Skip to main content

Inverse association of long-acting natriuretic peptide with metabolic syndrome in congestive heart failure patients

Abstract

Aims

Long-acting natriuretic peptide (LANP) is one of the peptide hormones in atrial natriuretic peptide (ANP) pro-hormone. Low levels of natriuretic peptide may lead to reduced lipolysis and excessive weight gain in obese patients. The aim of this study was to investigate the relationship between fasting serum LANP level and the metabolic syndrome (MetS) among congestive heart failure (CHF) patients.

Methods

Fasting blood samples were obtained from 186 patients with normal renal function in cardiac clinic outpatients. CHF defined by the American College of Cardiology Foundation and the American Heart Association 2005 Guidelines. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation.

Results

Ninety-eight patients (52.7%) had CHF. There was a tendency of increased fasting LANP levels as the NYHA CHF functional classes increased (p = 0.002). Forty-six of the CHF patients (46.9%) had MetS. Fasting LANP level negatively correlated with MetS among CHF patients (p < 0.001). Univariate linear regression analysis showed that BUN (p = 0.026) positively correlated with fasting serum LANP levels, while body weight (p = 0.009), BMI (p = 0.004), homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.024) and HOMA-β (p = 0.001) negatively correlated with fasting serum LANP levels among the CHF patients. Multivariate forward stepwise linear regression analysis of the significant variables showed that the HOMA-β (R2 change = 0.292, p < 0.001) and HOMA-IR (R2 change = 0.081, p = 0.019) were independent predictors of fasting serum LANP levels in CHF patients.

Conclusions

LANP level is significantly reduced in CHF patients affected by MetS. HOMA-β and HOMA-IR were independent predictors of serum LANP levels in CHF patients.

Introduction

There are four peptide hormones derived from the 126-amino acid atrial natriuretic peptides (ANP) pro-hormone: long-acting natriuretic peptide (LANP; N-terminal pro-ANP 1–30), vessel dilator (N-terminal pro-ANP 31–67), kaliuretic peptide (N-terminal pro-ANP 79–98), and ANP (α-ANP) and these peptide hormones have significant diuretic, natriuretic, and blood-pressure-lowering properties in animals and humans [1]. The biologic effects of the four peptide hormones from ANP pro-hormone include vasodilation mediated via enhancing guanylate cyclase activity, with a resultant increase in the intracellular messenger cyclic guanosine monophosphate (cGMP), and inhibit the vasoconstrictive peptide endothelin [2]. ANP also activates cGMP-dependent protein kinase, leading to perilipin and hormone-sensitive lipase phosphorylation, and induces lipolysis [3]. ANP is rapidly cleared from the circulation with a half-life of 3–4 minutes. No receptors for N-terminal pro-ANP are known today; therefore this peptide circulates longer which leads to significant higher concentrations in blood compared to ANP. Thus, circulating levels of N-terminal pro-ANP are less sensitive to the pulsatile secretion of ANP and may better reflect chronic levels of ANP secretion than the rapidly fluctuating levels of ANP [1, 2].

The metabolic syndrome (MetS) is associated with increased cardiovascular events [4]. The prevalence of MetS among congestive heart failure (CHF) patients was more than double compared with that in the general population in Japan [5]. A recent study noted that MetS predicted CHF independent of interim myocardial infarction and prevalent diabetes in elderly Finns during a 20-year follow-up [6]. CHF was also associated with insulin resistance independent of diabetes mellitus in a large community-based sample of elderly men [7]. It can be speculated that low levels of natriuretic peptide may lead to reduced lipolysis and excessive weight gain in obese patients, which may be one of the biological alterations that contribute to the development of obesity [8]. Lower plasma N-terminal pro-ANP levels were also associated with the development of insulin resistance (HOMA-IR) and MetS [9]. LANP is one of the N-terminal pro-ANP. There is no study about the association between serum LANP levels and MetS in CHF patients. The aim of this study was to investigate the relationship between fasting serum LANP level and the MetS among CHF patients.

