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Original article
Estimating Cardiovascular Risk in Spain by the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice Antonio Jesu´s Amor,a Luis Masana,b Federico Soriguer,c,d Albert Goday,e Alfonso Calle-Pascual,f Sonia Gaztambide,c,g Gemma Rojo-Martı´nez,c,d Sergio Valde´s,c,d Ramo´n Gomis,a,c and Emilio Ortegaa,c,* on behalf of [email protected] study group^ a
Servicio de Endocrinologı´a y Nutricio´n, Hospital Clı´nic, IDIBAPS, Barcelona, Spain Unidad de Medicina Vascular y Metabolismo, Hospital Universitario Sant Joan de Reus, Universidad Rovira i Virgili, Reus, Tarragona, Spain c Centro de Investigacio´n Biome´dica en Red de Diabetes y Enfermedades Metabo´licas Asociadas (CIBERDEM), Spain d Servicio de Endocrinologı´a y Nutricio´n, Hospital Universitario Carlos Haya, Ma´laga, Spain e Servicio de Endocrinologı´a y Nutricio´n, Hospital del Mar, Barcelona, Spain f Servicio de Endocrinologı´a y Nutricio´n, Hospital Universitario San Carlos , Madrid, Spain g Grupo de Investigacio´n de Diabetes, Hospital Universitario de Cruces, UPV-EHU, Baracaldo, Vizcaya, Spain b
Article history: Received 19 December 2013 Accepted 13 May 2014
Keywords: Cardiovascular risk European Guidelines on Cardiovascular Disease Prevention in Clinical Practice Systematic Coronary Risk Evaluation Framingham-Registre Gironı´ del Cor
ABSTRACT
Introduction and objectives: There are no nationwide, population-based studies in Spain assessing overall cardiovascular risk. We aimed to describe cardiovascular risk and achievement of treatment goals following the 2012 European Guidelines on cardiovascular disease prevention strategy. We also investigated clinical characteristics (non-classical risk factors) associated with moderate risk. Methods: Participants (n = 2310, 58% women) aged 40 to 65 years from a national population-based study ([email protected] Study) were identified. First, a priori high/very-high risk individuals were identified. Next, total cardiovascular risk (Systematic Coronary Risk Evaluation equation including high-density lipoprotein cholesterol) was used to assess risk of a priori non-high risk individuals. Variables independently associated with moderate versus low-risk were investigated by multiple logistic regression analysis. Results: Age-and-sex standardized (direct method) percentages of high/very-high, moderate, and lowrisk were 22.8%, 43.5%, and 33.7%, respectively. Most men were at moderate (56.2%), while 55.4% of women were at low risk. Low-density lipoprotein cholesterol (< 70, < 100, < 115 mg/dL) and blood pressure ( 65 years) n = 2433 n = 123 Incomplete data to calculate SCORE n = 2310
A priori very high risk (n = 384)
A priori high risk (n = 102)
CVR calculated by SCORE (n = 1824)
• DM (n = 280, 36 with ECV) • Documented CVD (n = 139) • eGFR < 30 (n = 2, 1 with DM)
• DM (n = 48) • eGFR 30-60 (n = 16, 1 with elevated single CVRF) • Elevated single CVRF (n = 41, 2 with DM)
• Low risk (n = 791) • Moderate risk (n = 961) • High risk (n = 69) • Very high risk (n = 3)
Figure 1. Flow chart of study participants. CVD, cardiovascular disease; CVR, cardiovascular risk; CVRF, cardiovascular risk factor; DM, diabetes mellitus, eGFR: estimated glomerular filtration rate; SCORE, Systematic Coronary Risk Evaluation.
