Preventive Medicine 63 (2014) 48–51
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Regular use of aspirin for cardiovascular disease prevention in Italy Alessandra Lugo a,b, Rosario Asciutto c, Cristina Bosetti a, Fabio Parazzini b,d, Carlo La Vecchia b, Silvano Gallus a,⁎ a
Department of Epidemiology, IRCCS — Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy Department of Sciences for the Health Promotion and Mother and Child Care “G. D'Alessandro”, Hygiene Section, University of Palermo, Palermo, Italy d Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy b c
a r t i c l e
i n f o
Available online 7 March 2014 Keywords: Aspirin Cardiovascular risk Diabetes Hypertension Hypercholesterolemia Prevention Italy
a b s t r a c t Objective. Only a few European studies focused on aspirin use in the general population. We provide updated information on the prevalence and determinants of regular aspirin use for the prevention of cardiovascular disease (CVD) in the Italian adult population. Method. We used data from a survey conducted in Italy in 2013, on a sample of 3000 individuals, representative of the general Italian population aged ≥15 years. Results. Overall, 10.9% of Italians reported a regular use of aspirin, 11.2% of men and 10.5% of women. Aspirin use signiﬁcantly increased with age. The highest prevalence of aspirin use was observed among the elderly (30.3%), ex-smokers (22.6%), and in individuals with a diagnosis of diabetes (52.0%), hypertension (42.6%) or hypercholesterolemia (38.6%). After adjustment for several covariates, no signiﬁcant heterogeneity in aspirin use was observed according to education, body mass index, and physical activity. Only 1.2% of low CVD risk individuals regularly used aspirin versus 48.3% of individuals with high CVD risk. Conclusion. About 3.4 million high CVD risk Italians do not regularly use aspirin for primary or secondary prevention. Thus, more widespread preventive strategy is recommended for this population, once individual beneﬁts of regular aspirin use exceed harms. © 2014 Elsevier Inc. All rights reserved.
Introduction Aspirin has a beneﬁcial effect in the prevention of cardiovascular disease (CVD) (Cleland, 2013; Hennekens and Dalen, 2013) and probably of a number of common cancers (Bosetti et al., 2012; Cleland, 2013; Cuzick et al., 2009). However, the use of aspirin may cause gastrointestinal bleeding (Cleland, 2013; Hennekens and Dalen, 2013; U.S. Preventive Services Task Force, 2009). Thus, aspirin use as primary prevention for CVD should be recommended to individuals whose absolute beneﬁts outweigh risks, i.e., individuals with high risk of CVD (Hennekens and Dalen, 2013; U.S. Preventive Services Task Force, 2009). Only a few studies provided information on the prevalence of aspirin or other non-steroidal anti-inﬂammatory drug (NSAID) use in Europe (Fosbol et al., 2008; Rodondi et al., 2008) and, to our knowledge, only one survey provided information on NSAID use in the general Italian population (Motola et al., 2004). That survey showed that in 2002
⁎ Corresponding author at: Department of Epidemiology, IRCCS — Istituto di Ricerche Farmacologiche “Mario Negri”, Via Giuseppe La Masa 19, 20156 Milan, Italy. Fax: +39 0233200231. E-mail address: [email protected]
http://dx.doi.org/10.1016/j.ypmed.2014.03.005 0091-7435/© 2014 Elsevier Inc. All rights reserved.
