Blood pressure control in the year following coronary events

International Journal of Cardiology 130 (2008) 205 – 210 www.elsevier.com/locate/ijcard

Blood pressure control in the year following coronary events Jacqueline Müller-Nordhorn a,⁎, Heinz Völler b , Andrea Pfennig a , Sylvia Binting a , Karl J. Krobot c , Stefan N. Willich a a

Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany b Rehabilitation Center for Cardiovascular Diseases, Rüdersdorf, Germany c MSD Sharp & Dohme, Haar, Germany Received 4 February 2007; received in revised form 23 July 2007; accepted 3 August 2007 Available online 3 December 2007

Abstract Background: Blood pressure control is often insufficient in secondary prevention. The objective of the present study was to determine predictors for long-term elevated blood pressure (BP) in patients after coronary events. Methods: Patients were included at admission to inpatient cardiac rehabilitation. A total of 18 cardiac rehabilitation centers in Germany participated. Indications for admission were myocardial infarction (MI), coronary artery bypass grafting (CABG), or percutaneous transluminal coronary angioplasty (PTCA). The duration of follow-up was 12 months. Risk factors, medication, and clinical events were assessed from patients and their physicians. Results: A consecutive sample of 1907 men (mean age 60 ± 10 years) and 534 women (mean age 65 ± 10 years) was admitted; the 12-month follow-up rate was 85%. Of all patients, 38% had a BP ≥ 140 and/or ≥90 mmHg at admission to the rehabilitation center compared to 48% at the 12-month follow-up. Patients with diabetes were less likely to achieve BP b 140/90 mmHg compared to patients without diabetes (43% vs. 56%; P b 0.001). In multivariable analyses, significant predictors for elevated BP after 12 months were baseline BP ≥140/90 mmHg (RR 2.5; 95% CI 1.7, 3.7), diabetes (RR 2.2; 95% CI 1.4, 3.5), and indication for admission (MI vs. CABG RR 0.6; 95% CI 0.4, 1.0, and PTCA vs. CABG RR 0.5; 95% CI 0.2, 1.0). Conclusions: Long-term blood pressure control is not satisfactory in about half of the patients following coronary events. Particularly, patients with diabetes appear to be at risk for elevated blood pressure. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Blood pressure; Diabetes; Secondary prevention; Coronary heart disease

1. Introduction Current guidelines recommend the reduction of blood pressure levels below 140/90 mmHg in all patients at high risk [1–3]. High-risk patients are defined either as patients at high risk of a cardiovascular event or as patients who already have a history of coronary heart disease and/or stroke in the European guidelines. A risk of cardiovascular death of more than 5% in the next 10 years is defined as a high risk according to the risk ⁎ Corresponding author. Charité University Medical Center, Luisenstr, 57, D-10117 Berlin, Germany. Tel.: +49 30 450 529026; fax: +49 30 450 529902. E-mail address: [email protected] (J. Müller-Nordhorn). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.08.042

estimations based on the Systematic Coronary Risk Evaluation (SCORE) project [4,5]. In patients with diabetes, the recommended blood pressure level is even below 130/ 80 mmHg. These recommendations are based on several meta-analyses and large randomised controlled trials showing that the effective reduction in both systolic and diastolic blood pressure significantly lowers cardiovascular morbidity and mortality [6–11]. Although there is no consensus on the most effective antihypertensive drug or combination of drugs to use, the achievement of the target blood pressure levels is a major goal in the prevention of cardiovascular diseases. However, a number of studies have shown that there is a clear gap between recommendations and their translation into daily practice [12–14]. In secondary prevention following

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coronary events, for example, the EUROASPIRE studies I and II found that the proportion of patients with elevated blood pressure levels (≥140/90 mmHg) was 55% and 54% in 1995– 96 and 1999–2000, respectively [12]. These studies have been based on previous guidelines, as a time interval needs to be taken into account between the publication and distribution of a guideline and its implementation into routine care by the medical community [15–17]. However, current guidelines are similar to previous guidelines, which also recommend blood pressure levels below 140/90 mmHg for all patients and b 130/ 80 mmHg or 130/85 mmHg for patients with diabetes. This is based on the publication of several large randomised controlled trials showing that aggressive lowering of blood pressure levels is even more important in patients with diabetes [18–20]. Overall, it is important to identify those patients at particular risk for elevated blood pressure in the long-term follow-up. The objective of the present study was, therefore, to assess blood pressure control in the year following coronary events, with focus on patients with diabetes, and to determine early predictors for elevated blood pressure.