obtained and a standard oral glucose tolerance test (in nondiabetics) performed. Serum glucose, triacylglycerols, and cholesterol were measured enzymatically, and HDL-C by direct method. Lowdensity lipoprotein cholesterol (LDL-C) was estimated by the Friedewald formula. Atherogenic dyslipidemia was defined as triglycerides > 150 mg/dL and HDL-C < 40 mg/dL for men and < 45 mg/dL for women. The MDRD (Modification of Diet in Renal Disease) formula was used to estimate glomerular filtration rate. Estimation of Cardiovascular Risk The stepped approach suggested in the European Guidelines on cardiovascular disease prevention in clinical practice was used to estimate CVR in our cohort.3 Flowchart of study participants is shown in Figure 1. First, individuals with a priori very-high risk were identified (n = 384): diabetes (n = 280), either known diabetes (n = 177) or diagnosed after the blood test (n = 103), with one or more CVRF or microalbuminuria (> 20 mg/L); chronic renal failure with estimated glomerular filtration rate 30 ml/ min; or documented CVD. From our questionnaire, 105, 42, and 12 individuals who had coronary heart, cerebrovascular, or peripheral vascular disease, respectively, were identified. Overall, 139 (6.02% total, 3.42% women, 9.63% men) participants had CVD. This prevalence was similar to the one reported in previous studies in a population with similar (35-64 years) age range (6.4% all, 3.9% women and 9.2% men).22 Second, we identified individuals with a priori high risk (n = 102): diabetes (n = 48), either known diabetes (n = 34) or diagnosed after the blood test (n = 14) without other CVRF and without microalbuminuria; estimated glomerular filtration rate between 30 to 60 ml/min; total cholesterol > 8 mmol/L, systolic blood pressure 180 mmHg, or diastolic blood pressure 110 mmHg. For the remaining participants (n = 1824), total CVR was estimated with the current version of the SCORE equation for low-risk regions, which includes HDL-C.23 Finally, very-high (a priori very-high risk or SCORE 10%), high (a priori high risk or SCORE 5%-10%),
moderate (non-high risk and SCORE 1%-5%), and low (non-high risk and SCORE 1%) risk categories were defined. The LDL-C goals according to estimated CVR were defined as: < 130 mg/dL in low, < 115 mg/dL in moderate, < 100 mg/dL in high and < 70 mg/dL in very-high risk individuals.3 Similarly, CVR was estimated by means of the FraminghamREGICOR strategy.5 According to this, individuals with documented CVD were classified as very-high risk, while those with one or more markedly elevated risk factors (total cholesterol > 8 mmol/L, systolic blood pressure 180 mmHg or diastolic blood pressure 110 mmHg) as high risk. For the remaining, total CVR was estimated with the latest (which also includes HDL-C) Framingham-REGICOR equation,5 with values 15% representing very-high, 10-15% high, 5-10% moderate and < 5% low risk. Statistical Analysis Data are presented as median [interquartile range] and number of individuals (percentage) unless otherwise indicated. To estimate total CVR in Spain, standardized rates ( 100 population) of risk categories (low/moderate/high/very-high) were calculated using the direct method described in Armitage et al.24 The age and sex structure of the Spanish population (INE [Instituto Nacional de Estadı´stica], 2010) was used as the standard population. Therefore, our age- and sex-adjusted rates are the rates that would occur if the observed age- and sex-specific rates in the [email protected] study population were present in a population with the age and sex distribution of the standard (INE, 2010) Spanish population. The kappa coefficient was used to examine the agreement between CVR strategies (European Guidelines on cardiovascular disease prevention in clinical practice ans Framingham-REGICOR) in the classification of the participants as very high/high risk vs non– high-risk (moderate/low risk). Differences in age, sex, anthropometric variables, lifestyle, sociodemographic variables, other CVRF, active medications, lipid parameters, and estimated glomerular
˜ a segu´n la guı´a europea sobre prevencio´n Please cite this article in press as: Amor AJ, et al. Estimacio´n del riesgo cardiovascular en Espan de la enfermedad cardiovascular en la pra´ctica clı´nica. Rev Esp Cardiol. 2014. http://dx.doi.org/10.1016/j.recesp.2014.05.023
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filtration rate across the different categories of CVR were evaluated by means of chi-square or Kruskal-Wallis tests as appropriate. Logistic multiple regression analysis was used to investigate CVRF not included in the SCORE equation (ie, non-classical risk factors) that were independently associated with moderate risk (vs low risk). Because most of these factors are age- and sex-dependent, a stepwise multiple logistic regression model adjusted for age, and separate for each sex, was built to investigate variables associated with the moderate risk category. Predictive performance of these models was evaluated by area under the receiver operating characteristic curve and Hosmer-Lemeshow goodness-of-fit test. The significance level was set at P .05. Analyses were performed with SAS software, v.9.2 (SAS Institute Inc.; Cary, North Carolina, United States). RESULTS Prevalence of Cardiovascular Risk Categories In individuals aged 40 to 65 years, CVR estimated by the European Guidelines on cardiovascular disease prevention in clinical practice is mainly moderate (43.4%; 95%CI, 41.4-45.5), and the prevalence of very-high risk is > 15% (Figure 2). Sex differences were found in the SCORE (P < .0001). In men, 56% and 32% were in moderate and high/very-high risk categories, respectively. However, most of the women (55%) were in the lowrisk category and only 4% and 10% of them were at high or veryhigh risk, respectively. Furthermore, diabetes accounted for a large percentage of the high (25% and 35%) and, especially, veryhigh (60% and 69%) risk categories in men and women, respectively.
