Using ankle-brachial index to detect peripheral arterial disease: Prevalence and associated risk factors in a random population sample

Nutrition, Metabolism & Cardiovascular Diseases (2007) 17, 41e49

www.elsevier.com/locate/nmcd

Using ankle-brachial index to detect peripheral arterial disease: Prevalence and associated risk factors in a random population sample ´n b, Julio Escribano c, Julio A. Carbayo a,*, Juan A. Diviso ´pez de Coca d, Luis M. Artigao b, ´pez-Abril b, Enrique Lo Juan Lo ´ b, Esperanza Martı´nez e, Carlos Sanchis b, Javier Masso ´n b, on behalf of the Grupo de Enfermedades Lucinio Carrio Vasculares de Albacete (GEVA) a

Medical Corps, 14th Fighter Wing Air Base, Albacete, Spain, and School of Medicine, University of Miguel Herna´ndez, San Juan, Alicante, Spain b Community Medicine, Primary Health Care Centre, Albacete, Spain c School of Medicine, University of Castilla-La Mancha, Albacete, Spain d Internal Medicine, Primary Health Care Centre, Albacete, Spain e Biotechnology Group, Institute for Regional Development, University of Castilla-La Mancha, Albacete, Spain Received 29 July 2004; received in revised form 7 March 2005; accepted 5 August 2005

KEYWORDS Peripheral arterial disease; Ankle-brachial index; Risk factors; Arteriosclerosis; Epidemiology

Abstract Background and aim: The ankle-brachial index (ABI) is being used increasingly to diagnose peripheral arterial disease (PAD) that predicts cardiovascular morbidity and mortality. The aim of this study is to determine the prevalence of PAD and associated risk factors in a Spanish random population sample of age 40. Methods and results: PAD is defined as an ABI < 0.9 in either leg. 784 participants of age 40 were randomly selected in a Spanish province. 55.4% of them were female. The prevalence of PAD in this sample was 10.5% (95% confidence interval (CI) 8.4e 12.8); 9.7% in females and 11.4% in males. In logistic regression analyses, adjusted for age and gender, smoking per 10 pack-years (odds ratio (OR) 1.40, 95% CI 1.23e 1.58), hypertension (OR 1.85, 95% CI 1.05e3.28), hypercholesterolemia (OR 1.76, 95% CI 1.04e2.98), and diabetes (OR 1.80, 95% CI 1.04e3.11) were positively associated with prevalent PAD. More than 91% of persons with PAD had one or more cardiovascular disease risk factors.

* Corresponding author. c/ Tesifonte Gallego, 11-8  A, CP 02002 Albacete, Spain. Tel.: þ34 967 520153; fax: þ34 967 522953. E-mail address: [email protected] (J.A. Carbayo). 0939-4753/$ - see front matter ª 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.numecd.2005.08.009

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J.A. Carbayo et al. Conclusions: We conclude that in our study hypertension, hypercholesterolemia, diabetes mellitus and smoking are associated with PAD. The majority of individuals with PAD had at least one important cardiovascular risk factor advanced enough to be considered eligible for an aggressive treatment. ª 2005 Elsevier B.V. All rights reserved.

Introduction Cardiovascular disease, of which coronary heart disease (CHD) is the most frequent, is the principal cause of death in adults in most European countries [1]. The forecast is that by the year 2020, it will be the principal cause of morbidity and mortality in all of these countries combined [2]. The traditional risk factors relate to the extent and severity of the atherosclerotic lesions. As such, subclinical detection of this atherosclerosis burden is of considerable applicability in seeking to improve the prediction of CHD risk [3]. Peripheral arterial disease (PAD) is considered as high risk for developing CHD. Individuals having the disease are treated in the same manner as for secondary prevention [4,5] in addition to the associated mortality produced by CHD [6], morbidity and mortality produced by cardiovascular diseases [7] and all-cause mortality [3,8,9]. The detection of PAD is of special interest since atherosclerosis is considered a generalized disease, and diagnosis of PAD frequently indicates atherosclerosis in other vessel beds [3] as well. The presence of PAD can be determined relatively easily using the ankle-brachial blood pressure index (ABI). This non-invasive test has shown that a value of <0.90 can be considered as evidence of PAD [3]. Similar studies have been conducted in other countries but, to our knowledge, there is none for our geographic area (South-East Spain). Therefore, the objectives of the present study have been to describe the prevalence of ABI in a random population sample and to evaluate relationships with other associated atherosclerosis risk factors in individuals older than 40.