laboratory analyses, electrocardiograms (ECGs) and exercise ECGs during the rehabilitation therapy. In addition, selfadministered questionnaires were given to the patients at admission to, and on the day of discharge from, the rehabilitation centre. In the baseline questionnaire, patients were asked about cardiac risk factors, lifestyle, employment status, medication, and socio-economic factors including the postal code of their area of residence. Follow-up questionnaires were sent to patients by mail at 6 and 12 months in order to assess recurrent clinical events, lifestyle, employment status, medication, and outpatient rehabilitation. In addition, the patients' general practitioners were contacted after 12 months to provide standardized information as to medication, risk factors including blood pressure, coronary events and interventions of their patients during the follow-up period. In order to assess total mortality, a letter was sent to those patients lost to follow-up inquiring about their general state of health. Additionally, we contacted their general practitioners and, if necessary, the vital records offices. 2.3. Statistical analysis and data management

2. Methods 2.1. Design and setting The Post Infarction Care (PIN) Study was designed as a prospective multi-centre study, which examined recurrent clinical events, cardiac risk factors, employment status, and medication after inpatient cardiac rehabilitation [21–23]. The follow-up period was 12 months. The design of the study and results as to the occurrence of clinical events including cardiovascular death, myocardial infarction, revascularisation, and angina pectoris and/or congestive heart failure with hospitalisation during the follow-up period were previously published [21]. In the PIN Study, patients were included consecutively at admission to one of the 18 participating rehabilitation centres in Germany. Primary indications for cardiac rehabilitation were myocardial infarction, coronary artery bypass grafting (CABG), or percutaneous transluminal coronary angioplasty (PTCA). Exclusion criteria were refusal by the patient, language or mental barriers, and medical conditions leading to direct readmission to acute care. In Germany, inpatient cardiac rehabilitation is routinely offered to patients after myocardial infarction and CABG by social legislation. Patients usually stay in a rehabilitation centre for 3 weeks. The inpatient rehabilitation programme includes exercise therapy, health education, physiotherapy, psychological support, and relaxation therapy. The study was approved by the Ethics Committee of the Charité University Medical Center; it conforms to the principles embodied in the Declaration of Helsinki.

Baseline characteristics, blood pressure levels and medication after 12 months were compared between patients with and without diabetes. The t test was used for the comparison of continuous variables, and the chi-squared test for the comparison of categorical variables. Elevated blood pressure was defined as a blood pressure ≥140 and/or ≥90 mmHg [15]. Logistic regression analysis was used to determine predictors for the dependent variable blood pressure ≥140/90 mmHg after 12 months. The model was adjusted for age and sex; the following variables were entered into the model: smoking, education (N/≤10 years), employment status prior the acute event (working yes/no), type of work (blue- versus white-collar worker), income (b1000 €, 1000–1749 €, ≥1750 €), living with a partner (yes/no), region of residence (East vs. West Germany), indication for admission (myocardial infarction, CABG, or PTCA), blood pressure at baseline (≥/b 140/ 90 mmHg), diabetes (either a history of diabetes and/or a blood glucose level ≥7 mmol/l at admission to the rehabilitation center vs. none), body mass index (kg/m2), LDL (low density lipoprotein) cholesterol (mmol/l), physical and mental SF-36 summary scores, exercise ECG (watt) at the rehabilitation center, and the New York Heart Association (NYHA) functional classes. The model was derived by backwards stepwise regression analysis. All tests for significance were two-sided; the significance level was α = 0.05. Statistical analyses were performed using SPSS, version 10.0 for windows (SPSS Inc, Chicago). 3. Results

2.2. Assessments at baseline and follow-up 3.1. Study population Blood pressure was recorded at admission to and at discharge from the rehabilitation center by the rehabilitation physicians as well as the results of physical examinations,

Between January and July 1997, a total of 2441 patients were eligible for the PIN study and consented to participate.