Cardiovascular Risk Strategies’ Agreement Because individuals with diabetes are a priori defined as a high/ very-high risk in the European Guidelines on cardiovascular disease prevention in clinical practice, but not in Framingham-REGICOR, which includes specific risk estimates for these individuals, we first investigated risk concordance in individuals with diabetes.5 Participants with diabetes (n = 331; 14%) were categorized in the high (n = 48; 15%) or very high (n = 283; 85%) risk category by the European Guidelines on cardiovascular disease prevention in clinical practice and in the low (n = 55, 18%), intermediate (n = 130; 43%), high (n = 54; 18%), or very high (n = 66; 22%) risk category by Framingham-REGICOR. Thereafter, concordance was evaluated in nondiabetic individuals (Tables 1 and 2 of the supplementary material), and because one of the main goals of the CVR prevention strategy is to identify high-risk individuals, our nondiabetic population was dichotomized: individuals at high/very high and at low/moderate risk. After excluding individuals with diabetes, there was a substantial agreement (k = 0.77 [0.73-0.82]) between European Guidelines on cardiovascular disease prevention in clinical practice and Framingham-REGICOR strategies (Table 1). Kappa coefficient was slightly higher for the European Guidelines vs Framingham-REGICOR concordance in women (k = 0.82 [0.750.90]) than in men (k = 0.74 [0.67-0.80]) (Table 1). Treatment Goals Although the proportion of individuals on lipid-lowering, antihypertensive, and antiplatelet drugs increased with increasing risk (all P < .0001), the proportion of those with LDL-C meeting goals or with blood pressure 140/90 mmHg decreased with
A
7.4% (6.4-8.5)
43.4% (41.4-45.5) 15.4% (13.9-17.0)
33.7% (31.7-35.6)
Low
B
Moderate
High
Very high
C 11.1% (10.2-13.7)
30.7% (28.2-33.2)
3.9% (2.9-4.9) 20.9% (18.2-23.6)
10% (8.3-11.7)
56.2% (53.0-59.3)
11.9% (10.2-13.7)
55.4% (52.7-58.0)
Figure 2. Cardiovascular risk estimated by the European Guidelines on cardiovascular disease prevention in clinical practice strategy in population aged 40 to 65 years adjusted to the age and sex structure of the Spanish population (A), men (B) and women (C). Data are shown as percentage and 95% confidence interval.
Please cite this article in press as: Amor AJ, et al. Estimacio´n del riesgo cardiovascular en Espan˜a segu´n la guı´a europea sobre prevencio´n de la enfermedad cardiovascular en la pra´ctica clı´nica. Rev Esp Cardiol. 2014. http://dx.doi.org/10.1016/j.recesp.2014.05.023
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Table 1 Concordance of Estimated Cardiovascular Risk Between Registre Gironı´ del Cor and Systematic Coronary RisK Evaluation in Nondiabetic Population Whole sample (n = 1979) REGICOR
SCORE
Low/moderate risk (n = 1819)
High/very high risk (n = 160)
Low/moderate risk (n = 1752)
1746 (88.2)
6 (0.3)
High/very high risk (n = 227)
73 (3.7)
154 (7.8)
Males (n = 764)a REGICOR
SCORE
Low/moderate risk (n = 657)
High/very high risk (n = 107)
Low/moderate risk (n = 609)
604 (79.1)
5 (0.7)
High/very high risk (n = 155)
53 (6.9)
102 (13.4)
Females (n = 1215)b REGICOR
SCORE
Low/moderate risk (n = 1162)
High/very high risk (n = 53)
Low/moderate risk (n = 1143)
1142 (94)
1 (0.08)
High/very high risk (n = 72)
20 (1.7)
52 (4.3)
REGICOR, Registre Gironı´ del Cor; SCORE; Systematic Coronary RisK Evaluation. Data are expressed as No. (%) of individuals included in each category. a k = 0,74 (95% confidence interval, 0.67-0.80). b k = 0,82 (95% confidence interval, 0.75-0.90).