Methods Participants The primary population sample was drawn from the general population >18 years of age in the province of Albacete (population of 218,462 inhabitants; 53.8% female) in the Autonomous Community of Castilla La-Mancha (South-East Spain). For the study sample to be representative, subjects were randomly recruited from the population

census of 1991, which included 22 towns in the Province. The description of the population has been presented elsewhere [10]. Briefly, the study sample was random, stratified and two-staged with the stages proportional to the size of the population from which the sample was drawn. The study was approved by, and received the active cooperation of, the local health authorities (Delegacio ´n Provincial de Sanidad de la Junta de Comunidades de Castilla-La Mancha). The methodology was standardized particularly with respect to the use of the portable Doppler equipment used for lower limb blood pressure measurements. All data were recorded on sheets prepared by the GEVA group. On the day following the physical examination, before any food ingestion, a venous blood sample was taken and delivered to the central laboratory for analysis. The ABI and other risk factor values were established in the overall population sample and subsequent associations between variables were assessed in those aged 40 using bivariate and multivariate analysis.

Measurement techniques The ABI values were measured by physicians trained at the Section of Vascular Surgery of the Albacete General Hospital. With the patient supine and the feet uncovered, lower extremity pressure was measured with a portable Doppler model ES1000 SPM, applying the Doppler probe at an angle of approximately 60  in the direction of blood flow on the anterior or the posterior tibialis artery. The cuff of the apparatus was inflated rapidly in each ankle (right posterior tibialis, right dorsal pedialis, left posterior tibialis, left dorsal pedialis) about 30 mmHg above the systolic pressure followed by a slow descent of about 2 mmHg per second until the first sound of the systolic pressure became audible. Blood pressure was measured on both arms and the consensus technique recommendations of the different scientific societies [11] were strictly adhered to. The measurements were done twice within a period of 3e5 min and the lower value was used in subsequent calculations of the prevalence.

Peripheral arterial disease and risk factors The ankle-brachial index was calculated separately for each foot dividing the higher of the two systolic ankle pressures (pedialis or posterior tibialis) by the higher of the two systolic pressures of the arm [12]. Peripheral arterial disease was assumed if the calculated ABI was <0.90 in either foot [3].

Other variables Laboratory analyses such as glucose, total cholesterol, HDL cholesterol (HDLc), triglycerides and fibrinogen were measured on blood samples obtained following an overnight fast of 12 h on the day following the physical examination and blood pressure measurements. Glucose, total cholesterol and triglycerides were measured using enzymatic techniques. HDLc was obtained by precipitation with phosphotungstic acid and magnesium chloride. Fibrinogen was measured by the method of Clauss Ortho QFA (Boehringer Mannheim, Mannheim, Germany). Data were collated on forms designed to record the family history of premature (55 years of age) CHD in first degree family members, the personal history of CHD (angina pectoris of whatever type or myocardial infarction), cerebrovascular disorders (CVD) such as stroke or transient ischemic attack (TIA) or PAD. This last condition was measured using the clinical classification of La Fontaine but excluding stage I because of its imprecise definition. Hypertension was assumed when measurements were 140 systolic and/or 90 mmHg diastolic [13] or the individual was taking antihypertensive drugs. Smoking habit was defined as the consumption of at least 1 cigarette daily at the time of the physical examination. The number of cigarettes consumed per day was noted and expressed as the number of pack-years (number of years that an individual had smoked multiplied by the mean number of packets of cigarettes consumed per day per year). The presence of diabetes was defined as a fasting glucose concentration of 7 mmol/L measured on two occasions or if the subject was receiving oral hypoglycemic drugs or insulin [14]. Hypercholesterolemia was defined as the concentration of total cholesterol 6.5 mmol/L [15]. Body mass index (BMI) was calculated as the individual’s weight in kilograms divided by the height in meters squared (kg/m2). From this, three categories of body-weight were defined: normal body weight (BMI ¼ 18.5e24.9 kg/m2) overweight (BMI ¼ 25e29.9 kg/m2) and obese (BMI  30) [16]). Hyperfibrinogenemia was defined as fibrinogen concentration >400 mg/dL [17].

43

Data analysis The study was observational, descriptive, analytical and cross-sectional. The ABI, as a quantitative variable, has been expressed as the mean and standard deviation (SD), and stratified with respect to gender and age decade. In testing the relationships between ABI and the variables of interest, the subjects 40 years of age were analyzed separately. In this group of individuals, the evaluations of the prevalence of cardiovascular disease and all the risk factors measured were performed by dividing the ABI values into two categories (<0.9 and 0.9). Comparison of means was performed with the Student t-test for independent groups or the ManneWhitney U-test if the conditions of normality of distribution (applying KolmogoroveSmirnoff or ShapiroeWilks tests) were not fulfilled. For qualitative variables the Chi-squared test was used. Crude odds ratios (ORs), adjusted ORs and their 95% confidence intervals (CIs) were estimated with logistic regression models. All values of p < 0.05 were considered significant. The analyses of data were performed using the SPSS software (SPSS for Windows, version 10.0; 1999, SPSS Inc, Chicago, IL).

Results The number of participants in the primary sample was 1322 (711 females) of whom 3 were subsequently excluded because of technical difficulties in obtaining ankle blood pressure measurements. Fig. 1 summarizes the ABI measurements expressed as mean and SD, with respect to gender and age decade. The mean values of ABI decrease with age in both males and females and stabilize in females over 60. Levels are higher in males except for those individuals beyond age 70. After this age, this gender relationship is inverted. In all cases the mean values were above the 1.0 cut-off considered as normal [18]. We excluded 8 individuals who had ABI > 1.5, values usually related to non-compressible vessels in the legs [19]. The final sample considered in this study was for ages 40 and included 784 (434 females; 55.4%). The mean age of these participants was 59.8 years (SD ¼ 11.6) for females and 60.2 years (SD ¼ 11.7) for males. The mean age of the population (60.0 years, SD ¼ 11.6) was therefore similar to that of the Framingham Offspring Study cohort [20]. The overall prevalence of PAD was 10.5% (95% CI 8.4e12.8; 82 individuals) for ABI < 0.9. Fig. 2 presents this prevalence for different age and

44

J.A. Carbayo et al. 1.12 1.1

Ankle-brachial index

Females

1.1 (0.12)

Males

1.08 (0.17)

1.08 1.05 (0.19)

1.06 1.04

1.05 (0.09)

1.02

1.01 (0.26) 1.03 (0.10)

1.02 (0.09)

1 0.98

1.02 (0.14) P=0.002

P=0.004

P=0.127

P=0.780

40-49 years

50-59 years

60-69 years

70 and older

F=100 M=75

F=113 M=89

F=119 M=105

F=102 M=81

0.96

Figure 1 Mean values (standard deviation) of the ankleebrachial index in the different age groups, stratified by gender. Comparison between groups was made with the Student t-test. F: Females; M: Males.

1.63, 95% CI 1.34e1.97), for each 10 pack-years smoked (OR 1.40, 95% CI 1.23e1.58), hypertension (OR 1.85, 95% CI 1.05e3.28), hypercholesterolemia (OR 1.76, 95% CI 1.04e2.98), diabetes (OR 1.80, 95% CI 1.04e3.11) and medical history of any cardiovascular disease (OR 3.12, 95% CI 1.70e5.73). After the multivariable analyses the ORs changed only slightly and only hypercholesterolemia did not, in this case, reach statistical significance although it was close to it (p ¼ 0.07). Hyperfibrinogenemia displays a significant crude OR, but this loses statistic significance if it is adjusted by age and gender, and in the multivariable adjusted OR. These data provided no evidence that BMI was associated with prevalent PAD.

