Abstract
Objective. To determine the proportion and clinical features of unrecognized heart failure (HF) in hypertensive women ≥65 years attended in Spain. Methods. A cross-sectional study carried out in primary healthcare setting. Patients were considered to present unrecognized clinical diagnosis of HF if they had not been previously diagnosed but fulfilled Framingham criteria for HF diagnosis. Results. Of 3500 patients, the proportion of unrecognized clinical HF was 26.3%. In comparison with women without HF, all cardiovascular risk factors were more prevalent in patients with unrecognized HF; the same was observed for target organ damage, being the most frequent left ventricular hypertrophy (LVH) (54.1% vs 15.5%, p<0.0001), and for the presence of cardiovascular disease, being the most common coronary heart disease (24.8% vs 9.8%, p<0.0001). Predictive factors associated with the presence of unrecognized HF were LVH (OR =4.84) and the presence of previous cardiovascular disease (OR =2.26) Blood pressure control was worse in patients with unrecognized HF (16.6% vs 33.9%, p <0.01). Conclusions. More than a quarter of hypertensive women ≥65 years may have clinical data of unrecognized HF. Hypertensive women with unrecognized clinical HF have a worse clinical profile and worse BP control rates than those without HF.
Introduction
Arterial hypertension is a main cardiovascular (CV) risk factor, and its occurrence has been associated with the presence of heart failure (HF). In fact, it has been estimated that about 50% of the patients with uncontrolled blood pressure (BP) may develop HF and that risk for developing HF in hypertensive compared with normotensive subjects is about twofold in men and threefold in women (Citation1,Citation2). On the other hand, about three-quarters of patients with HF are hypertensive (Citation3). As a result, ACC/AHA guidelines for the diagnosis and management of chronic HF have included hypertension as stage A by structural abnormality according to ACC/AHA recommendations (Citation4). This states that hypertensive patients are at risk of developing HF (Citation5), what has been recently confirmed in the current ESC guidelines (Citation5).
The prevalence of HF has increased in the last decades because of the progressive ageing of the population, the better treatment of patients with acute coronary events and the improvement in secondary prevention (Citation5–7). In Europe, the prevalence of HF is about 2–3%, increasing in parallel with age (Citation8). Thus, it has been calculated a prevalence between 10–20% in 70–80-year-old people (Citation5,Citation8). In younger subjects, HF is more frequent in men, but in the elderly, the prevalence of HF is equalled for both genders (Citation5).
Cardiovascular disease (CVD) is the most important cause of death among women, HF being one of the most important aetiologies (Citation8,Citation9). Despite that, it seems that many physicians and patients do not actually perceive the real risk of HF in women (Citation10). This could be, at least partially, related to the confidence in the well-known cardio-protective effect of female hormones, but also to the fact that, in the past decades, most clinical trials included principally male patients (Citation11,Citation12). Fortunately, in the last few years, an increased sensitivity on this issue is growing (Citation13).
The best approach to reduce the incidence and mortality of HF is its early diagnosis and treatment (Citation4–6). However, in many cases, clinical detection of HF in hypertensive population is uneasy, particularly in elderly women. In this context, this study was performed to determine the proportion, clinical profile and management of elderly hypertensive women with unrecognized clinical diagnosis of HF.
Methods
For this purpose, an epidemiological, cross-sectional and multicenter survey was performed. Patients were included from June 2007 to December 2007. A total of 1066 general practitioners all around Spain participated in the study. Each investigator was asked to include the first five consecutive outpatients that attended the clinic and met the inclusion criteria. The inclusion criteria were: women ≥65 years old with an established diagnosis of arterial hypertension and with a written informed consent provided. Subjects with a recent diagnosis of hypertension (<6 months) were excluded.
The main objective of the study was to assess the proportion of unrecognized clinical HF in elderly hypertensive women daily attending in a primary care setting in Spain. To determine the clinical attitude of physicians, the BP control rate and the clinical profile according to the presence of unrecognized HF were the secondary endpoints.