increasing risk (P < .0001) (Table 2). Only the proportion of individuals with blood pressure 140/90 mmHg was higher (P = .029) among very-high as compared with high-risk individuals, even after adjustment for antihypertensive medication (P = .003). Although the proportion of individuals at very-high risk with LDL-C < 70 mg/dL was very low, this proportion increased to 47% when LDL-C < 100 mg/dL was the cut-off point. Similarly, the proportion of individuals at high or moderate risk with LDL-C < 130 mg/dL was 63% and 69%, respectively. Approximately, one in three (28%-34%) people in moderate, high, and very-high risk categories were smokers (Table 2).
sedentarism and estimated glomerular filtration rate), of the variables shown in Table 3 differed between low and moderate risk individuals. In a stepwise multiple logistic regression model, we found that body mass index (in women), central obesity (in men), diastolic blood pressure, high triglycerides, and low adherence to a Mediterranean diet (in women) were factors associated with moderate risk category (Table 4). This model had good fit based on nonsignificance on the goodness-of-fit Hosmer-Lemeshow test (P = .13 and P = .99 for women and men, respectively, and area under the receiver operating characteristic curves (0.96; 95%CI, 0.95-0.97, and 0.95; 95%CI, 0.93-0.97 for women and men, respectively) indicated good accuracy of predictive models.
Moderate Risk Category DISCUSSION In Table 3, age, sex and several traditional and nontraditional CVRF (which are not a core part of the risk-stratification strategy) are presented by CVR categories. Most, but not all (such as
The [email protected] study18 was designed to determine the prevalence of diabetes and other CVRF in a representative sample of the
Table 2 Treatment Goals According to Estimated Cardiovascular Risk Low risk (n = 791)
Moderate risk (n = 961)
High risk (n = 171)
Very high risk (n = 387)
P
LDL-C, mg/dL
104 [85-104]
118 [99-137]
118 [99-147]
102 [83-120]
< .0001
Lipid-lowering treatment
26 (3.3)
138 (14.3)
18 (10.5)
162 (42)
< .0001
LDL-C meeting goals
645 (81.5)
444 (46.2)
44 (25.9)
57 (14.7)
< .0001
LDL-C
Blood pressure SBP, mmHg
120 [110-129]
134 [123-144]
148 [133-164]
140 [127-152]
< .0001
DBP, mmHg
74 [68-80]
80 [74-86]
84 [78-91]
82 [74-90]
< .0001
Antihypertensive
49 (6.2)
216 (22.5)
50 (29.2)
239 (61.8)
< .0001
BP < 140/90
764 (96.6)
814 (84.7)
116 (67.8)
299 (77.2)
< .0001
128 (25)
296 (30.8)
58 (33.9)
107 (27.7)
6 (0.8)
18 (1.9)
8 (4.7)
108 (28)
Smoking status Current smokers Antiplatelet drugs
.021 < .0001
BP, blood pressure; DBP, diastolic blood pressure; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure. Low-density lipoprotein cholesterol goals according to estimated cardiovascular risk were defined as: < 130 mg/dL for low-risk individuals; < 115 mg/dL moderate-risk individuals; < 100 mg/dL for high-risk individuals, and < 70 mg/dL for very high-risk individuals, respectively. Data are expressed as median [interquartile range] or No. (%).
