Metabolic Syndrome in Patients with Chronic Heart Failure

Prevalence studies estimate that 23 million people worldwide have HF and two million new cases are diagnosed each year. It is a progressing epidemic problem2-4. Industrialization and urbanization have led the development of chronic non-transmissible diseases4. HF is the common final pathway of most of these diseases that affect the heart5,6. Epidemiological evidence increasingly demonstrates the association between metabolic syndrome (MS) and the presence of cardiovascular abnormalities, since, in an independent manner, risk factors related to HF are the same that make up MS6.


Introduction
Heart failure (HF) is a complex and progressive clinical syndrome that can be defined by structural or functional heart abnormalities, causing insufficient blood pumping for tissue metabolic demand or doing so only by high filling pressures 1 .poor prognosis of the patient, increasing overall mortality by about 1.5 times and cardiovascular mortality by about 2.5 times [9][10][11] .
In 2001, the National Cholesterol Education Program -Adult Treatment Panel III 12 defined the clinical and laboratory criteria for diagnosing MS, which were redefined in 2006 by the International Diabetes Federation (IDF) 13 , with an emphasis on abdominal obesity according to the ethnic group, making the value of waist circumference essential for diagnosis 6 .
The diagnosis of MS can identify the risk for CVD, highlighting the importance of early detection.Knowing the prevalence of MS in the population is necessary for properly planning and directing health actions 14,15 .
This study aimed to evaluate MS in patients with chronic heart failure (CHF) assisted at the Heart Failure Clinic of Hospital Universitário Pedro Ernesto (HUPE).

Methods
This is a cross-sectional descriptive study conducted from April to October 2011, with a convenience sample consisting of HF patients treated at the Heart Failure Clinic of HUPE in the city of Rio de Janeiro.
Inclusion criteria were: patients diagnosed with HF, age > 18 years, of both sexes.The study excluded patients who did not have aby echocardiographic data required for the diagnosis of HF.
The variables were age, sex, skin color, smoking, blood pressure, waist circumference (WC), body mass index [BMI (kg/m²)], blood glucose, HDL, triglycerides and the etiology of HF, functional class according to the New York Heart Association (NYHA) 16 and left ventricular ejection fraction (LVEF).
For assessing blood pressure, the electronic equipment Colin Press-Mate® BP 8800 (Texas, USA) was used.
The anthropometric measurements were taken on a platform-type mechanical scale brand Balmack® (São Paulo, Brazil) with maximum capacity of 150 kg and 100 g precision; in the presence of edema and/or ascites, the dry weight estimated was used 17 .Height was measured by a metal rod stadiometer attached to the scale with precision scale of 0.5 cm; and WC was measured at the midpoint between the iliac crest and the lower costal margin 18 by an inextensible tape.
For diagnosing MS, we used the criteria proposed by IDF 13  The patient using medication to control cholesterol or triglycerides and/or using antihypertensive drugs and/or with previous diagnosis of diabetes mellitus (DM) type 2 was included as positive for the presence of that component of MS as previously defined by the IDF 13 .
To characterize the population, the following was studied: 1) Hypertensive patients: systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg or on drug treatment for HAS 22 ; 2) Diabetic patients: fasting glucose level ≥126 mg/dL, on at least two occasions, or using hypoglycemic drugs 23 ; 3) Dyslipidemic drugs: triglyceride levels ≥150 mg/dL or low-density lipoprotein cholesterol ≥160 mg/dL or HDL cholesterol <40 mg/dL or <50 mg/dL for men and women, respectively, or yet, using hypolipidemic agents 24 .
To determine LVEF as reduced or normal, we used 50% as a cutoff point 25 .
Laboratory data and echocardiographic information were collected from the clinical records.
The study was approved by the Research Ethics Committee from HUPE under no.3049/2011 and all participants signed an Informed Consent Form.
The data were stored in the software Epi Info®, USA, and analyzed in the Statistical Software for Professionals® (STATA) version 10.The continuous variables were expressed as mean±standard deviation and the categorical variables were expressed through proportions.
To analyze the categorical variables, we used the chi-square test (c2) or Fisher's exact test.Continuous variables were tested using the Kolgomorov-Smirnov test to check the normality of distribution.Being normal, they were compared using the Student t test.All statistical analyzes used an alpha error of 5% as a cutoff point for the level of significance.

Results
The study evaluated 90 patients with a mean age of 62.7±12.3years, ranging from 34-85 years, of which 51.0% were males.The clinical and demographic characteristics are detailed in Table 1.
The results showed that MS was present in 71.0%(n=64) of the patients evaluated.The percentage of patients with heart failure is increasing with aging.A greater number of elderly was found in this sample (n=58; 64.4%).
In the classification of patients by BMI range, there was a higher percentage of pre-obesity and obesity (overweight) (n=55; 61.1%), especially among those with MS (n=47; 73.4% ).
Systemic hypertension (SH) and dyslipidemia were the comorbidities mostly found in the population studied [96.7% (n=87) and 61.8% (n=55), respectively].However, when comparing the groups, it was observed that the DM was significantly more frequent in the MS group (p <0.001).
According to the results shown in Figure 1, it can be said that there is a significant relationship between the nutritional diagnosis and the presence of MS.The higher the BMI, the greater the percentage of patients, mostly males (p<0.001).
By comparing the mean values of MS components between the groups with and without syndrome, there was a difference of approximately 12 cm in WC, 6 mmHg in SBP and DBP, 100 mg/dL in triglycerides and 40 mg/dL in blood glucose.HDL values were also lower in the group with MS (Table 2).
There was a growing behavior of average WC, systolic and diastolic blood pressure, triglycerides and fasting glucose values, whereas average HDL values were decreasing according to the number of MS components (Table 3).All individuals evaluated had at least one risk component.