Discussion Mean ABI values were found to be significantly higher in males between the ages of 40 and 59, and

Males Females

30

Prevalence (%)

gender groups. The prevalence almost doubles after age 70 with respect to the 60e70 age range for both genders. Table 1 provides a summary of the variables known to be related to atherosclerosis for both genders. Personal history of cardiovascular disease, smoking habit and number of pack-years of cigarettes was significantly higher in males. On the other hand, females presented greater obesity and arterial hypertension. In general, males were at higher risk for the development of coronary heart disease (higher triglycerides, lower HDLc, higher non-HDL cholesterol) while females had a high level of fibrinogen in general. Table 2 summarizes the relationships between the two levels of ABI and the different risk factors measured for both genders. In both males and females an ABI < 0.9 was associated with older individuals. With the exception of hyperfibrinogenemia (larger percent for both genders with ABI < 0.9), the other variables differ. Females with ABI < 0.9 have higher levels of arterial hypertension, hypercholesterolemia and, at least for 92.9% of them, one cardiovascular risk factor is present. Males with ABI < 0.9 have a medical history with the largest occurrence of coronary heart disease, peripheral arterial disease and cardiovascular disease. Diabetes is more frequent among them, and the proportion of smokers and the number of packyears are also the largest. However, body mass index (BMI) is smaller than in individuals outside this group. The adjusted and non-adjusted ORs are presented in Table 3. In the analysis, adjusted according to age and gender, the classical factors for the development of cardiovascular disease were associated with PAD for each 10 years elapsed (OR

24.7

25 20

15.7

15

10.6

10 5

4

5

5.6

11.4 7.6

0 40-49

50-59

60-69

70 or more

Age groups (years)

Figure 2 Prevalence of peripheral arterial disease by sex and age in adults aged 40 or more years in a randomised population in the province of Albacete (Spain).

Peripheral arterial disease and risk factors Table 1

45

Risk factors in the subpopulation 40 years of age stratified with respect to gender

Risk factors Age; years (SD) Family antecedents of CHD; n (%) Personal history of CHD; n (%) Personal history of CVD; n (%) Personal history of PAD; n (%) Personal history of CD; n (%) Diabetes; n (%) Arterial hypertension; n (%) Current smoker; n (%) Pack-years; (SD); (n ¼ 150 smokers) BMI; kg/m2 (SD) Obesity; n (%) Normal weight Overweight Obesity Glucose; mmol/L (SD) Cholesterol; mmol/L (SD) Hypercholesterolemia; n (%) Triglycerides; mmol/L (SD) HDLc; mmol/L (SD) HDLc  1.035 mmol/L; n (%) Non-HDLc; mmol/L (SD)a Fibrinogen; mg/dL (SD) Hyperfibrinogenemia; n (%)

Females (n ¼ 434) 59.8 40 14 11 3 25 68 278 18 13.5 29.7 77 164 193 5.90 5.44 84 1.18 1.28 333 4.17 360.6 117

(11.6) (9.2) (3.2) (2.5) (0.7) (5.8) (15.7) (64.1) (4.1) (18.3) (n ¼ 18) (5.1) (17.7) (37.8) (44.5) (2.06) (0.94) (19.4) (0.75) (0.31) (76.7) (0.94) (65.1) (27.0)

Males (n ¼ 350) 60.2 28 25 19 15 50 50 197 132 32.0 27.7 87 170 93 5.87 5.45 63 1.39 1.11 192 4.34 348.7 82

p

(11.7) (8.0) (7.1) (5.4) (4.3) (14.3) (14.3) (56.3) (37.7) (2.9) (n ¼ 132) (4.0)

0.637 0.547 0.012 0.036 0.001 <0.001 0.590 0.027 <0.001 <0.001* <0.001

(24.9) (48.6) (26.6) (1.71) (0.97) (18.0) (0.82) (0.28) (54.9) (0.99) (74.7) (23.4)

<0.001 0.836 0.907 0.629 <0.001 <0.001 <0.001 0.012 0.017 0.259

The value of p is calculated by applying the Student t-test for quantitative variables and the Chi-squared test for qualitative variables. *Calculated with the ManneWhitney U-test. SD, standard deviation; CHD, coronary heart disease; CVD, cerebrovascular disorders (stroke or transient ischemic attack); PAD, peripheral arterial disease; CD, cardiovascular disease (CHD, CVD, and/or PAD). HDLc, high-density lipoprotein cholesterol. a Total cholesterol minus HDL cholesterol.