˜ a segu´n la guı´a europea sobre prevencio´n Please cite this article in press as: Amor AJ, et al. Estimacio´n del riesgo cardiovascular en Espan de la enfermedad cardiovascular en la pra´ctica clı´nica. Rev Esp Cardiol. 2014. http://dx.doi.org/10.1016/j.recesp.2014.05.023
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Table 3 Distribution of Other Classical or Non-classical Cardiovascular Risk Factors According to Estimated Cardiovascular Risk Low risk (n = 791)
Moderate risk (n = 961)
High risk (n = 171)
Very high risk (n = 387)
P
Age, yearsa
45 [42-49]
55 [50-60]b
59 [53-63]
58 [52-62]
REC-1317; No. of Pages 9 Rev Esp Cardiol. 2014;xx(x):xxx–xxx
Original article
Estimating Cardiovascular Risk in Spain by the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice Antonio Jesu´s Amor,a Luis Masana,b Federico Soriguer,c,d Albert Goday,e Alfonso Calle-Pascual,f Sonia Gaztambide,c,g Gemma Rojo-Martı´nez,c,d Sergio Valde´s,c,d Ramo´n Gomis,a,c and Emilio Ortegaa,c,* on behalf of [email protected] study group^ a
Servicio de Endocrinologı´a y Nutricio´n, Hospital Clı´nic, IDIBAPS, Barcelona, Spain Unidad de Medicina Vascular y Metabolismo, Hospital Universitario Sant Joan de Reus, Universidad Rovira i Virgili, Reus, Tarragona, Spain c Centro de Investigacio´n Biome´dica en Red de Diabetes y Enfermedades Metabo´licas Asociadas (CIBERDEM), Spain d Servicio de Endocrinologı´a y Nutricio´n, Hospital Universitario Carlos Haya, Ma´laga, Spain e Servicio de Endocrinologı´a y Nutricio´n, Hospital del Mar, Barcelona, Spain f Servicio de Endocrinologı´a y Nutricio´n, Hospital Universitario San Carlos , Madrid, Spain g Grupo de Investigacio´n de Diabetes, Hospital Universitario de Cruces, UPV-EHU, Baracaldo, Vizcaya, Spain b
Article history: Received 19 December 2013 Accepted 13 May 2014
Keywords: Cardiovascular risk European Guidelines on Cardiovascular Disease Prevention in Clinical Practice Systematic Coronary Risk Evaluation Framingham-Registre Gironı´ del Cor
ABSTRACT
Introduction and objectives: There are no nationwide, population-based studies in Spain assessing overall cardiovascular risk. We aimed to describe cardiovascular risk and achievement of treatment goals following the 2012 European Guidelines on cardiovascular disease prevention strategy. We also investigated clinical characteristics (non-classical risk factors) associated with moderate risk. Methods: Participants (n = 2310, 58% women) aged 40 to 65 years from a national population-based study ([email protected] Study) were identified. First, a priori high/very-high risk individuals were identified. Next, total cardiovascular risk (Systematic Coronary Risk Evaluation equation including high-density lipoprotein cholesterol) was used to assess risk of a priori non-high risk individuals. Variables independently associated with moderate versus low-risk were investigated by multiple logistic regression analysis. Results: Age-and-sex standardized (direct method) percentages of high/very-high, moderate, and lowrisk were 22.8%, 43.5%, and 33.7%, respectively. Most men were at moderate (56.2%), while 55.4% of women were at low risk. Low-density lipoprotein cholesterol (< 70, < 100, < 115 mg/dL) and blood pressure ( 65 years) n = 2433 n = 123 Incomplete data to calculate SCORE n = 2310
A priori very high risk (n = 384)
A priori high risk (n = 102)
CVR calculated by SCORE (n = 1824)
• DM (n = 280, 36 with ECV) • Documented CVD (n = 139) • eGFR < 30 (n = 2, 1 with DM)
• DM (n = 48) • eGFR 30-60 (n = 16, 1 with elevated single CVRF) • Elevated single CVRF (n = 41, 2 with DM)
• Low risk (n = 791) • Moderate risk (n = 961) • High risk (n = 69) • Very high risk (n = 3)
Figure 1. Flow chart of study participants. CVD, cardiovascular disease; CVR, cardiovascular risk; CVRF, cardiovascular risk factor; DM, diabetes mellitus, eGFR: estimated glomerular filtration rate; SCORE, Systematic Coronary Risk Evaluation.