Material and methods

Patients

Between October 2009 and December 2009, 186 consecutive clinic outpatients in a medical center in Hualien, eastern Taiwan (80 males and 106 females, age range 37–88 years) were enrolled into this study. The Protection of the Human Subjects Institutional Review Board of Tzu-Chi University and Hospital approved this study. Patients were excluded if they had any acute infection, acute myocardial infarction, pulmonary edema, liver cirrhosis, thyroid disease, chronic renal failure (serum creatinine ≥1.2 mg/dl) at the time of blood sampling or if they refused to provide informed consent for the study.

Definition of CHF

In the present study, we included patients with stages C/D CHF defined by the American College of Cardiology Foundation and the American Heart Association 2005 Guidelines. Heart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood [10]. New York Heart Association (NYHA) CHF functional classes were collected from the medical records. According to the European Society of Cardiology 2007 Guidelines, we further divided them into 2 groups: heart failure with preserved ejection fraction (HFPEF; LV ejection fraction (EF) ≥50%) and heart failure with reduced ejection fraction (HFREF; LVEF <50%) [11].

Anthropometric analysis

Body weight was measured to the nearest half-kilogram with the patient in light clothing and without shoes. Height was measured to the nearest half centimeter. Waist circumference was measured in a horizontal plane, midway between the inferior margin of the ribs and the superior border of the iliac crest. Body mass index (BMI) was calculated as weight (kilograms) divided by height squared (meters). Bioimpedance measurements of fat mass were performed at the bedside according to the standard, tetrapolar, whole body (hand-foot) technique, using a single-frequency (50-kHz) analyzer (Biodynamic-450, Biodynamics Corporation, Seattle, MA, USA). Measurements were carried out by the same operator; fat mass was collected and analyzed by specific formulas provided by the manufacturer [1215].

Biochemical investigations

Fasting blood samples of approximately 0.5 ml for measuring complete blood count (Sysmex K-1000, Bohemia, NY, USA) and other factors were immediately centrifuged at 3000 g for 10 min. Serum levels of blood urea nitrogen (BUN), creatinine (Cre), fasting glucose, total cholesterol (TCH), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-cholesterol), low-density lipoprotein-cholesterol (LDL-cholesterol), albumin, globulin, and C-reactive protein (CRP) were measured using an autoanalyzer (COBAS Integra 800, Roche Diagnostics, Basel, Switzerland). Serum LANP (N-terminal pro-ANP 1–30 or pre-pro-ANP 26–55, Phoenix Pharmaceuticals Inc., Burlingame, CA, USA) levels were measured using a commercial available enzyme immunoassay kit (EIA). The limit of detection calculated as the concentration of human LANP corresponding to the blank average minus three standard deviations was 0.1 ng/ml. The inter- and intra-assay coefficients of variation for LANP were 6.2% and 5.4%, respectively [12]. Serum insulin levels were measured using the MEIA (microparticle enzyme immunosobent assay) method by an autoanalyzer (Abbott Laboratories, Abbott Park, IL, USA). Insulin resistance was evaluated using a homeostasis model assessment of insulin resistance (HOMA-IR) as follows: HOMA-IR = fasting plasma glucose (mg/dl) × fasting serum insulin (μU/ml)/405 [15]. HOMA-β (pancreatic β-cell function) was calculated using the following formula: HOMA-β = fasting serum insulin (μU/ml) × 360/fasting plasma glucose (mg/dl) − 63 [16].

Metabolic syndrome and its components

The prevalence of MetS was defined using the International Diabetes Federation definition [17]. People were classified as having MetS if they had central (abdominal) obesity with a waist circumference ≥90 cm (men) or ≥80 cm (women) (Chinese criteria), and were matching two or more of the following criteria: fasting serum glucose of 110 mg/dl or more, triglycerides of 150 mg/dl or higher, HDL-cholesterol level less than 40 mg/dl in men or less than 50 mg/dl in women, or blood pressure of 130/85 mmHg or higher. The use of antihypertensive medication was considered as high blood pressure in this analysis. Type 2 diabetes was determined according to World Health Organization criteria [18]. A person was regarded as diabetic if the fasting plasma glucose was either 126 mg/dl or more, or if the 2 h glucose during an oral glucose tolerance test was 200 mg/dl or more, or if he/she was using diabetes medication (oral or insulin).