this trend was reversed in those above age 70 but still remaining within the normal cut-off level. An accumulation of factors in relation to PAD could explain this change in males, including episodes of CVD in the personal medical history, the greater number of smokers and the greater quantity of tobacco consumed when comparing with females who smoked (4.1%). We calculated the prevalence of PAD, as determined by ABI, as between 10% and 11%. This value is very similar to that observed by Weitz et al. [21] and Buitron-Granados et al. [22], with 10% of individuals with an ABI < 0.9, but lower than that found by Newman et al. [18] in subjects 65 years of age (12.4%). However, the value was larger than the 3e4% obtained in the Framingham study [20] with individuals older than 40 and the one obtained by Selvin et al. [23] in a US representative sample, also for individuals older than 40 (4.3%) with the same ABI cut-off point as our study. It is possible that their value underestimates the true prevalence in the U.S. population, as indicated by the authors, because some values were not directly measured but supplied by each person. In our case,

we verified the medical history of each person. In the logistic regression analysis adjusted by age and gender, the association of the main risk factors with PAD differs only very slightly from the data presented in the two studies cited above. When other variables are taken into account in the adjustment, the following lose statistic significance: hypertension in Selvin et al. [23], diabetes and hypercholesterolemia in Murabito et al. [20] and hypercholesterolemia in ours. In the study of Halmayer et al. [24], considering individuals with symptomatic PAD angiographically evaluated, no association with lipid profile or with fibrinogen was found. Concerning this last parameter, our study detected a higher fibrinogen levels in males (37.5%; p ¼ 0.026) and in females (42.9%; p ¼ 0.015) with an ABI < 0.9, along with a significant crude OR, which decreased with the adjustment until losing statistical significance, in agreement with the results of Halmayer et al. [24]. It is well known, and our study confirms it, that females have higher fibrinogen values than males [25]. The relationship between smoking habit (represented as the number of pack-years) and

46

J.A. Carbayo et al.

Table 2 Prevalence of cardiovascular disease and risk factors in males and females stratified by ankle-brachial index level ABI < 0.9 Males (N ¼ 350) N (%) Age; years (SD) Family antecedents CHD; n (%) Personal antecedents CHD; n (%) Personal antecedents CVD; n (%) Personal antecedents PAD; n (%) Personal antecedents CD; n (%) Diabetes; n (%) Arterial hypertension; n (%) Current smoker; n (%) Pack-years; (SD) (n ¼ 131 smokers) BMI; kg/m2 (SD) Obesity; n (%) Normal weight Over weight Obesity Glucose; mmol/L (SD) Total cholesterol; mmol/L (SD) Hypercholesterolemia; n (%) Triglycerides; mmol/L (SD) HDLc; mmol/L (SD) HDLc  1.035 mmol/L; n (%) Non-HDLc; mmol/L (SD) Fibrinogen; mg/dL (SD) Hyperfibrinogenemia; n (%) Hypertension, hypercholesterolemia, diabetes or current smoking; n (%)a Females (N ¼ 434) N (%) Age; years (SD) Family antecedents CHD; n (%) Personal antecedents CHD; n (%) Personal antecedents CVD; n (%) Personal antecedents PAD; n (%) Personal antecedents CD; n (%) Diabetes; n (%) Arterial hypertension; n (%) Current smoker; n (%) Pack-years; (SD) (n ¼ 18 smokers) BMI; kg/m2 (SD) Obesity; n (%) Normal weight Over weight Obesity Glucose; mmol/L (SD) Total cholesterol; mmol/L (SD) Hypercholesterolemia; n (%) Triglycerides; mmol/L (SD) HDLc; mmol/L (SD) HDLc  1.035 mmol/L; n (%) Non-HDLc; mmol/L (SD) Fibrinogen; mg/dL (SD)

40 68.1 3 10 4 9 19 12 27 21 50.9 26.4

(11.4) (10.9) (7.5) (25.0) (10.0) (22.5) (47.5) (30.0) (67.5) (52.5) (26.8) (n ¼ 21) (3.7)