NSAIDs were regularly used (i.e., daily or frequently for more than 6 months) by 4.2% of Italian adults. Another Italian study on 540,984 community outpatients of 400 Italian general practitioners (GPs) reported that in 2005 8.3% of individuals had at least one aspirin prescription (Filippi et al., 2011). Other two Italian studies investigated regular use of aspirin in selected population subgroups, such as cardiologists (Temporelli et al., 2013) and elderly adults (Pilotto et al., 2003). In Italy, decreased trends in mortality for CVD (Araujo et al., 2013) and aspirin-related cancers (Arfe et al., 2011) have been observed over the last decade. We provide here updated information on the prevalence and determinants of aspirin use in the general Italian population, given the limited data on the issue. Methods We used data from a survey conducted in 2013 on a sample of 3000 subjects (1442 men and 1558 women), representative of the general Italian population aged ≥15 years (i.e., 51.1 million inhabitants) in terms of sex, age, geographic area, and socio-economic characteristics. Participants were selected through a representative multistage sampling from 116 municipalities in the 20 Italian regions. In the municipalities considered, individuals were randomly sampled from electoral rolls, within strata
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deﬁned by sex and age group, in order to be representative of the demographic structure of the population. Unavailable participants were replaced by their neighbors (living in the same ﬂoor/building/street) with the same sex and age group. Statistical weights were used to assure representativeness of the Italian population aged 15 years or over. Individuals were interviewed through a structured questionnaire in the context of a computer-assisted personal in-house interview (CAPI). Besides general information on demographic, socio-economic and other selected characteristics, participants were asked about their regular use of aspirin or other NSAIDs for the prevention of CVD or cancer. Moreover, participants were asked to report previous diagnosis of diabetes, hypertension, and hypercholesterolemia (i.e., cholesterol N 200 mg/dl). We computed body mass index (BMI) as the ratio between weight (kg) and height (m2); BMI was then categorized as: underweight (BMI b 18.5 kg/m2), normal weight (18.5 ≤ BMI ≤ 24.9 kg/m2), overweight (25.0 ≤ BMI ≤ 29.9 kg/m2) and obese (BMI ≥ 30.0 kg/m2). On the basis of validated CVD risk charts and guidelines (Perk et al., 2012; U.S. Preventive Services Task Force, 2009), we created an ad hoc score to categorize individuals according to their CVD risk, on the basis of 6 major CVD risk factors (i.e., age, diabetes, smoking, obesity, hypertension, and hypercholesterolemia). Odds ratios (OR) and corresponding 95% conﬁdence intervals (CI) for aspirin use versus non use were estimated by unconditional multiple logistic regression models after adjustment for sex, age (12 categories: 15–24, 25–34, …, 80–84, ≥ 85 years), level of education, geographic area, smoking status, BMI, physical activity, and history of diabetes, hypertension, and hypercholesterolemia.
Results Overall, 10.9% of Italians aged ≥15 years reported a regular use of aspirin or other NSAIDs. Users were more frequently men (11.2%) than women (10.5%; Table 1). Aspirin use increased with age (1.0% in individuals aged 15–44 years, 10.3% in 45–64, and 30.3% in ≥65 years). The highest prevalence of aspirin use was observed in less educated individuals (20.2%), central Italy (16.2%), ex-smokers (22.6%), obese adults (16.9%), individuals reporting a low physical activity (13.6%), and individuals with a previous diagnosis of diabetes (52.0%), hypertension (42.6%) or hypercholesterolemia (38.6%). In multivariate analysis, ORs were signiﬁcantly increased for individuals aged 45–64 years (OR: 3.59) and ≥65 years (OR: 5.88) compared to those aged 15–44 years (p for trend b0.001), for central compared to northern Italy (OR: 1.78), for ex-smokers compared to never smokers (OR: 1.59), and for individuals with a history of diabetes (OR: 2.35), hypertension (OR: 6.45) and hypercholesterolemia (OR: 3.06) compared to those with no corresponding disease. No signiﬁcant heterogeneity in aspirin use was observed according to level of education and BMI, and a measure of physical activity. In a sensitivity analyses, excluding mutual adjustment for various comorbidities, the OR of aspirin use was 4.00 (95% CI: 2.65–6.03) for individuals with a history of diabetes, 9.47 (95% CI: 6.88–13.04) for hypertension, and 5.35 (95% CI: 4.02–7.12) for hypercholesterolemia.
Table 1 Percent prevalence (%) of regular use of aspirin or other non-steroidal anti-inﬂammatory drugs for the prevention for cardiovascular diseases and corresponding odds ratios (OR) and 95% conﬁdence intervals (CI), overall and in strata of selected characteristics. Italy, 2013.