Statistical analysis

Data are expressed as means ± standard deviation (SD) and were tested for normal distribution by Kolmogorov-Smirnov statistics. Categorical variables were analyzed by the Chi-square test. Comparisons between patients were performed using Student’s independent t test (two-tailed) for the normally distributed data or the Mann–Whitney U test for the parameters that presented with non-normal distribution (fasting glucose, CRP, LANP). The significance of differences of LANP between groups (NYHA functional CHF classes) was analyzed by the Kruskal-Wallis analysis of variance (AVONA) test. Clinical variables that correlated with serum LANP levels in CHF patients were evaluated by univariate linear regression analyses. Variables that were significantly associated with LANP in CHF patients were tested for independency in multivariate forward stepwise regression analysis. Data were analyzed using SPSS for Windows (version 13.0; SPSS Inc., Chicago, IL, USA). A p-value < 0.05 was considered statistically significant.

Results

The clinical characteristics of the patients with or without CHF are presented in Table 1. Ninety-eight patients (52.7%) had CHF (64 dilated cardiomyopathy, 24 ischemic heart diseases and 10 valvular heart diseases). CHF patients had older age (p = 0.037) and higher LANP level (p = 0.035) than patients without CHF. There was no difference of the fasting serum LANP levels (p = 0.090) between HFREF patients (n = 24; 4.82 ± 3.37 ng/ml) and HFPEF patients (n = 74; 3.03 ± 2.84 ng/ml). However, there was a tendency toward increased fasting LANP levels as the NYHA CHF functional classes increased in CHF patients (p = 0.002; Figure 1). The highest value of the fasting LANP level was noted with NYHA CHF functional class IV (11.57 ± 1.68 ng/ml) and the lowest value of the fasting LANP level was noted with NYHA CHF functional class I (0.97 ± 0.61 ng/ml). Although, there is a tendency of lower serum LANP levels in patients with MetS than without MetS according the various CHF classes (I-IV). LANP levels in patients with MetS than without MetS did not differ statistically according the various CHF classes (Table 2).

Table 1 Clinical variables of the patients with or without congestive heart failure
Figure 1
figure1

Fasting serum long-acting natriuretic peptide levels in New York Heart Association functional classes among the 98 congestive heart failure patients. Data was analyzed by the Kruskal-Wallis analysis of variance (AVONA) test.

Table 2 Serum long-acting natriuretic peptide levels in the various congestive heart failure classes (I-IV) in patients with and without metabolic syndrome

The clinical characteristics and fasting serum LANP levels of the CHF patients are presented in Table 3. Forty-six CHF patients (46.9%) had MetS, whereas the remaining 52 patients (53.1%) did not. CHF patients who had MetS had lower serum fasting LANP levels than those without MetS (p < 0.001). LANP levels did not differ statistically by gender distribution, diabetes, hypertension, hyperlipidemia, ARB, ACEI, CCB, β-blocker, thiazide, statin, fibrate, sulfaurea, metformin, aspirin, or clopidogrel drugs used.

Table 3 Clinical characteristics and fasting serum long-acting natriuretic peptide levels of 98 congestive heart failure patients

The univariate linear analysis of fasting serum LANP levels in CHF patients is presented in Table 4. BUN (r = 0.317; p = 0.026) positively correlated with fasting serum LANP levels, while body weight (r = −0.370; p = 0.009), BMI (r = −0.407; p = 0.004), HOMA-IR (r = −0.321; p = 0.024) and HOMA-β (r = −0.469; p = 0.001) negatively correlated with fasting serum LANP levels among the CHF patients.

Table 4 Correlation of fasting serum long-acting natriuretic peptide levels and clinical variables by univariate linear regression analyses among the 98 congestive heart failure patients

Multivariate forward stepwise linear regression analysis of the variables that were significantly associated with fasting serum LANP levels among CHF patients showed that HOMA-β (β = −0.486, R2 change = 0.292, p < 0.001) and HOMA-IR (β = −0.289, R2 change = 0.081, p = 0.019) were the independent predictors of fasting serum LANP levels (Table 5).

Table 5 Multivariate stepwise linear regression analysis of body weight, body mass index, blood urea nitrogen, HOMA-IR and HOMA-β: correlation to fasting serum long-acting natriuretic peptide among 98 congestive heart failure patients

Discussion

The results of our study showed that the fasting LANP level was negatively associated with MetS in CHF patients. Pancreatic beta cell function and insulin resistance were independent predictors of the serum LANP level among CHF patients.

Cardiac natriuretic peptides consist of a family of six peptide hormones that are synthesized by three separate genes and then stored as three separate pro-hormones (i.e. 126-amino acid atrial natriuretic peptide (ANP), 108-amino acid B-type natriuretic peptide (BNP) and 103-amino acid C-type natriuretic peptide (CNP) pro-hormones). The ANP pro-hormone contains four peptide hormones: LANP, vessel dilator, kaliuretic peptide and ANP [1]. Cardiac natriuretic peptides are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis [19]. High plasma level of LANP was detected in CHF patients and increased in patients of NYHA CHF functional classes II and III [20]. Our study also noted CHF patients had higher LANP levels and noted a tendency for increasing fasting LANP levels as the NYHA CHF functional classes increased in CHF patients. The highest value of the fasting LANP level was noted in NYHA CHF functional class IV, and the lowest value was noted in NYHA CHF functional class I.

MetS represents a constellation of hypertension, abdominal obesity, impaired fasting glucose, and dyslipidaemia, and it has been shown to be a risk factor for cardiovascular disease [17]. CHF is associated with insulin resistance independent of diabetes mellitus, and the prevalence of MetS is high in CHF patients [5, 7, 21]. It is conceivable that the increased prevalence of MetS in CHF patients is both the cause and the result of CHF, as activation of both the sympathetic nervous system and rennin-angiotensin system causes the metabolic components [22]. Recent study noted that MetS predicted CHF independent of interim myocardial infarction and prevalent diabetes in elderly Finns, and MetS increases mortality in CHF patients [6, 21]. Natriuretic peptides induce natriuresis and diuresis, reduce blood pressure, and, moreover, have powerful lipolytic and lipomobilizing activity in humans [23]. At least two adipocyte lipases are important for controlling lipolysis, hormone-sensitive lipase and adipocyte triglyceride lipase. Perilipin and possibly other proteins of the lipid droplet surface are master regulators of lipolysis, protecting or exposing the triglyceride core of the droplet to lipases [24]. ANP increases the intracellular cyclic guanosine monophosphate (cGMP) concentration, which activates cGMP-dependent protein kinase, leading to perilipin and hormone-sensitive lipase phosphorylation, and induces lipolysis [3, 25]. Lower plasma N-terminal proatrial natriuretic peptide levels were associated with the development of MetS [9]. ANP increases the production of adiponectin by human adipocytes, as well as in patients with CHF [26]. Serum adiponectin values were found to correlate inversely with the presence of MetS [14, 15]. Our study also noted that CHF patients with MetS had lower fasting serum LANP levels.

Human studies indicated that ANP is removed by the lung, kidney, and liver and degraded by natriuretic peptide receptor-C (NPRC), neprilysin, and insulin-degrading enzyme [27]. The reduced glomerular filtration rate may contribute to raise ANP levels through a reduced renal clearance of the peptides [28]. Our study found that BUN positively correlated with fasting serum LANP levels among the CHF patients. Obese individuals in the cohorts of the Framingham Heart Study were found to have lower plasma N-terminal pro-atrial natriuretic peptide levels than those with normal weight [29]. N-terminal pro-atrial natriuretic peptide was also inversely correlated with BMI in a survey of adult male population from Southern Italy [30]. Our study also found that body weight and BMI negatively correlated with fasting serum LANP levels among CHF patients. ANP increased in pancreatic β-cell death was observed in ANP-treated BRIN-BD11 β-cells [31]. Long-term treatment with ANP inhibited ATP production and insulin secretion in rat pancreatic islets [32]. Lower plasma N-terminal pro-ANP levels were associated with the development of insulin resistance in humans [9]. Our study also showed that HOMA-IR, and HOMA-β negatively correlated with fasting serum LANP levels among CHF patients. The multivariate forward stepwise linear regression analysis of the significant variables showed that HOMA-β and HOMA-IR were the independent predictors of fasting serum LANP levels in our study.

Our study noted low levels of LANP in CHF patients may lead to decreased lipolysis and this may be linked to the development of MetS and noted a tendency for increasing fasting LANP levels as the NYHA CHF functional classes increased in CHF patients. Our study also found that BMI negatively correlated with fasting serum LANP levels among CHF patients. MetS is associated with increased cardiovascular events [4]. Numerous studies have documented an obesity paradox, in which overweight and obese people with CHF have a better prognosis than patients who are not overweight or obese [3335]. The reasons for the obesity paradox in CHF remain unclear. The complex constellation of physical, metabolic, neuronal, and hormonal alterations in obesity may lead to structural and functional alterations in the heart [33]. There is a need for prospective studies to elucidate mechanisms for this relationship.

Many factors may affect serum LANP levels, such as drugs, clearance of LANP, and associated diseases. Type 2 DM is a heterogeneous disorder with a complex aetiology that develops in response to genetic and environment influences. The pathophysiology of type 2 DM is characterized by impaired insulin secretion, peripheral insulin resistance and excessive hepatic glucose production [18]. Although our study noted LANP level was significantly negatively related to the pancreatic beta cell function and insulin resistance in CHF patients. However, LANP levels did not differ statistically by diabetes in this study. Many factors such as excessive hepatic glucose production, case numbers, and drugs may affect the result. Pharmacological interventions have been shown to influence serum ANP in humans. Beta-receptor antagonists appear to augment plasma ANP and cGMP concentrations [36]. Initiation of atorvastatin in the early phase of an acute myocardial infarction has beneficial effects on decreasing ANP level after 24 weeks treatment [37]. Pioglitazone does not alter the circulating levels of ANP in type II diabetes mellitus patients [38]. Our results did not show a relationship between statins or peroxisome proliferator-activated receptor γ agonists or other drugs (angiotensin receptor blocker, angiotensin-converting enzyme inhibitor, calcium channel blocker, or thiazide diuretic) and serum LANP among CHF patients. Further studies are required to elucidate the relationship between medication and LANP in CHF patients.

Our study has some limitations. Firstly, this study was of cross-sectional design. Therefore, our findings should be investigated in long-term prospective studies before a causal relationship between serum LANP and MetS in CHF patients can be established. Secondly, most studies have focused on ANP effects on lipolysis and adipose tissue. However, lack of LANP effects has been investigated. Thirdly, other N-terminal ANP pro-hormone peptides such as vessel dilator or kaliuretic peptide have the same effects as LANP also needed further investigated. Further studies are needed to show the N-terminal ANP pro-hormone peptides effects on MetS in CHF patients.

Conclusion

The present study shows there was a tendency of increased fasting LANP levels as the NYHA CHF functional classes increased and a negative association between circulating fasting LANP and MetS among CHF patients. HOMA-β and HOMA-IR were independent predictors of the serum LANP level among the CHF patients. LANP level was significantly negatively related to the pancreatic beta cell function and insulin resistance in these patients.

Abbreviations

ANP:

atrial natriuretic peptide

BUN:

blood urea nitrogen

CHF:

congestive heart failure

cGMP:

cyclic guanosine monophosphate

Cre:

creatinine

CRP:

C-reactive protein

HDL-C:

high-density lipoprotein-cholesterol

HFPEF:

heart failure with preserved ejection fraction

HFREF:

and heart failure with reduced ejection fraction

HOMA-IR:

homeostasis model assessment of insulin resistance

HOMA-β:

homeostasis model assessment of beta cell function

LANP:

long-acting natriuretic peptide

LDL-C:

low-density lipoprotein-cholesterol

MetS:

metabolic syndrome

NPRC:

natriuretic peptide receptor-C

TCH:

total cholesterol

TG:

triglyceride.

References

  1. 1.

    Vesely DL: Which of the cardiac natriuretic peptides is most effective for the treatment of congestive heart failure, renal failure and cancer?. Clin Exp Pharmacol Physiol. 2006, 33: 169-176. 10.1111/j.1440-1681.2006.04344.x.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Vesely DL: Atrial natriuretic peptides: anticancer agents. J Investig Med. 2005, 53: 360-365.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Lafontan M, Moro C, