Abstract
J Clin Hypertens (Greenwich). 2012;00:00–00. ©2012 Wiley Periodicals, Inc.
The benefit obtained from antihypertensive treatment is related more to overall cardiovascular risk reduction than to blood pressure levels. Accurate implementation of cardiovascular diagnostics is a key step toward assessment of cardiovascular risk. In the 3A Registry study, data about patient history, concomitant diseases, diagnostic procedures, and medications were prospectively collected. A total of 14,738 patients recruited by 899 physicians in 2008 and 2009 were analyzed. Assessment of cardiovascular risk factors and subclinical end‐organ damage (SOD) showed broad differences in the implementation of European Society of Hypertension/European Society of Cardiology recommendations. Electrocardiograms were available in 59% of patients, cholesterol in 71.4%, and glucose in 69.7%. Almost all patients (99.6%) had creatinine measurements performed and microalbuminuria was measured in 8.5%. Metabolic syndrome (MS) had been evaluated in 59.7%. Implementation of diagnostic guidelines was highest in hypertensive patients with diabetes, followed by patients with known cardiovascular disease and established chronic renal insufficiency. For hypertensive patients without known comorbidities, the authors estimated that up to 29% had missed SOD (detection rate <50%) and 13% missed MS due to incomplete assessment of risk factors. This large registry study shows that assessment for cardiovascular risk factors and SOD is incomplete. Major efforts are required to improve comprehensive hypertension management as recommended by current guidelines.
Hypertension is a single variable in overall cardiovascular (CV) risk. Age, sex, obesity, diabetes, dyslipidemia, proteinuria, and renal function factor in the risk assessment. 1 The absolute benefit obtained from blood pressure (BP)–lowering treatment is related more to overall CV risk than to individual BP levels. 2 To help physicians assess risk, the European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines 2007 were published. 3 The societies emphasized the importance of subclinical target‐organ damage, since patients with “no complaints” comprise most of the hypertensive population. The occurrence of major CV events is preceded by the development of asymptomatic structural and functional abnormalities at the vascular, renal, and cardiac level. 4 Carotid intimal‐media thickness 5 and ankle‐brachial index (ABI) are useful in assessing subclinical risk. 6 Serum creatinine, glomerular filtration rate (GFR) estimates, and microalbuminuria are also helpful in this regard. 7 , 8 , 9 Cardiac left ventricular hypertrophy can be measured by electrocardiography or echocardiography. 10 , 11 , 12 According to ESH/ESC guidelines, the following routine investigations are recommended: electrocardiography for assessment of cardiac, albuminuria and creatinine for renal and ABI for vascular target‐organ damage, blood chemistry for fasting glucose, total cholesterol, low‐density lipoprotein (LDL) cholesterol, high‐density lipoprotein (HDL) cholesterol, triglycerides (fasting), uric acid, potassium, hemoglobin and hematocrit, serum creatinine, and urine analysis. 3 The guidelines have also determined that the available facilities determine the amount of screening. 3 On one hand, searching for target‐organ damage and determining other risk factors is a time‐consuming and expensive endeavor. On the other hand, high‐ or very high‐risk profile patients warrant immediate pharmacologic therapy and perhaps risky technical prophylactic interventions. 3 , 13 Several studies suggest that BP control in Germany is not adequate 14 , 15 , 16 ; however, no study to date has investigated how well physicians are following ESC/ESH guidelines. German law allows no indirect assessment (reviewing results of third‐party payers). Furthermore, the health care system, albeit enviable, is not amenable to medical record review. Our objective was to conduct an assessment of how subclinical end‐organ damage and CV risk factor evaluation is performed in German clinical outpatient practice.