The presence of clinical HF was defined according to the Framingham criteria for HF diagnosis (Citation14). Diagnosis of HF according to Framingham criteria requires the simultaneous presence of at least two major criteria or one major criterion in conjunction with two minor criteria. Major criteria include: paroxysmal nocturnal dyspnea; neck vein distention; rales; radiographic cardiomegaly; acute pulmonary oedema; S3 gallop; hepatojugular reflux; and weight loss > 4.5 kg in 5 days in response to treatment. Minor criteria include: bilateral ankle oedema; nocturnal cough; dyspnoea on ordinary exertion; hepatomegaly; pleural effusion; and tachycardia (heart rate >120 beats/min).
Unrecognized HF was considered when patients fulfilled the Framingham criteria but they did not have been previously diagnosed of HF. The bio-demographic data, risk factors, defined according to European 2003 hypertension guidelines (Citation15), the history of CVD and the current treatments were collected. The presence of organ damage or CVD was recorded from the patients’ clinical history. The diagnosis of left ventricular hypertrophy (LVH) was established by either electrocardiogram (Sokolow–Lyons >38 mm; Cornell >2440 mm×ms); and/or echocardiogram (left ventricular mass index ≥125 [male], ≥110 [female] g/m2) according to the definition of 2003 European guidelines (Citation15). Smoking was defined when consumption of ≥1 cigarette/day and ex-smoker when quitting smoking in the 12 months before this survey was performed. Excessive alcohol intake was considered a weekly consumption of the equivalent of 26 oz (769 ml) of 40-proof alcohol. Sedentary lifestyle was defined as the physical activity lesser than a 30-min daily walk. Waist circumference was measured at the midway point between the iliac crest and the costal margin. Obesity was considered when the body mass index was >30 kg/m2 and abdominal obesity when the waist circumference was >88 cm.
BP readings were taken following the European guidelines, with the patient in a seated position and the back supported, and after 5 min resting, using calibrated mercury sphygmomanometers or validated automatic devices according to availability (Citation16). The patients were advised to avoid smoking or drinking coffee within 30 min prior to BP assessment. The visit BP was the average of two separate measurements taken by the examining physician, a third measure was obtained when there was a difference ≥5 mmHg between the two readings and the average of the two last ones recorded. Adequate BP control was defined as <140/90 mmHg (<130/80 mmHg for diabetics and chronic kidney disease) (Citation15).
Statistical analysis
The primary endpoint assessed to calculate the sample size was the proportion of unrecognized clinical HF according to Framingham criteria in elderly hypertensive women. Since there was no available data about this variable, it was assumed as the maximum uncertainty (p0=0.5), as this was the most conservative attitude. The proportion of hypertensive women ≥65 years with unrecognized HF was calculated from the binomial distribution, with a 95% confidence interval. A sample size of 4235 was estimated to calculate the primary variable with a precision of ±1.5% and a 95% confidence interval. It was assumed that 15% of patients would not be valid for the analysis. As a result, a final simple size of about 5000 patients was calculated.
Normal distribution was tested by the Kolmogorov–Smirnov test. Continuous variables, which were expressed as mean (SD), were compared using the Student t-test for paired and unpaired data or analysis of variance (ANOVA) when indicated. Categorical variables, expressed as a percentage, were compared with the chi-square test or the Fisher exact test when appropriate. To determine the main factors involved in unrecognized HF, a multivariate analysis (stepwise backward) was performed. Bio-demographic data, CV risk factors, target organ damage, CVD, BP values and antihypertensive drugs were included as potential predictive factors. Database design was subjected to internal consistency rules and ranges to control inconsistencies/inaccuracies in the collection and tabulation of data. Statistical significance was set at a p-value <0.05. The statistical analysis was carried out using the SAS statistics package, version 9.1.3 (Chicago, Illinois, USA).