ABI  0.9 310 59.2 25 15 15 6 31 38 170 111 28.7 27.9

13 19 8 6.01 5.60 8 1.57 1.08 19 4.52 368.9 15 36

(32.5) (47.5) (20.0) (1.95) (0.84) (20) (0.91) (0.28) (47.5) (0.89) (73.1) (37.5) (90.0)

74 151 85 5.85 5.43 55 1.37 1.11 173 4.32 346.1 67 251

42 63.9 5 2 0 1 3 10 37 2 41.5 30.6

(9.7) (11.5) (11.9) (4.8)

392 59.4 35 12 11 2 22 58 241 16 10.0 29.5

7 12 23 5.96 5.58 16 1.21 1.26 34 4.32 374.4

(16.7) (28.6) (54.8) (1.92) (1.05) (38.1) (0.49) (0.24) (81.0) (1.08) (89.7)

(2.4) (7.1) (23.8) (88.1) (4.8) (54.4) (n ¼ 2) (5.7)

70 152 170 5.90 5.43 68 1.17 1.28 299 4.15 359.1

(88.6) (11.4) (8.1) (4.8) (4.8) (1.9) (10.0) (12.3) (54.8) (35.8) (20.2) (n ¼ 110) (4.0)

p

<0.001 0.901 <0.001 0.175 <0.001 <0.001 0.003 0.129 0.04 <0.001* 0.029

(23.9) (48.7) (27.4) (1.67) (0.99) (17.7) (0.80) (0.29) (55.8) (1.00) (74.6) (21.6) (81.0)

0.405 0.637 0.249 0.726 0.184 0.496 0.320 0.188 0.069 0.026 0.162

(90.3) (11.5) (8.9) (3.1) (2.8) (0.5) (5.6) (14.8) (61.5) (4.1) (7.9) (n ¼ 16) (5.0)

0.018 0.526 0.553 0.271 0.164 0.686 0.127 0.001 0.834 0.549* 0.206

(17.9) (38.8) (43.4) (2.07) (0.93) (17.3) (0.77) (0.32) (76.3) (0.93) (61.9)

0.336 0.841 0.306 0.001 0.782 0.718 0.495 0.263 0.287

Peripheral arterial disease and risk factors

47

Table 2 (continued) Hyperfibrinogenemia; n (%) Hypertension, hypercholesterolemia, diabetes or current smoking; n (%)a

ABI < 0.9

ABI  9

p

18 (42.9) 39 (92.9)

99 (25.3) 282 (71.9)

0.015 0.003

The value of p is calculated by applying the Student t-test for quantitative variables and the Chi-squared test for qualitative variables. *Calculated with the ManneWhitney U-test. ABI, ankle-brachial index; SD, standard deviation; CHD, coronary heart disease; CVD, cerebrovascular disorders (stroke or transient ischemic attack); PAD, peripheral arterial disease; CD, cardiovascular disease (whether CHD, CVD and/or PAD); HDLc, high-density lipoprotein cholesterol. a When the whole population (without gender separation) is evaluated, 91.5% (75 cases) of the individuals with ABI < 0.9 had at least one cardiovascular risk factor, to be compared with 75.9% (n ¼ 533; p ¼ 0.001) among those with ABI > or ¼ 0.9.

hypertension and low ABI is in general agreement with the published studies [20,23]. The relationship with diabetes as an independent risk factor has been described in some studies [23] but not in others [20], and the latter authors suggest that diabetes did not appear in the multivariate analysis model because the exclusion criteria of subjects with ABI > 1.5 would exclude those who have a higher probability of having diabetes. In

our study this exclusion represented only eight individuals. The clinical and analytical differences between males and females are well known (larger BMI in females and also larger number of hypertensive individuals with less smokers and larger concentration in HDLc levels), in agreement with data from a recent study in Spain, although in that study the sample was not purely random but for ages

Table 3 Odds ratios (95% CIs) for PAD and selected risk factors associated with peripheral arterial disease as defined by ABI < 0.9 Risk factor

Crude OR (95% CI) p

Age- and genderp adjusted OR (95% CI)