Methods
The 3A Registry
The details of the design and the baseline variables of the 3A Registry are published elsewhere. 17 In brief, the 3A Registry is a prospective, observational, noninterventional, multicenter cohort study. It was initiated in August 2008 by the Institut für Herzinfarktforschung (http://www.herzinfarktforschung.de) in Ludwigshafen, Germany, with ongoing follow‐up at the time of publication of this article. Physicians in primary care throughout Germany were invited for participation, if they decided on the initiation or modification of antihypertensive therapy of their patients. Prescribing of the drugs was in accordance with governing German regulations and reimbursement criteria, and neither drug was provided for the participants. All patients had to provide written informed consent before inclusion into the registry. The protocol was approved by the local medical ethical committee, Mainz, Germany. It has been registered in Clinicaltrials.gov under NCT01454583 and the VfA database on noninterventional studies.
The exclusion criteria were a foreseeable problem to perform follow‐up visits and failure to provide consent.
The 3A Registry had several objectives. The first goal was to characterize consecutive outpatients with newly diagnosed or known hypertension in Germany and to assess their comorbidities such as heart failure, diabetes, or renal failure. We were particularly interested in the documentation of diagnostic procedures and description of guideline adherence in the use of diagnostic procedures and treatments in hypertensive German outpatients.
The data were collected through a Web‐based standardized questionnaire with plausibility checks. In 10% of the patients, an audit with on‐site monitoring of the source data was performed.
Data Collection and Entry
All data, if available, were collected during the clinical examination or from the review of the patient chart. Data were recorded at inclusion (baseline) and during the follow‐up visits. Patients were defined as having diabetes when they had known (and treated) diabetes mellitus or glycosylated hemoglobin ≥6.5% based on American Diabetes Assocation guidelines. 19
Statistical Methods
All summaries were presented on available data. Categorical data were described as the number and percentage of patients in each category. The calculation of percentages did not include missing data. The analysis was performed with SAS version 9.2 (SAS Institute, Inc, Cary, NC). Prediction of number of patients with undiagnosed risks was performed using R (R Development Core Team (2011). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3‐900051‐07‐0, http://www.R‐project.org/).
Results
The 3A Registry included 14,988 patients. A total of 14,738 patients had enough information about baseline characteristics and diagnostic procedures to be included in the following analysis. Figure 1 indicates broad differences in the implementation of recommendations, with 99.6% of all patients receiving creatinine measurement, while only 8.5% had microalbuminuria determined. While 71.4% of patients had their total cholesterol measured, LDL and HDL were available in only slightly more than half of the patients (Table I). Physicians chose to document the 12‐lead electrocardiographic results in 59% of patients.
Figure 1.
Current level of application of routine test according to European Society of Cardiology (ESC) guidelines (left panel); usage of measures for subclinical end organ damage (right panel).
Table I.
Current Level of Application of Routine Test According to ESC and Tests Relevant for Prognosis of Subclinical End‐Organ Damage
| Clinical Variable | Total (N=14,738), No. (%) | Hypertension Only (n=6578), No. (%) | CVD (n=4614), No. (%) | DM (n=4242), No. (%) | CKD (n=3252), No. (%) |
|---|---|---|---|---|---|
| Glucose | 10,268 (69.7) | 4358 (66.3) | 3346 (72.5) | 3466 (81.7) | 2170 (66.7) |
| Total cholesterol | 10,517 (71.4) | 4526 (68.8) | 3431 (74.4) | 3403 (80.2) | 2225 (68.4) |
| LDL‐C | 8171 (55.4) | 3265 (49.6) | 2839 (61.5) | 2910 (68.6) | 1766 (54.3) |
| HDL‐C | 7940 (53.9) | 3223 (49) | 2715 (58.8) | 2795 (65.9) | 1693 (52.1) |
| Triglycerides | 8799 (59.7) | 3633 (55.2) | 2967 (64.3) | 2978 (70.2) | 1896 (58.3) |
| Waist circumference | 4839 (32.8) | 1978 (30.1) | 1600 (34.7) | 1676 (39.5) | 1018 (31.3) |
| Albumin (urine) | 1248 (8.5) | 324 (4.9) | 472 (10.2) | 687 (16.2) | 382 (11.7) |
| ECG | 8691 (59) | 3620 (55) | 3113 (67.5) | 2590 (61.1) | 1943 (59.7) |
| eGFR | 14673 (99.6) | 6578 (100) | 4573 (99.1) | 4204 (99.1) | 3252 (100) |
| ABI | 1151 (7.8) | 428 (6.5) | 448 (9.7) | 392 (9.2) | 273 (8.4) |
Abbreviations: ABI, ankle‐brachial index; DM, diabetes mellitus; CKD, chronic kidney disease; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; ECG, electrocardiography; ESC, European Society of Cardiology; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol.