Total Sex Men Women Age group (years) 15–44 45–64 ≥65 p for trend Education No/elementary/middle school High school University or higher p for trend Geographic area Northern Italy Central Italy Southern Italy and islands Smoking status Never smoker Ex-smoker Current smoker Body mass index (BMI) Underweight/normal weight Overweight Obese p for trend Physical activity (minutes of walk/day) b30 30–60 N60 p for trend Diabetes No Yes Hypertension No Yes Hypercholesterolemia No Yes
OR (95% CI) for aspirin use vs. non usea
% of aspirin use (95% CI)
11.2 (9.6–12.8) 10.5 (9.0–12.0)
1b 0.86 (0.63–1.18)
1343 948 709
1.0 (0.5–1.5) 10.3 (8.3–12.2) 30.3 (26.9–33.7)
1b 3.59 (1.92–6.70) 5.88 (3.09–11.2) b0.001
1193 1362 445
20.2 (17.9–22.5) 5.1 (4.0–6.3) 3.3 (1.7–5.0)
1b 0.78 (0.54–1.12) 0.72 (0.38–1.35) 0.144
1379 596 1025
9.7 (8.1–11.2) 16.2 (13.3–19.2) 9.3 (7.5–11.1)
1b 1.78 (1.22–2.58) 0.92 (0.65–1.31)
1991 392 616
9.6 (8.3–10.9) 22.6 (18.4–26.7) 7.5 (5.4–9.6)
1b 1.59 (1.08–2.33) 0.99 (0.65–1.52)
1727 878 395
7.6 (6.4–8.9) 14.5 (12.2–16.9) 16.9 (13.2–20.6)
1b 0.98 (0.70–1.36) 1.03 (0.68–1.57) 0.921
1229 1204 567
13.6 (11.6–15.5) 9.0 (7.4–10.6) 8.9 (6.6–11.2)
1b 0.80 (0.57–1.12) 0.89 (0.59–1.36) 0.402
8.9 (7.9–10.0) 52.0 (43.5–60.4)
1b 2.35 (1.50–3.68)
3.0 (2.3–3.6) 42.6 (38.6–45.6)
1b 6.45 (4.59–9.04)
4.4 (3.6–5.2) 38.6 (34.6–42.6)
1b 3.06 (2.24–4.19)
a Estimated using unconditional multiple logistic regression models after adjustment for sex, age, level of education, geographic area, smoking status, BMI, physical activity, and history of diabetes, hypertension, and hypercholesterolemia. b Reference category.
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Table 2 Distribution of categories of cardiovascular disease (CVD) risk scorea according to different CVD risk factors and regular aspirin use. Italy, 2013. CVD risk score; N (%)
Age (years) b50 50–64 ≥65 Smoking status Non-smokers Current smokers Obesity (BMI ≥ 30 kg/m2) No Yes Hypertension No Yes Hypercholesterolemia (> 200 mg/dl) No Yes Diabetes No Yes Aspirin use No Yes
Low (N = 1499)
Medium (N = 1115)
High (N = 386)
1499 (100.0) – –
81 (7.3) 656 (58.8) 378 (33.9)
12 (3.2) 43 (11.2) 331 (85.7)
1196 (79.8) 303 (20.2)
867 (77.7) 248 (22.3)
321 (83.0) 66 (17.1)
1394 (93.0) 105 (7.0)
944 (84.7) 171 (15.3)
267 (69.2) 119 (30.8)
1476 (98.5) 23 (1.5)
859 (77.0) 256 (23.0)
68 (17.7) 318 (82.3)
1474 (98.3) 25 (1.7)
874 (78.4) 241 (21.6)
88 (22.8) 298 (77.2)
1499 (100.0) –
1115 (100.0) –
251 (65.0) 135 (35.0)
1482 (98.8) 17 (1.2)
993 (89.1) 122 (10.9)
200 (51.7) 187 (48.3)
a Low CVD risk: non-diabetic subjects, aged b50 years, with no more than one of the following risk factors for CVD: i) current smoking; ii) obesity; iii) hypertension; and iv) hypercholesterolemia. High CVD risk: diabetic subjects or subjects aged ≥65 years with at least two of the previously listed risk factors for CVD. Moderate CVD risk: subjects not included among low and high CVD risk categories.