obtained and a standard oral glucose tolerance test (in nondiabetics) performed. Serum glucose, triacylglycerols, and cholesterol were measured enzymatically, and HDL-C by direct method. Lowdensity lipoprotein cholesterol (LDL-C) was estimated by the Friedewald formula. Atherogenic dyslipidemia was defined as triglycerides > 150 mg/dL and HDL-C < 40 mg/dL for men and < 45 mg/dL for women. The MDRD (Modification of Diet in Renal Disease) formula was used to estimate glomerular filtration rate. Estimation of Cardiovascular Risk The stepped approach suggested in the European Guidelines on cardiovascular disease prevention in clinical practice was used to estimate CVR in our cohort.3 Flowchart of study participants is shown in Figure 1. First, individuals with a priori very-high risk were identified (n = 384): diabetes (n = 280), either known diabetes (n = 177) or diagnosed after the blood test (n = 103), with one or more CVRF or microalbuminuria (> 20 mg/L); chronic renal failure with estimated glomerular filtration rate 30 ml/ min; or documented CVD. From our questionnaire, 105, 42, and 12 individuals who had coronary heart, cerebrovascular, or peripheral vascular disease, respectively, were identified. Overall, 139 (6.02% total, 3.42% women, 9.63% men) participants had CVD. This prevalence was similar to the one reported in previous studies in a population with similar (35-64 years) age range (6.4% all, 3.9% women and 9.2% men).22 Second, we identified individuals with a priori high risk (n = 102): diabetes (n = 48), either known diabetes (n = 34) or diagnosed after the blood test (n = 14) without other CVRF and without microalbuminuria; estimated glomerular filtration rate between 30 to 60 ml/min; total cholesterol > 8 mmol/L, systolic blood pressure 180 mmHg, or diastolic blood pressure 110 mmHg. For the remaining participants (n = 1824), total CVR was estimated with the current version of the SCORE equation for low-risk regions, which includes HDL-C.23 Finally, very-high (a priori very-high risk or SCORE 10%), high (a priori high risk or SCORE 5%-10%),
moderate (non-high risk and SCORE 1%-5%), and low (non-high risk and SCORE 1%) risk categories were defined. The LDL-C goals according to estimated CVR were defined as: < 130 mg/dL in low, < 115 mg/dL in moderate, < 100 mg/dL in high and < 70 mg/dL in very-high risk individuals.3 Similarly, CVR was estimated by means of the FraminghamREGICOR strategy.5 According to this, individuals with documented CVD were classified as very-high risk, while those with one or more markedly elevated risk factors (total cholesterol > 8 mmol/L, systolic blood pressure 180 mmHg or diastolic blood pressure 110 mmHg) as high risk. For the remaining, total CVR was estimated with the latest (which also includes HDL-C) Framingham-REGICOR equation,5 with values 15% representing very-high, 10-15% high, 5-10% moderate and < 5% low risk. Statistical Analysis Data are presented as median [interquartile range] and number of individuals (percentage) unless otherwise indicated. To estimate total CVR in Spain, standardized rates ( 100 population) of risk categories (low/moderate/high/very-high) were calculated using the direct method described in Armitage et al.24 The age and sex structure of the Spanish population (INE [Instituto Nacional de Estadı´stica], 2010) was used as the standard population. Therefore, our age- and sex-adjusted rates are the rates that would occur if the observed age- and sex-specific rates in the [email protected] study population were present in a population with the age and sex distribution of the standard (INE, 2010) Spanish population. The kappa coefficient was used to examine the agreement between CVR strategies (European Guidelines on cardiovascular disease prevention in clinical practice ans Framingham-REGICOR) in the classification of the participants as very high/high risk vs non– high-risk (moderate/low risk). Differences in age, sex, anthropometric variables, lifestyle, sociodemographic variables, other CVRF, active medications, lipid parameters, and estimated glomerular
˜ a segu´n la guı´a europea sobre prevencio´n Please cite this article in press as: Amor AJ, et al. Estimacio´n del riesgo cardiovascular en Espan de la enfermedad cardiovascular en la pra´ctica clı´nica. Rev Esp Cardiol. 2014. http://dx.doi.org/10.1016/j.recesp.2014.05.023
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filtration rate across the different categories of CVR were evaluated by means of chi-square or Kruskal-Wallis tests as appropriate. Logistic multiple regression analysis was used to investigate CVRF not included in the SCORE equation (ie, non-classical risk factors) that were independently associated with moderate risk (vs low risk). Because most of these factors are age- and sex-dependent, a stepwise multiple logistic regression model adjusted for age, and separate for each sex, was built to investigate variables associated with the moderate risk category. Predictive performance of these models was evaluated by area under the receiver operating characteristic curve and Hosmer-Lemeshow goodness-of-fit test. The significance level was set at P .05. Analyses were performed with SAS software, v.9.2 (SAS Institute Inc.; Cary, North Carolina, United States). RESULTS Prevalence of Cardiovascular Risk Categories In individuals aged 40 to 65 years, CVR estimated by the European Guidelines on cardiovascular disease prevention in clinical practice is mainly moderate (43.4%; 95%CI, 41.4-45.5), and the prevalence of very-high risk is > 15% (Figure 2). Sex differences were found in the SCORE (P < .0001). In men, 56% and 32% were in moderate and high/very-high risk categories, respectively. However, most of the women (55%) were in the lowrisk category and only 4% and 10% of them were at high or veryhigh risk, respectively. Furthermore, diabetes accounted for a large percentage of the high (25% and 35%) and, especially, veryhigh (60% and 69%) risk categories in men and women, respectively.
