The Metabolic Syndrome in Patients With Heart Failure With Normal Ejection
Presenter: Rajesh K C Vindhya, MD (Columbia University College of Physicians & Surgeons, New York, NY)
Three concepts have emerged recently as possibly essential to understanding important aspects of cardiovascular disease (CVD): phenotype (particularly as it pertains to hypertension), metabolic syndrome (particularly as it pertains to CVD risk), and preserved ejection fraction (particularly for a significant proportion of heart failure patients). Now a study reported at the 2006 Heart Failure Society of America conference has found that among elderly patients with heart failure with preserved ejection fraction, the metabolic syndrome is more often found in those with hypertension than those without hypertension. However, the study found no difference in cardiovascular structure and phenotype between these 2 groups.
The question thus becomes, What is intrinsic to this condition, and what is an incidental aspect of the presentation? How should researchers identify the patients to be studied?
As explained by Rajesh Vindhya, MD: "Obesity, such a common problem in the United States, has been associated with myocardial infarction and coronary artery disease, but it has not been associated with heart failure. So we conducted our research not only with the hope of trying to show an association between obesity and heart failure, but taking the whole metabolic syndrome into account."
The Logic of the Question
Heart failure with normal or preserved ejection fraction, which is subsumed under the umbrella term diastolic heart failure, is unlike true diastolic heart failure, where the problem is intrinsic, Dr. Vindhya explained. In heart failure with preserved ejection fraction, extracardiac factors such as anemia, renal dysfunction, and obesity play a major role. "Since metabolic syndrome is also an extracardiac factor, it makes sense to try and associate it with diastolic heart failure," Dr. Vindhya said.
Subjects with metabolic syndrome have been reported to have higher left ventricular (LV) mass and more concentric LV hypertrophy, as indicated by higher relative wall thickness. This cardiovascular phenotype is often thought to characterize patients with heart failure in the setting of a preserved ejection fraction.
Hypertension is also commonly associated with heart failure with preserved ejection fraction. Dr. Vindhya and his colleagues therefore investigated the presence of the metabolic syndrome in a cohort of subjects with heart failure with preserved ejection fraction who were sorted according to the presence or absence of hypertension and stratified by the presence or absence of the metabolic syndrome.
Subjects
The study involved 71 subjects, all of whom had been diagnosed with heart failure with preserved ejection fraction. Consistent with previous studies, all subjects were required to meet the European Society of Cardiology criteria for diastolic heart failure:
Of the 71 subjects, 46 had clinical hypertension. The 25 patients without hypertension included 4 patients with cardiac amyloid, 7 with hypertrophic cardiomyopathy, 10 with hemochromatosis, and 4 with a restrictive cardiomyopathy. Compared with the hypertensive patients, those without hypertension tended to be older (mean age 71 years vs 44 years), female (80% vs 60% in the hypertensive group), and heavier (mean body mass index [BMI] 32 vs 27 kg/m).
Metabolic Syndrome
Only 8% of the 25 patients without hypertension were identified as having the metabolic syndrome. Among 46 subjects with hypertension, 28 (61%) met criteria for the metabolic syndrome, defined as presence of ≥3 of the following criteria:
There was no difference in age, gender, or race between subjects with or without the metabolic syndrome.
Cardiac Structure and Function/Arterial Properties
In the hypertensive patients, LV volumes and mass were evaluated by freehand 3-dimensional echocardiography, and large conduit artery stiffness was identified by pulse pressure. No differences were seen in cardiac structure, function, or arterial properties between subjects with or without the metabolic syndrome among these hypertensive subjects (Table 1).
Table 1. Cardiac Structure and Function in Hypertensive Subjects
EDV = end-diastolic volume; ESV = end-systolic volume; IVSd = interventricular septum thickness during systole; LV = left ventricular; LVIDd = LV internal diameter during diastole; PWT = posterior wall thickness; RWT =relative wall thickness.
Blood Volume Analysis
Measurements of total blood volume, red cell volume, and plasma volume in a subset of 22 patients (15 with metabolic syndrome and 7 without) were similar in the 2 groups (Table 2).
Table 2. Blood Volume Analysis
BSA = body surface area; BV = blood volume; PV = plasma volume; RCV = red cell volume.
Conclusions
Among the patients with preserved ejection fraction, no significant differences were found between those with and without metabolic syndrome; however, the concomitant prevalence of both conditions is so high that the conclusion of Dr. Vindhya and his colleagues is that further studies are definitely warranted to define the mechanistic interaction of these 2 syndromes.
References
Three concepts have emerged recently as possibly essential to understanding important aspects of cardiovascular disease (CVD): phenotype (particularly as it pertains to hypertension), metabolic syndrome (particularly as it pertains to CVD risk), and preserved ejection fraction (particularly for a significant proportion of heart failure patients). Now a study reported at the 2006 Heart Failure Society of America conference has found that among elderly patients with heart failure with preserved ejection fraction, the metabolic syndrome is more often found in those with hypertension than those without hypertension. However, the study found no difference in cardiovascular structure and phenotype between these 2 groups.
The question thus becomes, What is intrinsic to this condition, and what is an incidental aspect of the presentation? How should researchers identify the patients to be studied?
As explained by Rajesh Vindhya, MD: "Obesity, such a common problem in the United States, has been associated with myocardial infarction and coronary artery disease, but it has not been associated with heart failure. So we conducted our research not only with the hope of trying to show an association between obesity and heart failure, but taking the whole metabolic syndrome into account."