Discussion
The average age found in this study (62.7±2.3 years) is consistent with findings from other national studies 6,26,27 that evaluated HF patients, whose mean age was 61.0 years.Coelho et al. 6 and Balieiro et al. 5 , studying the prevalence of MS in these patients found a mean age of 61.0±13.0 and 57.0±15.0years, respectively.
In this study, it was observed that 51.0% of patients were males, as in the study by Margoto et al. 28 , whose prevalence of males was 51.0% and 54.1%, respectively.The Framingham Heart Study 29 reports that the incidence of HF increases with age and is more common in men.
Barker et al. 30 demonstrated that the increase in HF epidemic occurred in an elderly male population, and the increase in prevalence was directly associated with increased incidence and is therefore directly related to longer survival.
Most patients presented HFREF, which is most common in the elderly.This result contrasts with other studies found in the literature, which says that HFNEF represents 50% of the cases, being more prevalent in the elderly because aging would have a greater impact on ventricular filling than in FEVE 1 .The individuals evaluated presented, with a greater frequency, functional classes I and II, as well as in another study 5 .
Hypertension was, among the risk factors, the most prevalent one (96.7%) in the group, a fact found in other studies 2,23 , although the prevalent etiology was the ischemic one, rather than hypertension.Hypertension is the most important factor of modifiable cardiovascular risk, being associated with HF, with a consequent decrease in survival and worsened quality of life 31 .
The presence of MS showed high frequency in patients with HF, with no difference between the sexes.However, national studies 5,6 have found a MS ratio mainly among women.The major association related to the presence of MS in females may be indirectly correlated to hypertriglyceridemia, obesity, hypertension and high BMI, which are associated with specific characteristics of women after menopause due to hormone disorders 32 .
Meirelles 33 cites several studies showing higher prevalence of MS in women after menopause compared to those in the premenopausal period.This fact may be a direct result from ovarian failure or from metabolic disorders promoted by increased visceral fat secondary to decreased estrogen.It is not clear whether menopause increases cardiovascular risk in all women or only in women with MS 34 .
MS is more prevalent after menopause than in the premenopausal period and may play an important role in CVD.Whereas this study evaluated a large number of elderly women, we emphasize this limitation, since this data has not been analyzed.
Overweight was more frequent among patients with HF.Kenchaiah et al. 35 , in a cohort of 5881 participants, found that for every one-point increase in BMI, there was an increased risk of HF by 5.0% for men and 7.0% for women.Another important finding was the positive association between increased BMI and the number of patients that presented disorders to the MS components.This fact is justified in the literature, since it is true that the increasing incidence of MS is due to the greater number of cases of obesity 36 .
The number of individuals with disorders in the MS components increased by two to three times with aging, being more predominant over 60 years.It is well documented that age contributes to the onset of MS and with the accumulation of metabolic disorders 11 .This correlation between MS and age is described by national studies: Leão et al. 37 found a high prevalence of hypertension and hyperglycemia with increasing behavior with increasing age; and Oliveira et al. 15 found a higher frequency of MS among older individuals.
The prevalence of high blood pressure among individuals with and without MS was similar to the one found in other studies 15,37 .Salaroli et al. 11 also found a higher prevalence of obesity among women, highlighting the close relationship of central obesity with MS.
Hyperglycemia, being six times more frequent in the group with MS, as well as in the study of Leão et al. 37 and 4.5 times in Oliveira et al. 15 , reveals the close relationship between altered glucose metabolism and MS.Fasting glucose is an independent predictor of hospitalization for HF in patients at risk in the presence or absence of prior diagnosis of DM 1 .
Patients with MS and DM have increased cardiovascular morbidity and mortality.The IDF believes that MS is leveraging type 2 DM and CVD 38 .
Individuals with MS had higher average WC, SBP, DBP, triglycerides and blood glucose.Also, those with MS had lower HDL concentrations.The differences among the groups were equally observed in another national study 37 .
Regarding the aggregation of MS components, in this study there was an increase in the average values according to the aggregation of the number of components.
A study 39 evaluating the relative risk of CVD and DM related to the number of components for MS found that the risk of developing CVD is six times higher when four or more components are present.In populations that have presented cardiovascular diseases, secondary prevention becomes even more important.
Therefore, the investigation of MS is a fundamental tool for preventing this, since there is a strong association with cardiovascular mortality.

Conclusion
Individuals with HF presented a high frequency of MS, which is significantly related with excess weight regardless of age.
There was a close relationship between DM and MS, since a significant difference was found between the groups with and without MS.
It is vital to investigate MS for implementing therapeutic actions aimed at reversing MS in cardiac patients, given the association with high mortality in this population.

Figure 1
Figure 1 Nutritional status of the population studied, according to the diagnosis of MS, by sex MS -metabolic syndrome

Chart 1 Diagnostic criteria of metabolic syndrome proposed by the IDF Components IDF
IDF -International Diabetes Federation

Table 1 Clinical and demographic characteristics of the population studied
MS -metabolic syndrome; HF -heart failure; HFREF -heart failure with reduced ejection fraction; HFNEF -heart failure with normal ejection fraction

Table 2 Anthropometric and biochemical variables in the population studied according to the presence of not of metabolic syndrome
MS -metabolic syndrome; WC -waist circumference; SBP -systolic blood pressure; DBP -diastolic blood pressure; TG -triglycerides; HDL -high-density lipoprotein; GLU -glucose; SD -standard deviation.The continuous variables were compared using the Student t test for independent samples.

Table 3 MS components according to the number of risk factors found in the population studied
MS -metabolic syndrome; WC -waist circumference; SBP -systolic blood pressure; DBP -diastolic blood pressure; TG -triglycerides; HDL -high density lipoprotein; GLU -glucose; SD -standard deviation