The rates of patients with evaluation of potential subclinical target‐organ damage are shown in Figure 1. ABI was performed in <10%. Waist circumference and C‐reactive protein, which are not included in the current guidelines, were somewhat more commonly recorded at 33% and 15%, respectively.
When analyzing the level of compliance with ESC recommendations in subgroups of hypertensive patients based on already established CV disease, chronic renal insufficiency, and diabetes mellitus (high‐risk patients), the pattern was hardly different, as shown in Figure 2. In general, patients with diabetes mellitus had a slightly more thorough workup, compared with hypertensive patients without known target‐organ damage. We next wanted to estimate the prevalence of subclinical target‐organ damage in hypertensive patients without comorbidities. About 54% of these patients were assessed for the presence of left ventricular hypertrophy. Left ventricular hypertrophy was present in 15% of those tested. For microalbuminuria, reduced GFR, and reduced ABI, the prevalence of pathological values was 30%, 0%, and 5%, respectively. Among patients without appropriate diagnostics, a number of patients with end‐organ damage have to be expected. The size of this risk group was dependant on the prevalence of the respective pathology as well as the level of application of diagnostic procedures. We approximated how many additional patients would be expected to be affected. This simplified extrapolation gives raw estimates of the magnitude of the problem, albeit not as exact as a diagnostic study in this population. The results are shown in Figure 2 and Table II. Applying the ratio of pathological vs normal to the hypertension‐only patients in whom no electrocardiogram was performed led to an estimate of 7% of all hypertensive patients with left ventricular hypertrophy that went undiagnosed. In patients with microalbuminuria, this estimate increased up to 29%. In patients who had an ABI value <0.9, indicating probable target‐organ damage, 0.4% of patients were known to be affected while another 4.8% were expected to fall into that category, so that <10% of all abnormal results were detected. In patients with an estimated GFR <60 mL/min, the detection rate was at an almost ideal value, with 0% of patients testing positive and no patients expected to be affected but untested.
Figure 2.
Level of application of routine test according to European Society of Cardiology (ESC) guidelines in subgroups defined by pathology (left panel); prevalence of subclinical end‐organ damage in hypertensive patients free of cardiovascular disease, chronic renal insufficiency, and diabetes mellitus (hypertension‐only), as well as expected prevalence in those patients who were not tested (right panel).
Table II.
Observed and Expected Rate of Pathological Findings Indicating Subclinical Target‐Organ Damage, Based on Level of Application
| Condition | Tested Normal | Tested Abnormal | Untested, Expected Normal | Untested, Expected Abnormal |
|---|---|---|---|---|
| LVH, % | 46.58 | 7.91 | 38.91 | 6.6 |
| Microalbuminuria | 3.42 | 1.51 | 66.02 | 29.05 |
| GFR, % | 100 | 0 | 0 | 0 |
| ABI | 6.17 | 0.33 | 88.69 | 4.81 |
Abbreviations: ABI, ankle‐brachial index; GFR, glomerular filtration rate; LVH, left ventricular hypertrophy.
ESH/ESC guidelines recommend that the components of the metabolic syndrome be tested in all hypertensive patients, as shown in Figure 3 and Table I. While hypertension is present in the total study population by definition, the remaining diagnostic criteria for the metabolic syndrome were only casually documented. Waist circumference, a test that requires no cost and is performed in approximately 20 seconds, was measured in 30%, and the remaining diagnostic criteria are measured only partially as well: glucose in 66%, HDL cholesterol in 49%, and triglyceride concentrations in 55%. Again, there were considerable differences between groups defined by the different comorbidities. Similar to assessment of subclinical target‐organ damage, evaluation of the metabolic syndrome was best performed in patients with diabetes, where the diagnosis is irrelevant. Metabolic syndrome is supposed to identify those patients at risk for diabetes mellitus, rather than those who already have the condition.
