 4467 10 of 11 Informed Consent Statement: Informed consent was obtained of all subjects involved in the study. Data Availability Statement: Not applicable. Acknowledgments: A special thanks to Manuel Quintana Luque (Statistic Department of Hospital Vall d’ Hebron), Judit Solà Roca (Clinical Epidemiology and Public Health Department of Hospital de la Santa Creu i Sant Pau) as well as Darío Gómez and Olga Solà for their help and support of this study. Conflicts of Interest: The authors declare no conflict of interest. Abbreviations PAD peripheral arterial disease ABI ankle–brachial index OR odds ratio CI confidence interval AAA abdominal aortic aneurysm BMI body mass index (kg/m2 ) SD standard deviation References 1. Aronow, W.S. Peripheral arterial disease of the lower extremities. Arch. Med. Sci. 2012, 8, 375–388. [CrossRef] 2. Fowkes, F.G.; Aboyans, V.; Fowkes, F.J.; McDermott, M.M.; Sampson, U.K.; Criqui, M.H. 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