Obesity is associated with numerous risk factors and comorbidities such as hypertension, metabolic syndrome, type 2 diabetes, and cardiovascular diseases. However, numerous studies have reported an obesity paradox; the overweight and obese patients with established cardiovascular disease have better prognosis than those with a BMI <25 kg/m2. This study was designed to assess potential differences in the clinical profile and management of hypertensive outpatients with chronic ischemic heart disease in obese and lean patients that could explain these two apparently contradictory points. Overweight and obesity were defined as a BMI 25–29.9 kg/m2 and ≥30 kg/m2, respectively. Cardiovascular risk factors goals were considered according to European Society of Hypertension-European Society of Cardiology 2003, National Cholesterol Education Program Adult Treatment Panel III and American Diabetes Association 2005 guidelines. A sample of 2,024 patients (66.8 ± 10.1 years; 31.7% women) was included. Of these, 0.1% had a BMI <20 kg/m2; 17.1% BMI 20–24.9 kg/m2; 53.7% BMI 25–29.9 kg/m2; 23.7% BMI 30–34.9 kg/m2; 4.3% BMI 35–39.9 kg/m2; and 1.1% BMI ≥40 kg/m2. The subgroup of patients with BMI ≥30 kg/m2 had a higher proportion of women, diastolic dysfunction, diabetes, dyslipidemia, left ventricular hypertrophy, and heart failure. There was an inverse relationship between risk factors control rates and BMI (all comparisons BMI 20–24.9 kg/m2 vs. 25–29.9 kg/m2 vs. ≥30 kg/m2): blood pressure (BP) control (51.7% vs. 42.4% vs. 29.2%, P < 0.001); low-density lipoprotein cholesterol (LDL-C) control (35.2% vs. 30.5% vs. 27.9%, P = 0.03) and diabetes control (38.6% vs. 27.6% vs. 22.2%, P = 0.023). In conclusion, in patients with hypertension and chronic ischemic heart disease, as BMI increases, the clinical profile worsens as well as risk factors control rates.
Obesity is becoming a global epidemic not only in adults, but more concerning in children (1). This condition is associated with numerous risk factors and comorbidities such as hypertension, metabolic syndrome, type 2 diabetes, cardiovascular diseases, sleep apnea/sleep-disordered breathing and also with certain cancers (1,2). Although BMI is the most common parameter used to study obesity, other parameters such as the waist circumference, used to assess abdominal obesity, are clinically meaningful as well (3). Thus, an European study that included nearly 360,000 patients reported that both general and abdominal obesity were associated with risk of death (4).
Obesity is a growing critical problem in the United States, where nearly 70% of adults are now classified as overweight or obese, compared with <25% identified 40 years ago (3,5). Moreover, the proportion of subjects with morbid obesity has increased by a greater extent than overweight and mild obesity (3,6). The World Health Organization has estimated that >1 billion people are overweight worldwide, and whether the current trend continues, this proportion will increase to 1.5 billion by 2015 (7,8). As a result, healthcare service use and medical costs related with obesity will raise in the following years (1,9).
Obesity not only worsens metabolic profile, but a variety of adaptations/alterations in cardiac structure and function occur in obese patients, even in the absence of other comorbidities (1). Heart may be affected by obesity through the increased prevalence of cardiovascular risk factors, such as hypertension, dyslipidemia, or glucose intolerance, but also due to the prothrombotic and inflammatory state that happens in this situation (1,10,11). All these factors predispose or increase the possibility of developing coronary heart disease, heart failure, and sudden death (1,2,6). However, despite these adverse associations are unquestionable, numerous studies have reported an obesity paradox as obese patients with heart disease exhibited a better prognosis that their counterparts with lower BMI (7,12,13,14,15,16,17,18).
CINHTIA (Cardiopatía Isquémica crónica e Hipertensión Arterial en la práctica clínica en España) was a cross-sectional and multicentre survey aimed to determine the clinical profile and management of hypertensive patients with chronic ischemic heart disease in daily practice across Spain (19,20,21). The aim of our study was to assess whether there were differences in the clinical profile and management of hypertensive outpatients with chronic ischemic heart disease according to BMI.