Figure 3.
Level of measured application for metabolic syndrome in subgroups defined by abnormal findings (left panel); prevalence of indicators for metabolic syndrome in hypertensive patients free of cardiovascular disease, chronic renal insufficiency, and diabetes mellitus (hypertension‐only), as well as expected prevalence in those without proper measurements (right panel).
For the entire cohort, adequate diagnostic testing for the metabolic syndrome was performed in 9267 patients. Of those patients, 5162 patients (55.7%) met metabolic syndrome criteria. Next, we calculated the expected rate of undetected metabolic syndrome in the hypertension‐only patients, as shown in Figure 2 and Table III. The results indicate that metabolic syndrome was missed in a large group, comprising 13% of patients.
Table III.
Observed and Expected Rate of Pathological Findings Indicating Subclinical Target‐Organ Damage, Based on Level of Application
| Condition | Tested Normal | Tested Abnormal | Untested, Expected Normal | Untested, Expected Abnormal |
|---|---|---|---|---|
| Waist circumference | 19.1 | 11.0 | 44.4 | 25.5 |
| Glucose | 63.1 | 3.2 | 32.1 | 1.6 |
| HDL‐C, % | 40.0 | 9.0 | 41.6 | 9.4 |
| Triglycerides | 28.8 | 26.4 | 23.3 | 21.5 |
| Metabolic syndrome | 40.3 | 19.4 | 27.2 | 13.1 |
Abbreviation: HDL‐C, high‐density lipoprotein cholesterol.
Discussion
This is one of the first reports about the adherence to guidelines in the assessment of CV risk in outpatients with hypertension. We found that the evaluation of CV risk factors and subclinical target‐organ damage for the majority of hypertensive patients is often not in line with current recommendations.
Diagnostic assessment was lowest in hypertensive patients without known comorbidities. In patients without comorbidities, in whom diagnostic assessment was not performed, up to 30% are expected to have subclinical target‐organ damage and 13% to have the metabolic syndrome, which would place them into the high‐risk category.
The more intense the diagnostic approach, the higher the percentage of patients with correctly identified risk. The more extensive the diagnostic workup performed by physicians, the higher the percentage of correctly identified patients at risk. 19 In this context, Cuspidi and colleagues 11 observed that the routine search for cardiac and vascular subclinical target‐organ damage, based on the ultrasound evaluation for left ventricular hypertrophy and intimal‐media thickness, allows the reclassification of up to 50% of all patients, previously classified as presenting with low‐ or medium‐risk to high‐ or very high‐risk status.
Systematic evaluation of hypertensive patients with all the examinations recommended by the ESH/ESC guidelines is not a routine practice. Gomez‐Marcos and colleagues 20 showed that nearly 25% of low‐ and medium‐risk hypertensive patients had to be reclassified to the high‐ or very high‐risk group. Assessment of electrocardiographic left ventricular hypertrophy assessment, ABI, and estimated GFR reclassified a significant higher number of hypertensive patients to the high‐risk category as compared with Framingham risk prediction tools. 21 In the setting of hypertension, several registries have shown a prevalence of electrocardiographic criteria for left ventricular hypertrophy of 10% to 20%, with a prevalence of kidney damage of 20% to 30%. 22 Viazzi and associates showed that the prevalence of microalbuminuria, left ventricular hypertrophy, and carotid intimal‐media thickening or carotid plaque presence was 13%, 49%, and 32%, respectively. 23 The combined use of microalbuminuria and cardiac and vascular ultrasonography led to the detection of a significantly higher patient percentage at high or very high risk. Redon and coworkers 24 showed that the prevalence of CV disease is inversely proportional to the level of renal function in hypertensive patients from primary care. The subgroup of patients with microalbuminuria was much more likely to harbor target‐organ damage than were patients with left ventricular hypertrophy or carotid abnormalities. 25 Our data show that assessment for subclinical target‐organ damage was lowest in hypertensive patients without overt diabetes, CV disease, or chronic renal insufficiency. The physicians treated these patients as if they had low risk. For these patients, however, a thorough assessment to determine their total CV risk is desperately needed. Thus, these “misclassified” patients are at risk for not having the optimal treatment strategies available to them.