Cardiovascular Risk Strategies’ Agreement Because individuals with diabetes are a priori defined as a high/ very-high risk in the European Guidelines on cardiovascular disease prevention in clinical practice, but not in Framingham-REGICOR, which includes specific risk estimates for these individuals, we first investigated risk concordance in individuals with diabetes.5 Participants with diabetes (n = 331; 14%) were categorized in the high (n = 48; 15%) or very high (n = 283; 85%) risk category by the European Guidelines on cardiovascular disease prevention in clinical practice and in the low (n = 55, 18%), intermediate (n = 130; 43%), high (n = 54; 18%), or very high (n = 66; 22%) risk category by Framingham-REGICOR. Thereafter, concordance was evaluated in nondiabetic individuals (Tables 1 and 2 of the supplementary material), and because one of the main goals of the CVR prevention strategy is to identify high-risk individuals, our nondiabetic population was dichotomized: individuals at high/very high and at low/moderate risk. After excluding individuals with diabetes, there was a substantial agreement (k = 0.77 [0.73-0.82]) between European Guidelines on cardiovascular disease prevention in clinical practice and Framingham-REGICOR strategies (Table 1). Kappa coefficient was slightly higher for the European Guidelines vs Framingham-REGICOR concordance in women (k = 0.82 [0.750.90]) than in men (k = 0.74 [0.67-0.80]) (Table 1). Treatment Goals Although the proportion of individuals on lipid-lowering, antihypertensive, and antiplatelet drugs increased with increasing risk (all P < .0001), the proportion of those with LDL-C meeting goals or with blood pressure 140/90 mmHg decreased with
A
7.4% (6.4-8.5)
43.4% (41.4-45.5) 15.4% (13.9-17.0)
33.7% (31.7-35.6)
Low
B
Moderate
High
Very high
C 11.1% (10.2-13.7)
30.7% (28.2-33.2)
3.9% (2.9-4.9) 20.9% (18.2-23.6)
10% (8.3-11.7)
56.2% (53.0-59.3)
11.9% (10.2-13.7)
55.4% (52.7-58.0)
Figure 2. Cardiovascular risk estimated by the European Guidelines on cardiovascular disease prevention in clinical practice strategy in population aged 40 to 65 years adjusted to the age and sex structure of the Spanish population (A), men (B) and women (C). Data are shown as percentage and 95% confidence interval.
Please cite this article in press as: Amor AJ, et al. Estimacio´n del riesgo cardiovascular en Espan˜a segu´n la guı´a europea sobre prevencio´n de la enfermedad cardiovascular en la pra´ctica clı´nica. Rev Esp Cardiol. 2014. http://dx.doi.org/10.1016/j.recesp.2014.05.023
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Table 1 Concordance of Estimated Cardiovascular Risk Between Registre Gironı´ del Cor and Systematic Coronary RisK Evaluation in Nondiabetic Population Whole sample (n = 1979) REGICOR
SCORE
Low/moderate risk (n = 1819)
High/very high risk (n = 160)
Low/moderate risk (n = 1752)
1746 (88.2)
6 (0.3)
High/very high risk (n = 227)
73 (3.7)
154 (7.8)
Males (n = 764)a REGICOR
SCORE
Low/moderate risk (n = 657)
High/very high risk (n = 107)
Low/moderate risk (n = 609)
604 (79.1)
5 (0.7)
High/very high risk (n = 155)
53 (6.9)
102 (13.4)
Females (n = 1215)b REGICOR
SCORE
Low/moderate risk (n = 1162)
High/very high risk (n = 53)
Low/moderate risk (n = 1143)
1142 (94)
1 (0.08)
High/very high risk (n = 72)
20 (1.7)
52 (4.3)
REGICOR, Registre Gironı´ del Cor; SCORE; Systematic Coronary RisK Evaluation. Data are expressed as No. (%) of individuals included in each category. a k = 0,74 (95% confidence interval, 0.67-0.80). b k = 0,82 (95% confidence interval, 0.75-0.90).