Methods and Procedures
A total of 112 investigators, all cardiologists, participated in this multicenter study performed during the second quarter of 2006. To best represent the clinical practice in Spain, the investigators who participated in the study belonged to different primary, secondary, and tertiary health care cardiology centers. Each investigator was asked to include consecutively patients ≥18 years, both genders, with an established diagnosis of hypertension and chronic ischemic heart disease. Patients with an acute coronary syndrome within the previous 3 months were excluded. The study was approved by an ethics committee and before being enrolled, patients provided a written informed consent.
The biodemographic data, risk factors, history of cardiovascular disease and treatments were recorded for every patient. All patients underwent a complete physical examination and a blood test, including hematology and biochemistry with a complete lipid profile, what could be performed within the previous 6 months. The data were recorded and stored in a central and independent clinical research organization (Biometrica, Barcelona, Spain).
Hypertension was considered when blood pressure (BP) was ≥140/90 mm Hg (130/80 mm Hg, for diabetic patients) or a documented history of hypertension and taking antihypertensive medication. Chronic ischemic heart disease was defined as the presence of stable angina, history of myocardial infarction, evidence of myocardial ischemia or previous revascularization (surgical or percutaneous). Overweight was defined as a BMI between 25 and 29.9 kg/m2 and obesity as BMI ≥30 kg/m2 (22). Abdominal obesity was considered as a waist circumference >102/88 cm (men/women).
The presence of target organ damage or associated clinical conditions was recorded from the patients' clinical history. All of them were defined according to the European Society of Hypertension-European Society of Cardiology 2003 guidelines (23). Left ventricular hypertrophy was considered either by electrocardiogram (Sokolow–Lyons >38 mm; Cornell >2,440 mm × ms) or echocardiography (left ventricular mass index ≥125 g/m2 in men and 110 in women).Renal impairment as a serum creatinine between 1.3 and 1.5 mg/dl (115–133 µmol/l) in men and 1.2–1.4 mg/dl (107–124 µmol/l) in women. Diabetes was considered when fasting plasma glucose was >126 mg/dl (7.0 mmol/l), postprandial plasma glucose > (198 mg/dl (11.0 mmol/l) or patient was on antidiabetics (oral or insulin). The history of peripheral artery disease, heart failure and stroke were considered only when a clinical inform that confirmed these conditions were available. Diastolic dysfunction was defined according to the mitral filling pattern. Sedentary lifestyle was defined as the physical activity shorter than a 30 min daily walk.
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 mercury sphygmomanometers or validated automatic devices according to availability (23). The patients were advised to quit 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 of ≥5 mm Hg between the two readings. Waist circumference was measured at the mid-way point between the iliac crest and the inferior costal margin.
BP control was defined as systolic BP <140 mm Hg and diastolic BP <90 mm Hg (<130 and <80 mm Hg for diabetic patients and patients with chronic kidney disease) (23). Low-density lipoprotein cholesterol (LDL-C) <100 mg/dl was considered as good control (24). Adequate glycemic control rates were defined following the American Diabetes Association (ADA) recommendations (25).
Several statistical tests were performed depending on the nature of variables being compared. Comparison of continuous variables between groups was performed using the Student's t-test and the analysis of variance test. The χ2-test was used to analyze the relationship between categorical variables. A logistic regression analysis was performed to determine which factors could be associated with BP control. Clinical characteristics of study population (age, gender, BMI, abdominal obesity), cardiovascular risk factors (dyslipidemia, smoking, diabetes, sedentary life style), organ damage (left ventricular hypertrophy, heart failure, peripheral artery disease, renal impairment, stroke), antihypertensive treatment (β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, antagonist receptor blockers, diuretics, α-blockers), concomitant treatments (lipid lowering drugs, oral antidiabetics drugs, insulin), and biochemical parameters (total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides, serum fasting glucose, creatinine, uric acid) were included as independent variables in the logistic regression analysis. A P value <0.05 was used as the level of statistical significance. Database recording was subjected to internal consistency rules and ranges to control inconsistencies/inaccuracies in the collection and tabulation of data (SPSS version 12.0, Data Entry; SPSS, Chicago, IL).
The CINHTIA study included a total of 2,024 hypertensive patients with chronic ischemic heart disease. Of these, 0.1% (n =2) had a BMI <20 kg/m2; 17.1% (n = 346) a BMI of 20–24.9 kg/m2; 53.7% (n = 1086) BMI: 25–29.9 kg/m2; 23.7% (n = 480) BMI: 30–34.9 kg/m2; 4.3% (n = 87) BMI: 35–39.9 kg/m2; and 1.1% (n = 23) BMI ≥40 kg/m2. As a result, 29.1% (n = 590) of the study population were obese (BMI ≥30 kg/m2) and 82.8% (n = 1676) were overweight or obese. To better analyze the results, patients were pooled into three groups: BMI: 20–24.9 kg/m2 (n = 346; 17.1%); BMI: 25–29.9 kg/m2 (n = 1086; 53.7%), and BMI ≥30 kg/m2 (n = 590; 29.1%). 50.2% of patients (n = 1016) exhibited abdominal obesity.
Table 1 shows the biodemographic data, cardiovascular risk factors, organ damage, and physical examination and laboratory parameters according to BMI values. The subgroup of patients with BMI ≥30 kg/m2 had a higher proportion of women, diastolic dysfunction, diabetes, dyslipidemia, left ventricular hypertrophy, heart failure, higher systolic and diastolic BP, total cholesterol, LDL-C, triglyceride serum levels and fasting glucose and lower high-density lipoprotein cholesterol values. Very similar results were observed when clinical characteristics were compared according to the presence of abdominal obesity (Table 2).
Table 1. Clinical characteristics of the study population according to the BMI (n = 2,024)
Table 2. Clinical characteristics of the study population according to the presence of abdominal obesity (n = 2,024)
With regard to treatment, although the majority of patients were taking at least four drugs, this proportion was higher in obese subjects. Patients with obesity were taking a similar number of antihypertensive agents, antiplatelets and anticoagulants than the other subgroups, but lipid lowering agents and antidiabetics were more frequently prescribed in the subset of obese patients, P = 0.04 and P < 0.001, respectively (Figure 1).
The different classes of antihypertensive drugs prescribed according to BMI are showed in Figure 2. β-blockers were the most frequent used antihypertensive agent, with no differences according to BMI. Calcium channel blockers (P = 0.006), diuretics (P < 0.001), and angiotensin receptor blockers (P < 0.001) were most commonly prescribed in those with a higher BMI. With regard to treatments, similar trends were observed when comparing patients according to the presence of abdominal obesity.
The BP, LDL-C, and diabetes control rates are shown in Figure 3. There was an inverse relationship between control rates and BMI. The BP was controlled in 51.7% of patients with BMI: 20–24.9 kg/m2, in 42.4% with BMI 25–29.9 kg/m2 and in 29.2% in those with BMI ≥30 kg/m2 (P < 0.001). LDL-C was controlled in 35.2, 30.5, and 27.9%, respectively (P = 0.03). Diabetes control rates were 38.6, 27.6, and 22.2%, respectively (P = 0.023). Those patients with abdominal obesity reported worse BP (33.6% vs. 49.5%, P < 0.001), LDL-C (27.7% vs. 32.0%, P = 0.04) and diabetes (24.0% vs. 36.5%, P = 0.02) control rates.
A multivariate analysis was performed to determine the predictive factors associated with lack of BP, LDL-C, and diabetes controls. As Table 3 shows, abdominal obesity and BMI ≥30 kg/m2 were strong predictors of no BP control.
Table 3. Predictive factors for no cardiovascular risk factors control
The results of our study showed that in a population with hypertension and chronic ischemic heart disease, no differences in age were found according to BMI. However, those with higher BMI had more diabetes, dyslipidemia, left ventricular hypertrophy, heart failure, and worse BP, LDL-C, and fasting diabetes control rates. What did previous studies report about the influence of BMI on clinical profile and cardiovascular outcomes in patients with coronary heart disease?