Table 2 shows the distribution of categories of CVD risk score according to different CVD risk factors and regular aspirin use. Aspirin use was 1.2% in participants with a low and 48.3% in participants with a high CVD risk score. Discussion We found that in 2013 approximately 10% of Italian individuals (corresponding to about 5.5 million Italian adults) regularly used aspirin for primary or secondary prevention of CVD. Compared to other highincome countries, aspirin use was substantially higher than that estimated in Switzerland (3.0%) (Rodondi et al., 2008) but much lower than those observed in the USA (over 35%) (Ajani et al., 2006; Pignone et al., 2007). Our prevalence is more than two-fold higher than that observed for regular use in the general Italian adult population in 2002 (Motola et al., 2004). Some discrepancies in terms of sample selection, population age, and deﬁnition of aspirin use do not assure complete comparability between ﬁndings of that study and of our investigation. However, both studies were representative of the general Italian population, and the comparison of such ﬁndings indicated that the prevalence of aspirin regular use consistently increased over the last decade (from 3.4% to 11.2% in men, from 4.9% to 10.5% in women, and from 5.3% to 30.3% in the elderly) (Motola et al., 2004). Moreover, a signiﬁcant increase is also apparent comparing our prevalence with the prevalence of regular users observed in 2005 in a large sample of GP outpatients (8.3%) (Filippi et al., 2011). We observed a higher prevalence of aspirin use among the elderly (over 30%, corresponding to about 3.6 million Italian adults) in 2013. At least other two previous studies found that about 25% of the Italian elderly population regularly used aspirin in 1999 (Pilotto et al., 2003) and 2005 (Filippi et al., 2011). Among diabetics, the prevalence of regular aspirin users was less than 5% in 2002 (Motola et al., 2004) and 38% in 2005 (Filippi et al., 2011), while our study reported a prevalence of over 50% (corresponding to over 1 million Italian adults). Use of aspirin increased from 26.1% in 2005 (Filippi et al., 2011) to over 40% in 2013 among individuals with hypertension (corresponding to about 4.3 million Italian adults). The apparently high prevalence of aspirin use observed among individuals with lower education and physical activity and high level of BMI may be explained by residual confounding by age and other
selected covariates. Accordingly, in our sample, age was highly related to level of education, physical activity, BMI and various comorbidities. Moreover, we found a signiﬁcantly higher aspirin use in central than in northern and southern Italy. The interpretation of this ﬁnding is not simple, and may be due to the interaction of multiple factors, including socio-cultural differences in various geographic macro-areas. Limitations of the present study include those inherent to the crosssectional study design; moreover, there are the self-reported information on regular aspirin use (as well as of previous diagnosis of diabetes, hypertension and hypercholesterolemia) and the limited information on the indication for aspirin use (including clinical history of CVD). However, recall of selected medical conditions has been shown to be satisfactorily reproducible in Italy (Bosetti et al., 2001). The strengths of the study include the sample representativeness of the general Italian adult population. Moreover, the phrasing of our speciﬁc question on aspirin use should have allowed us to exclude from aspirin users those using this drug only sporadically. Using an ad hoc conservative score to categorize participants according to their CVD risk, we identiﬁed 1.2% of low CVD risk individuals (corresponding to over 300 thousand Italian adults) who regularly use aspirin in the Italian population. We cannot derive conclusions for this low-risk population, given the lack of data on clinical indication for aspirin use. More importantly, 52% of individuals with high CVD risk (corresponding to about 3.4 million Italian adults) do not use aspirin for primary or secondary prevention. For this high-risk population, a preventive use of aspirin is recommended, according to international guidelines (Perk et al., 2012; U.S. Preventive Services Task Force, 2009). This high-risk population should therefore be carefully considered by healthcare providers after an individual clinical judgment, and be advised to the use of aspirin once beneﬁts exceed harms (Cuzick et al., 2009; Perk et al., 2012; U.S. Preventive Services Task Force, 2009). Conﬂict of interest statement The authors declare that there are no conﬂicts of interest.
Acknowledgments This study was conducted with the contribution of the Italian Ministry of Health, which had no role in the study design, collection, analysis and
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