Results
A total of 5047 patients were consecutively recruited for the study; 740 were excluded because they did not meet the inclusion criteria. Additionally, 807 patients were also excluded as they had a previous diagnosis of HF. Of 3500 patients, the proportion of unrecognized clinical HF was 26.3%. The clinical profile of the study population was compared according to the presence of unrecognized HF or no HF (). In comparison with hypertensive women without HF, all CV risk factors were more prevalent in those with unrecognized clinical HF; the same was observed for target organ damage, the most frequent being LVH (54.1% vs 15.5%, p<0.0001), and for the presence of previous CVD, the most common being coronary heart disease (24.8% vs 9.8%, p < 0.0001). A total of 46.2% of the patients with unrecognized clinical HF and 33.4% of those without HF were diabetic, and 16.3% and 6.6%, respectively were on atrial fibrillation (p<0.0001). In the multivariate analysis, the main factors associated with the presence of unrecognized HF were LVH (OR =4.84), and the presence of previous CV or renal disease (OR=2.26). Other predictors are shown in . According to Framingham criteria, the most prevalent major criteria were cardiomegaly (27%), rales (9.5%) and paroxysmal nocturnal dyspnoea (8.0%), and the most common minor criteria were ankle oedema (48.4%) and dyspnoea on exertion (40.0%) ().
Figure 1. Proportion of major and minor criteria of Framingham for the diagnosis of heart failure.
Table I. Clinical profile of the study population according to the presence of unrecognized heart failure or no heart failure.
Table II. Predictive factors involved in unrecognized heart failure.
BP was worse controlled in patients with unrecognized clinical HF (16.6%) than in those without HF (33.9%), p<0.01 (). Treatments are shown in . Antihypertensive combined therapy were more commonly used in patients with unrecognized clinical HF (77.1%) vs patients without HF (56.5%), p< 0.0001. Diuretics, angiotensin-converting enzyme inhibitors, beta-blockers, aldosterone antagonists, antiplatelets, anticoagulants, nitrates, digoxine, antiarrhythmic agents, statins and antidiabetics were more frequently used in patients with previously unrecognized clinical HF.
Figure 2. Blood pressure control rates. HF, heart failure.
Table III. Medication according to the presence of unrecognized heart failure or no heart failure.
After fulfilment of the Framingham criteria, physicians considered it necessary to ask for complementary tests in 91.9% of patients when HF was suspected (80.2% echocardiogram, 69.6% electrocardiogram and 65.8% chest X-ray) vs 34.85% when it was not (p<0.0001), to refer the patient to a specialist in 66.4% (88.7% to cardiology and 10.7% to internal medicine) vs 11.4%, respectively (p < 0.0001), and to modify the treatment in 66.2% vs 32.5%, respectively (p< 0.005) ().
Table IV. Diagnostic procedures performed according to the suspicion of heart failure.
Discussion
It has been reported that long-term mortality in HF has declined in the last decades, particularly in men, and more for ischaemic than for non-ischaemic HF. Unfortunately, this decline has reduced in the current century (Citation16). As a result, long-term mortality after a first hospitalization for HF remains high. Several reasons may explain this. A continuous improvement in HF secondary prevention has occurred in ischaemic HF rather than in other non-ischaemic HF (Citation5). Since the management of acute coronary syndromes (more frequent in men) has markedly improved, it is likely that an increase in the incidence of no-ischaemic HF, and a relative decrease of new onset ischaemic HF have appeared in the last few years (Citation5). To improve the prognosis of HF patients, an early diagnosis is mandatory. Unfortunately, many physicians do not suspect HF, and this is particularly relevant in the elderly and in women, as this study confirms. Our data showed that the proportion of hypertensive women ≥65 years with unrecognized clinical HF was about 26%. Guidelines recognize that the accuracy of HF diagnosis only by clinical means is often inadequate, particularly in women, in the elderly and in obese subjects, three conditions that are frequently combined in HF clinical conditions (Citation4,Citation5). Although the Framingham criteria were published some decades ago and are well known and applied (Citation14), it seems that they are actually underused. When a disease is not detected, physicians may delay the treatment and the prognosis may worsen. Taking into account the high proportion of elderly hypertensive women with unrecognized clinical HF, it is likely that this could play a role in the lack of survival improvement reported in females with HF in the last few years (Citation16).