The Arterial Revascularization Therapies Study trial (13) showed in 1,203 patients who had multivessel coronary artery disease and underwent surgical or percutaneous revascularization between April 1997 and June 1998, that BMI had no effect on 3-year outcome of those who underwent stenting. But those who underwent coronary artery bypass grafting, and were overweight or obese had a significantly better outcome than did those who had a normal BMI with regard to survival. However, it should be noted that, in this study, those with higher BMI were significantly younger. Similar findings have also been reported by others (17,18,26).
In the acute coronary setting, Kosuge et al. (16) analyzed the impact of BMI on outcomes in myocardial infarction between 2001 and 2003. Obese patients were younger and had a higher prevalence of diabetes mellitus, hyperlipidemia, hypertension and smoking. Notably, BMI itself had no impact on in-hospital mortality in these patients treated with primary percutaneous coronary intervention.
Finally, a recent systematic review of over 250,000 patients in 40 cohort studies followed up for 3.8 years reported that overweight and obese patients with coronary heart disease had a lower risk for total and cardiovascular mortality compared with underweight and normal-weight subjects. The better prognosis seen in the overweight and mildly obese groups could not be explained by adjustment for confounding factors. The authors suggested that these findings could be justified by the lack of discriminatory power of BMI to differentiate between body fat and lean mass (27).
How is explained that all these studies suggest that despite obesity undoubtedly increases the risk for developing coronary heart disease, when coronary disease is established, overweight and mild obesity do not seem to adversely affect prognosis?
Indeed, some issues remain unclear. First, although several pathophysiological links between overweight/obesity and many forms of cardiovascular disease have been described, it should be noted that several scientific questions still need to be addressed for a better understanding of the relationship between them (1). Second, the majority of patients included in these studies were in the nineties or in the first years of the present century. This point is very important, because obesity is increasing year by year (28). Previous studies have reported that obese patients with coronary disease were younger, but this trend might be changing (13,16,17,18). What previous data had shown is that obesity promoted early cardiovascular disease and therefore, obese patients were younger. It is likely that this lower age could be the main reason why the prognosis of this subgroup of patients seems to be better. However, because obesity is markedly growing day by day, now these disparities in age according to BMI are disappearing. The data provided from our study showed that the clinical profile in this population is changing and this could translate into a different prognosis. Notably, in our study only 17% of subjects had normal weight and no differences in age were observed between different subgroups according BMI. Unfortunately, because we cannot demonstrate this statement with a cross-sectional study, we consider that further investigations are warranted to confirm this point. Nevertheless, a recent study involving patients with heart failure, another subgroup of patients in which it has been suggested that obesity may be associated with a survival advantage, reported a U-shaped relation between mortality and BMI in the setting of new-onset heart failure after acute coronary syndrome (29).
One important point that supports these findings is the fact that weight loss has been associated with lesser cardiovascular outcomes (30,31). It has been reported that overweight and obese coronary heart disease patients who lost weight markedly improved the cardiovascular risk factors control, including lipids, glucose, and C reactive protein, as well as a trend of lower mortality (30). Furthermore, secondary prevention activities have been associated with a better prognosis and improvement in clinical profile (32,33).
The cross-sectional design of the study was chosen to best represent real-world clinical practice. Consequently, a large population of hypertensive patients with chronic ischemic heart disease was included in the trial with very few patient exclusion criteria. This was achieved by consecutive sampling. This methodology has its limitations because it reduces the level of control that can be exercised to reduce variation and bias (e.g., random sampling and “blind” controls). The large number of patients included in the study, however, and the nature of the endpoints being measured, with no comparators under review, minimizes this theoretical limitation. It is notable that, because this study was performed in Spain, the results may not be generalizable to other countries with different health care delivery.
In conclusion, previous data had shown an obesity paradox in patients with coronary artery disease; however, this may be related with the fact that obese patients who developed ischemic heart disease were younger, and this mask the real prognosis of this population. The results of the present study showed that as BMI increased, the clinical profile worsened as well as the cardiovascular risk factors control. These data suggest that clinical profile in this population is changing and this could translate into a different prognosis. Further investigations are warranted to confirm this statement. Therefore, these data outline the importance of weight reduction in overweight and obese patients with coronary heart disease.