increasing risk (P < .0001) (Table 2). Only the proportion of individuals with blood pressure 140/90 mmHg was higher (P = .029) among very-high as compared with high-risk individuals, even after adjustment for antihypertensive medication (P = .003). Although the proportion of individuals at very-high risk with LDL-C < 70 mg/dL was very low, this proportion increased to 47% when LDL-C < 100 mg/dL was the cut-off point. Similarly, the proportion of individuals at high or moderate risk with LDL-C < 130 mg/dL was 63% and 69%, respectively. Approximately, one in three (28%-34%) people in moderate, high, and very-high risk categories were smokers (Table 2).
sedentarism and estimated glomerular filtration rate), of the variables shown in Table 3 differed between low and moderate risk individuals. In a stepwise multiple logistic regression model, we found that body mass index (in women), central obesity (in men), diastolic blood pressure, high triglycerides, and low adherence to a Mediterranean diet (in women) were factors associated with moderate risk category (Table 4). This model had good fit based on nonsignificance on the goodness-of-fit Hosmer-Lemeshow test (P = .13 and P = .99 for women and men, respectively, and area under the receiver operating characteristic curves (0.96; 95%CI, 0.95-0.97, and 0.95; 95%CI, 0.93-0.97 for women and men, respectively) indicated good accuracy of predictive models.
Moderate Risk Category DISCUSSION In Table 3, age, sex and several traditional and nontraditional CVRF (which are not a core part of the risk-stratification strategy) are presented by CVR categories. Most, but not all (such as
The [email protected] study18 was designed to determine the prevalence of diabetes and other CVRF in a representative sample of the
Table 2 Treatment Goals According to Estimated Cardiovascular Risk Low risk (n = 791)
Moderate risk (n = 961)
High risk (n = 171)
Very high risk (n = 387)
P
LDL-C, mg/dL
104 [85-104]
118 [99-137]
118 [99-147]
102 [83-120]
< .0001
Lipid-lowering treatment
26 (3.3)
138 (14.3)
18 (10.5)
162 (42)
< .0001
LDL-C meeting goals
645 (81.5)
444 (46.2)
44 (25.9)
57 (14.7)
< .0001
LDL-C
Blood pressure SBP, mmHg
120 [110-129]
134 [123-144]
148 [133-164]
140 [127-152]
< .0001
DBP, mmHg
74 [68-80]
80 [74-86]
84 [78-91]
82 [74-90]
< .0001
Antihypertensive
49 (6.2)
216 (22.5)
50 (29.2)
239 (61.8)
< .0001
BP < 140/90
764 (96.6)
814 (84.7)
116 (67.8)
299 (77.2)
< .0001
128 (25)
296 (30.8)
58 (33.9)
107 (27.7)
6 (0.8)
18 (1.9)
8 (4.7)
108 (28)
Smoking status Current smokers Antiplatelet drugs
.021 < .0001
BP, blood pressure; DBP, diastolic blood pressure; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure. Low-density lipoprotein cholesterol goals according to estimated cardiovascular risk were defined as: < 130 mg/dL for low-risk individuals; < 115 mg/dL moderate-risk individuals; < 100 mg/dL for high-risk individuals, and < 70 mg/dL for very high-risk individuals, respectively. Data are expressed as median [interquartile range] or No. (%).
˜ a segu´n la guı´a europea sobre prevencio´n Please cite this article in press as: Amor AJ, et al. Estimacio´n del riesgo cardiovascular en Espan de la enfermedad cardiovascular en la pra´ctica clı´nica. Rev Esp Cardiol. 2014. http://dx.doi.org/10.1016/j.recesp.2014.05.023
G Model
REC-1317; No. of Pages 9 A.J. Amor et al. / Rev Esp Cardiol. 2014;xx(x):xxx–xxx
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Table 3 Distribution of Other Classical or Non-classical Cardiovascular Risk Factors According to Estimated Cardiovascular Risk Low risk (n = 791)
Moderate risk (n = 961)
High risk (n = 171)
Very high risk (n = 387)
P
Age, yearsa
45 [42-49]
55 [50-60]b
59 [53-63]
58 [52-62]