Age (per 10 years) History of CHD No Yes History of any CD No Yes Pack-years of smoking (per 10 pack-years) BMI (kg/m2) <25 25e29 30 Hypertension No Yes Hypercholesterolemia No Yes Diabetes No Yes Hyperfibrinogenemia No Yes

1.66 (1.34e2.04)

<0.001 1.63 (1.34e1.97)

<0.001 1.52 (1.20e1.99)

0.001

1 4.29 (2.08e8.83)

1 <0.001 2.75 (1.29e5.86)

1 0.009 3.11 (1.37e7.07)

0.007

1 4.49 (2.56e7.89) 1.29 (1.63e1.44)

1 <0.001 3.12 (1.70e5.73) <0.001 1.40 (1.23e1.58)

1 <0.001 3.25 (1.68e6.32) <0.001 1.48 (1.22e1.60)

<0.001 <0.001

1 0.74 (0.41e1.34) 0.88 (0.48e1.59)

0.32 0.66

1 2.52 (1.46e4.34) 1 1.95 (1.17e3.26)

0.01

1 0.73 (0.40e1.34) 0.84 (0.45e1.56)

Fully adjusted p modela OR (95% CI)

1 0.67 (0.35e1.29) 0.75 (0.38e1.47)

0.23 0.40

1 0.001 1.85 (1.05e3.28)

1 0.035 1.95 (1.06e3.59)

0.03

1 1.76 (1.04e2.98)

1 0.034 1.65 (0.95e2.85)

0.07

1 2.32 (1.36e3.50)

1 0.002 1.80 (1.04e3.11)

1 0.037 1.83 (1.03e3.27)

0.04

1 2.18 (1.35e3.50)

1 0.001 1.60 (0.97e2.64)

1 0.067 1.38 (0.82e2.32)

0.23

0.30 0.58

CI, confidence interval; PAD, peripheral arterial disease; ABI, ankle-brachial index; OR, odds ratio; CHD, coronary heart disease; CD, cardiovascular disease (whether CHD, cerebrovascular disorders (stroke or transient ischemic attack) and/or PAD); BMI, body mass index. a Adjusted for age, gender, smoking, BMI, hypertension, hypercholesterolemia, diabetes and hyperfibrinogenemia.

48 between 60 and 79 [26]. This has been highlighted separately as shown in Table 2, with the prevalence of cardiovascular disease and risk factors stratified by ankle-brachial index level. The observed differences indicate that males with PAD compared with those who do not have it are older, have a clinical history where diabetes and CD are more frequent, the proportion of smokers greater and the number of cigarettes smoked higher. However, there are no differences in the analytical parameters. Females with PAD in general are older than those who do not have it and more hypertensive and hypercholesterolemic, with higher fibrinogen levels. Analyzing according to age and gender shows that clinical history with CD, smoking habit, hypertension, hypercholesterolemia and diabetes are all variables that have remained independently associated with PAD, as shown in Table 3. That is to say, with the traditional risk factors, our findings were in agreement with studies which included a non-institutionalized population [20,23]. In addition, 90% of males with PAD had at least one of the four traditional risk factors cited above. In females, this proportion reached 92.9% (91.5% including total population). This means a greater intensive treatment for these risk factors, in agreement with the available evidence [4,27]. In conclusion, we have described the prevalence of PAD and risk factors found in a random population of a province in southeast Spain. In this region, the PAD increases especially in ages 70 and 91.5% of all individuals with an ABI < 0.9 show at least one classical cardiovascular risk factor, which requires close and adequate attention and an aggressive risk factor management. Arterial hypertension and diabetes mellitus increase the odds of PAD by a factor of 2 while a personal history of cardiovascular disease increases this 3.25, smoking by 1.5 for every 10 pack-years and age by 1.5 for every 10 years. Longitudinal studies are needed to value the prediction of PAD in cardiovascular morbidity/mortality, and all-cause mortality in the Spanish population.

J.A. Carbayo et al.

[2] [3]

[4]

[5]

[6]

[7]

[8] [9]

[10]

[11]

[12]

[13]

[14]

[15]

Acknowledgements We thank Dr. Pedro Mata, Lipid Clinic, Fundacio ´n Jime ´nez Dı´az, Spain for his inestimable help and advice when preparing the manuscript.

[16]

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