The first step for the identification of patients with HF is clinical suspicion. In this sense, the data provided from this survey could be clinically relevant, since it may help to identify which hypertensive women are more sensitive to clinical HF. Comparing with hypertensive patients without HF, all CV risk factors, target organ damage and previous CVD were more frequent in subjects with clinical HF. Moreover, in the multivariate analysis, predictors of unrecognized HF were LVH (OR=4.60), the concomitance of CVD (OR=2.60) and coronary heart disease (OR=2.07). Previous studies have reported that, compared with men, women hospitalized with HF are older, have a higher prevalence of arterial hypertension, less coronary disease and more co-morbid conditions (Citation17,Citation18). This information may help in the early identification of clinical HF. Therefore, in clinical practice, in all hypertensive women with any other co-morbidity, physicians should be aware of the possibility of clinical HF. The identification of this population and an early diagnosis of HF appear crucial to improve the common bad prognosis of this devastating disease.
Interestingly, unrecognized HF has translated into worse clinical management as BP control rates showed. If HF is not recognized, the risk perception decreases and a minor number of treatments are prescribed. This is important, since it has recently been demonstrated that even in normotensive systolic BP values, there is a linear relationship between BP levels and HF risk, emphasizing the need to achieve BP goals to prevent HF (Citation19). The poorer clinical management is not just limited to BP control rates, but physicians’ attitude as well. Although general practitioners referred most subjects with suspected HF to a specialist, they only modified the treatment in six out of 10 patients, and were not rigorous enough when asking for complementary tests. As an example, about 80% and <10% of the patients performed an echocardiogram or determination of brain natriuretic peptides, respectively – two essential diagnostic procedures for HF diagnosis (Citation4,Citation5).
Finally, a great proportion of elderly hypertensive women with HF have preserved systolic function. This condition is associated with a high morbidity and mortality (Citation20,Citation21). This could be explained not only by the lack of a well established evidence-based therapy (Citation22), but also by the high proportion of female patients with HF who are undiagnosed and subsequently untreated, which may translate into a worse prognosis. The data provided from this survey could support more information about this entity and help physicians to better identify this population and facilitate an early diagnosis.
Some limitations must be disclosed for this study. The cross-sectional design was chosen to represent best the “real world” of clinical practice; consequently, a large hypertensive population recruited by consecutive sampling was included in the trial. However, this methodology has its limitations, since it reduces the level of control that can be exercised to reduce variation and bias. However, the number of patients included and the nature of the evaluated endpoints, with no comparators under review, minimize this theoretical limitation. The objective of the study was to assess the proportion of unrecognized clinical HF according to Framingham criteria, but not to determine the actual proportion of definite HF. In fact, to be diagnosed with HF, patients should have not only typical HF clinical symptoms and signs, but also objective evidence of a structural or functional abnormality of the heart at rest, as the guidelines establish (Citation6). On the other hand, our study was carried out in a population attended by general practitioners in Spain; the data could probably only be generalized to those countries with the same healthcare delivery and CV risk profile.
In conclusion, more than a quarter of hypertensive women aged ≥65 years may have clinical data of unrecognized HF. In comparison with hypertensive without HF, all CV risk factors, target organ damage and CVD were more frequent in patients with unrecognized clinical HF. Moreover, they exhibited worse BP control. Physicians referred most of the patients with suspected HF to a specialist, modified the treatment only in six out of 10 patients of them and were not rigorous enough when asking for complementary tests. These results highlight the need for ongoing medical education to improve early recognition of HF in the female hypertensive population, with the goal of reducing overall CV risk.
Acknowledgments
The authors wish to express their deepest gratitude to all investigators who actively participated in this study. The present study was supported by an unrestricted grant provided by Almirall S.A., Barcelona, Spain. All data have been recorded and analysed independently to prevent bias. The authors have no relevant conflict of interest to disclose.
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