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92% (n = 2233) of the patients returned the questionnaire after 6 months and 85% (n = 2069) after 12 months. We contacted general practitioners to get additional information about the patients included in the study after 12 months; the response rate was 63% (n = 1536). Of all patients, 78% were men with a mean age of 60 ± 10 years, and 22% women with a mean age of 65 ± 10 years. A history of diabetes and/or a fasting blood glucose ≥ 7 mmol/l at admission to the rehabilitation center was assessed in 26% of patients. Table 1 compares socio-economic factors and baseline clinical variables as well as physical and mental SF-36 summary scale scores in patients with and without diabetes. 3.2. Blood pressure at baseline and after 12 months In all patients, mean systolic and diastolic blood pressure at baseline was 130 mmHg and 78 mmHg, respectively. At follow-up, mean systolic and diastolic blood pressure was Table 1 Baseline characteristics and recurrent clinical events during follow-up in patients with and without diabetes Variables a

No diabetes (n = 1703)

Socioeconomic factors Mean age (SD) 59 years (11) Women 19% Education (N10 years) (%) 12% Living alone (%) 83% Blue-collar worker (%) 50% Employed (%) 48% Income (%) b1000 € 27% 1000–1749 € 41% ≥1750 € 32% Residence in East Germany 24% Risk factors Smoking 42% Systolic BP (SD) 128 mmHg (21) Diastolic BP (SD) 78 mmHg (12) LDL cholesterol (SD) 3.8 mmol/l (1.1) Blood glucose (SD) 5.3 mmol/l (0.7) Body mass index (SD) 27 kg/m2 (3) Indication for admission Myocardial infarction 60% CABG 34% PTCA 6% SF-36 summary scales Physical (SD) 44 (11) Mental (SD) 44 (14) Exercise ECG (SD) 100 W (36) Congestive heart failure (%) No congestive heart failure 47% NYHA I 27% NYHA II 21% NYHA III/IV 5% Recurrent clinical events 38%

Diabetes (n = 622)

p-value

63 years (9) 30% 12% 80% 53% 30%

b0.001 b0.001 0.879 0.063 0.148 b0.001

36% 41% 24% 35%

b0.001 b0.001

31% 132 mmHg (21) 77 mmHg (11) 3.7 mmol/l (1.2) 8.4 mmol/l (3.8) 28 kg/m2 (4)

b0.001 b0.001 0.588 0.003 b0.001 b0.001

47% 47% 5%

b0.001

40 (11) 42 (14) 84 W (33)

b0.001 0.034 b0.001

36% 24% 29% 12% 38%

b0.001 0.879

a For continuous variables, mean values and SDs are given; BP, blood pressure; CABG, coronary artery bypass grafting; ECG, electrocardiogram; LDL, low density lipoprotein; NYHA, New York Heart Association (functional classes); PTCA, percutaneous transluminal coronary angioplasty; SD, standard deviation; SF-36, Short Form-36.

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Table 2 Blood pressure (BP) levels in all patients and different subgroups at the 12month follow-up Patient subgroups

≥140/ Mean systolic 90 mmHg BP (SD)

Mean diastolic BP (SD)

All patients Men Women b60 years 60–69 years ≥70 years No diabetes Diabetes BP b140/90 mmHg baseline BP ≥ 140/90 mmHg baseline Indication for admission Myocardial infarction CABG PTCA

48% 48% 49% 43% 48% 59% 44% 57% 40% 60%

134 mmHg (16) 133 mmHg (16) 135 mmHg (17) 131 mmHg (16) 135 mmHg (16) 137 mmHg (17) 132 mmHg (16) 137 mmHg (16) 130 mmHg (16) 139 mmHg (17)

80 mmHg (9) 81 mmHg (9) 79 mmHg (8) 81 mmHg (9) 80 mmHg (8) 79 mmHg (9) 80 mmHg (9) 81 mmHg (8) 79 mmHg (9) 82 mmHg (9)

44% 55% 40%

132 mmHg (17) 80 mmHg (9) 136 mmHg (16) 81 mmHg (8) 130 mmHg (16) 80 mmHg (10)

BP, blood pressure; CABG, coronary artery bypass grafting; PTCA, percutaneous transluminal coronary angioplasty; SD, standard deviation.

134 and 80 mmHg, respectively. Table 2 depicts the percentage of patients with elevated blood pressure (≥ 140/ 90 mmHg) after 12 months as well as mean systolic and diastolic blood pressure levels in various patient subgroups. Patients with diabetes had significantly higher systolic mean blood pressure levels compared to patients without diabetes both at baseline and follow-up (P b 0.001) (Tables 1 and 2). There was no significant difference with regard to mean diastolic blood pressure levels at baseline and follow-up. Of patients with diabetes, 43% had a blood pressure below 140/ 90 mmHg and 11% below 130/80 mmHg. Factors associated with elevated blood pressure levels after 12 months were elevated blood pressure levels at baseline, the prevalence of diabetes, lower LDL cholesterol levels, and indication for admission (Table 3). There was no Table 3 Predictors at baseline for elevated blood pressure (≥140/90 mmHg) after 12 months Variables