The Logic of the Question
Heart failure with normal or preserved ejection fraction, which is subsumed under the umbrella term diastolic heart failure, is unlike true diastolic heart failure, where the problem is intrinsic, Dr. Vindhya explained. In heart failure with preserved ejection fraction, extracardiac factors such as anemia, renal dysfunction, and obesity play a major role. "Since metabolic syndrome is also an extracardiac factor, it makes sense to try and associate it with diastolic heart failure," Dr. Vindhya said.
Subjects with metabolic syndrome have been reported to have higher left ventricular (LV) mass and more concentric LV hypertrophy, as indicated by higher relative wall thickness. This cardiovascular phenotype is often thought to characterize patients with heart failure in the setting of a preserved ejection fraction.
Hypertension is also commonly associated with heart failure with preserved ejection fraction. Dr. Vindhya and his colleagues therefore investigated the presence of the metabolic syndrome in a cohort of subjects with heart failure with preserved ejection fraction who were sorted according to the presence or absence of hypertension and stratified by the presence or absence of the metabolic syndrome.
Subjects
The study involved 71 subjects, all of whom had been diagnosed with heart failure with preserved ejection fraction. Consistent with previous studies, all subjects were required to meet the European Society of Cardiology criteria for diastolic heart failure:
Signs and symptoms of congestive heart failure;
Normal or at most mildly reduced LV ejection fraction (≥ 45%); and
Evidence of abnormal diastolic function on standard Doppler echocardiographic evaluation of transmitral inflow patterns.
Of the 71 subjects, 46 had clinical hypertension. The 25 patients without hypertension included 4 patients with cardiac amyloid, 7 with hypertrophic cardiomyopathy, 10 with hemochromatosis, and 4 with a restrictive cardiomyopathy. Compared with the hypertensive patients, those without hypertension tended to be older (mean age 71 years vs 44 years), female (80% vs 60% in the hypertensive group), and heavier (mean body mass index [BMI] 32 vs 27 kg/m).
Metabolic Syndrome
Only 8% of the 25 patients without hypertension were identified as having the metabolic syndrome. Among 46 subjects with hypertension, 28 (61%) met criteria for the metabolic syndrome, defined as presence of ≥3 of the following criteria:
Hypertension;
Diabetes mellitus;
Obesity (BMI > 30);
Triglycerides > 150 mg/dL [1.69 mmol/L]); or
HDL-cholesterol < 40 mg/dL (1.04 mmol/L).
There was no difference in age, gender, or race between subjects with or without the metabolic syndrome.
Cardiac Structure and Function/Arterial Properties
In the hypertensive patients, LV volumes and mass were evaluated by freehand 3-dimensional echocardiography, and large conduit artery stiffness was identified by pulse pressure. No differences were seen in cardiac structure, function, or arterial properties between subjects with or without the metabolic syndrome among these hypertensive subjects (Table 1).
Table 1. Cardiac Structure and Function in Hypertensive Subjects
| Parameter | Metabolic Syndrome (n = 28) |
No Metabolic Syndrome (n = 18) |
|---|---|---|
| LV size: | ||
| LVIDd (cm) | 4.6 ± 0.7 | 4.6 ± 0.6 |
| IVSd (cm) | 3.14 ± 0.75 | 3.33 ± 0.4 |
| EDV (mL) | 120 ± 28 | 116 ± 33 |
| ESV (mL) | 56 ± 15 | 56 ± 16 |
| Myocardial characteristics: | ||
| PWT (cm) | 1.3 ± 0.3 | 1.3 ± 0.4 |
| LV mass (g) | 175 ± 37 | 175 ± 59 |
| RWT (cm) | 0.59 ± 0.18 | 0.53 ± 0.16 |
| EDV/mass ratio | 0.70 ± 0.18 | 0.68 ± 0.13 |
| End systolic stress (g/cm) | 115 ± 49 | 146 ± 55 |
| LV function | ||
| Ejection fraction (%) | 53 ± 5 | 52 ± 3 |
| Stroke volume (mL) | 62 ± 16 | 61 ± 18 |
| Arterial properties: | ||
| Pulse pressure (mm Hg) | 58 ± 17 | 64 ± 22 |
| Pulse pressure/stroke volume (mm Hg/mL) | 1.0 ± 0.3 | 1.2 ± 0.6 |
| Arterial elastance (mm Hg/mL) | 1.7 ± 0.4 | 2.1 ± 0.7 |
Measurements of total blood volume, red cell volume, and plasma volume in a subset of 22 patients (15 with metabolic syndrome and 7 without) were similar in the 2 groups (Table 2).
Table 2. Blood Volume Analysis
| Parameter | Metabolic Syndrome (n = 15) |
No Metabolic Syndrome (n = 7) |
|---|---|---|
| BV (cc) | 4630 ± 1000 | 3031 ± 1549 |
| PV (cc) | 3194 ±799 | 3396 ± 1022 |
| RCV (cc) | 1432 ± 244 | 1635 ± 600 |
| BV/BSA (cm/m) | 2388 ± 314 | 2572 ± 574 |
| PV/BSA (cm/m) | 1642 ± 254 | 1734 ± 356 |
| RCV/BSA (cm/m) | 744 ± 97 | 838 ± 262 |
Among the patients with preserved ejection fraction, no significant differences were found between those with and without metabolic syndrome; however, the concomitant prevalence of both conditions is so high that the conclusion of Dr. Vindhya and his colleagues is that further studies are definitely warranted to define the mechanistic interaction of these 2 syndromes.
References
Vindhya RKC, Wajahat R, Titova I, et al. The metabolic syndrome in patients with heart failure with normal ejection fraction. J Cardiac Fail. 2006;12(6 suppl):S20. Abstract 065.
The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005). Eur Heart J. 2005;26:1115-1140.
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