Specifically, in patients with hypertension and diabetes mellitus, subclinical target‐organ damage testing identifies patients at very high CV risk. In the Losartan Intervention For Endpoint Reduction (LIFE) study that evaluated patients with hypertension and electrocardiographic left ventricular hypertrophy, mortality during a follow‐up period of 5 years was 14%. 26 The mortality was even greater among patients with albuminuria. 27 In our cohort, electrocardiographic testing was performed in 61% and microalbuminuria was sought in only 16% of hypertensive patients with diabetes mellitus.
Several studies have shown that measuring microalbuminuria is an attractive and cost‐effective screening test that is especially suitable as the first step in the large‐scale diagnostic workup of hypertensive patients. 19 , 23 Due to its low cost and widespread availability, this test has been included in the current guidelines. Nevertheless, this approach was used in only a minority of hypertensive patients in our cohort.
Intensified diagnostic evaluation in general practice improves the prognosis of patients. 25 Ultrasonographic evaluation of cardiac and vascular structures is a sensitive tool for detecting high‐risk patients and may have a significant impact on risk profile. Existing barriers for overcoming these obvious gaps between current scientific recommendations and their implementation into primary care should be identified and removal strategies defined. One reason for the limited implementation of pertinent guidelines might be that patients with hypertension are commonly older and present with multiple problems. Rather than the lack of knowledge or enthusiasm among health care providers, the major difficulty in complying with complex guidelines could be that existing guidelines or models almost exclusively focus on single medical conditions. Following such guidelines for each medical condition among multi‐morbid patients may often appear not feasible or even tolerable for patients and the caring physicians. 28 Therefore, scientific guidelines should explicitly accentuate patients with multiple chronic diseases for whom special conditions such as drug interactions or reduced renal clearance must be taken into account. In the near future, the increasing prevalence of hypertension likely will not be paralleled by the availability of financial resources for prevention. 29 Therefore, practical implications of diagnostic and therapeutic strategies at the community level are needed.
German authorities should be encouraged to improve adherence to the guidelines for evaluation and treatment of hypertension. Disease management programs (DMPs) have been implemented for several chronic diseases in Germany; however, a DMP for hypertension is lacking. A DMP for hypertension would facilitate standardized diagnosis, evaluation, and treatment and care processes for hypertensive patients in Germany. Furthermore, the importance of continuing medical education could be strengthened so that the lack of knowledge on hypertension can be overcome. The implementation of a Hypertension Specialist by the German Hypertension League with a structured education progress, examination, and continuing mandatory education has been an important step.
Limitations
Registries enable a real‐world estimation of actual disease diagnostic strategies and treatments; however, our registry had several limitations. Physicians volunteered to participate, so presumably they were at least interested in improving care of hypertensive patients. We can only speculate how physicians who had no such interest would perform. Presumably the performance of such physicians is worse. Furthermore, coding of medical diagnoses and diagnostic workup in our study was based only on clinical appraisal, albeit validated by objective criteria in an audit of 10% of the patients.
Conclusions
Primary care physicians who manage hypertensive patients still miss opportunities in assessing CV risk. In patients receiving medications for hypertension, insufficient attention is paid to concomitant treatable risk factors that are at least as important as BP. These are the presence of diabetes mellitus, lipid disturbances, and decreased renal function. In addition, simple measures of the individual atherosclerotic risk profile of the patient and simple detectors of subclinical target‐organ damage such as electrocardiographic presence of left ventricular hypertrophy and microalbuminuria are not used. To improve the prognosis of hypertensive patients, an improvement in risk assessment is clearly needed.
Disclosure: Novartis Pharma GmbH supported the 3A registry.
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