Relative risk

95% CI

p-value

Age [per year increase] Women ≥140/90 mmHg at baseline LDL cholesterol (mmol/l) Diabetes⁎ Indication for admission CABG (reference) PTCA Myocardial infarction NYHA classification No congestive heart failure NYHA I NYHA II NYHA III/IV

1.013 1.015 2.488 0.816 2.164

0.994, 1.033 0.585, 1.760 1.671, 3.703 0.684, 0.975 1.351, 3.466

0.183 0.958 b0.001 0.025 0.001

1 0.452 0.600

0.206, 0.991 0.391, 0.992

0.034 0.047 0.020

1 1.853 1.356 1.247

1.177, 2.916 0.811, 2.266 0.510, 3.048

0.065 0.008 0.246 0.629

⁎Defined as either having a history of diabetes and/or a fasting plasma glucose ≥7 mmol/l; CABG, coronary artery bypass grafting; CI, confidence interval; LDL, low density lipoprotein; NYHA, New York Heart Association (functional classes); PTCA, percutaneous transluminal coronary angioplasty.

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Table 4 Prescription of antihypertensive-acting medication at the 12-month followup in patients with and without diabetes Medication⁎

No diabetes Diabetes p-value

β-blockers ACE inhibitors Calcium antagonists Diuretics Nitrates Any antihypertensive-acting medication⁎

80% 54% 12% 27% 29% 88%

71% 68% 16% 38% 28% 90%

b0.001 b0.001 0.018 b0.001 0.740 0.394

⁎One or more antihypertensive medication (β-blockers, ACE inhibitors, calcium antagonists, diuretics, nitrates) prescribed independent from the indication; ACE, angiotensin converting enzyme.

significant association with socio-economic factors, other risk factors, or other clinical variables. 3.3. Medication At the 12-month follow-up, 95% of all patients were prescribed at least one antihypertensive-acting drug such as βblockers, ACE (angiotensin converting enzyme) inhibitors, diuretics, calcium antagonists, or nitrates. Table 4 shows the percentage of patients with and without diabetes receiving the respective antihypertensive drugs. Patients with diabetes were significantly more likely to receive ACE inhibitors, calcium antagonists, and diuretics compared to patients without diabetes but were less likely to receive β-blockers.

compliance with guidelines and the lack of patients' compliance with the recommendations of their physicians. Phillips et al. summarized the lack of physicians' compliance with guidelines in a review [24]. In their opinion, so-called ‘clinical inertia’ describes the failure of health care providers to initiate or intensify therapy when indicated. Clinical inertia is due to at least three problems: overestimation of care provided; use of “soft” reasons to avoid intensification of therapy; and lack of education, training, and practice organization aimed at achieving therapeutic goals. In a US survey of 139 primary care clinicians treating patients with hypertension, 68% estimated that their patients had blood pressures levels b140/90 mmHg, whereas these targets were only met by 43% of patients [25]. Apart from physician compliance, adherence of patients with lifestyle measures and medication is an important issue. Only an estimated 50% of patients are taking their medication as prescribed by their physician [26]. Although adherence to medication is higher in secondary compared to primary prevention, asymptomatic diseases such as hypertension or hypercholesterolemia are associated with decreased adherence compared to symptomatic diseases [27]. Reasons for lack of adherence include primary prevention setting, increasing age, male sex, as well as an increasing number of prescribed drugs and treating physicians [28]. 4.2. Risk of diabetes and hypertension combined

4. Discussion In about half of the patients, the recommended blood pressure levels below 140/90 mmHg following coronary events are not achieved. Patients with diabetes, lower LDL cholesterol levels, as well as patients with an already elevated blood pressure at baseline are particularly at risk for elevated blood pressure at follow-up. In patients with diabetes, the gap between recommendations of guidelines and usual care is even larger with about only one tenth of diabetic patients achieving the recommended blood pressure level below 130/80 mmHg. 4.1. Adherence to guidelines in both physicians and patients Our study confirms the results of cross-sectional studies such as the EUROASPIRE I and II studies which have also shown a lack of risk factor control in patients with coronary heart disease [12]. In the EUROASPIRE studies, similarly, blood pressure was controlled only in about half of all patients. Despite the clear evidence of the clinical benefit of blood pressure control in the secondary prevention setting with reduced morbidity and mortality, there appear to be barriers to the implementation of research findings into the usual care situation [7,9,10]. Barriers to the implementation of research findings and clinical guidelines into routine care as well as to the achievement of target levels include the lack of physicians'

The coexistence of diabetes doubles the risk of cardiovascular events and mortality in hypertensive patients, as described in a systemic review by Grossman et al. [29]. However, particularly patients with diabetes were at risk for lack of blood pressure control in our study and the recommended target of blood pressure below 130/ 80 mmHg was achieved in only 11% of patients [2,13,15]. The recommended target blood pressure in patients with diabetes is based on large clinical trials showing an increased benefit of diabetic patients with tighter blood pressure control [19,20,30]. In the Hypertension Optimal Treatment (HOT) study including 18,790 patients from 26 countries, there was a 51% reduction in major cardiovascular events in patients with diabetes mellitus when comparing the target group with diastolic blood pressure ≤80 mmHg to the group ≤ 90 mmHg (p for trend = 0.005) [19]. In addition, the United Kingdom Prospective Diabetes Study (UKPDS) showed that lowering blood pressure in diabetic patients is not only associated with a reduced rate of macrovascular complications but is also successful in preventing microvascular complications [20]. Indeed, control of high blood pressure appears to be more effective in reducing cardiovascular in patients with diabetes than tight glycemic control [31]. However, similarly to our study, the HERS study found that in women with coronary heart disease, established drugs for secondary prevention such as aspirin, β-blockers, and lipidlowering agents were underused in all women but

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particularly in those at highest risk and with the highest number of risk factors [32]. Effective antihypertensive agents in type 2 diabetes include ACE inhibitors, angiotensin-receptor blockers, diuretics, β-blockers, and calcium-channel blockers [33]. In our study, we observed a different pattern in the prescription of antihypertensive patients in patients with compared to those without diabetes with less β-blockers prescribed. Physicians may be reluctant to prescribe βblockers or diuretics in the context of studies such as the Antihypertensive and Lipid-Lowering treatment to Prevent Heart Attack Trial (ALLHAT) or the Losartan Intervention for Endpoint reduction in hypertension (LIFE) Study [34]. In patients with diabetes, these studies showed a significant advantage of antihypertensive therapy with ACE inhibitors and angiotensin II antagonists compared to β-blockers and diuretics. While diuretics or beta-adrenoceptor antagonists may worsen insulin resistance and impair glucose tolerance, antihypertensive agents exert neutral or even slightly positive metabolic effects. 4.3. Limitations of the study In Germany, inpatient cardiac rehabilitation is routinely offered to all patients after myocardial infarction and coronary artery bypass grafting. Following myocardial infarction, approximately two-thirds of all patients participate in an inpatient cardiac rehabilitation program [35]. However, we do not have any information about patients who refused inpatient cardiac rehabilitation in our study as we included patients at the time of admission to the rehabilitation centre. A selection bias cannot be excluded, as those patients who refuse inpatient cardiac rehabilitation may be different from the total group. Rauch et al. showed in their registry that patients not being transferred to cardiac rehabilitation tend to be older, to have had a previous myocardial infarction and/or diabetes mellitus, and to be less likely to have had acute revascularization [35]. The results of our cohort can, therefore, only be generalized to patients following inpatient cardiac rehabilitation in Germany. In addition, patients after PTCA are not routinely offered inpatient rehabilitation. This explains the comparatively low number of patients with PTCA in our study. Patients with PTCA in our study may not be representative, as they may have been transferred to cardiac rehabilitation because of high comorbidity and/or complications following the intervention. 5. Conclusion Long-term blood pressure control following coronary events is not sufficient in about half of the patients. It is, therefore, important to identify those patients particularly at risk for elevated blood pressure in the long term. Especially patients with diabetes appear to be at risk for increased blood pressure levels at follow-up. Potential explanations range from physiological differences between patients with and

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without diabetes in the context of the metabolic syndrome to differences in medication patterns. Increased efforts should be taken to reach target blood pressure levels in patients with diabetes. Further research should focus on the underlying reasons for the observed differences and investigate new treatment options as well as improvements in the management of these high-risk patients in the usual care situation. Acknowledgements We would like to thank all the patients, the physicians of the participating rehabilitation centers as well as the general practitioners who contributed to the study. The steering committee included Völler H, Willich SN, Gohlke H, Hahmann H, Kleber FX, Krobot K, and Bestehorn K. We would also like to thank Merck, Sharp & Dohme for the unconditional funding of the study.

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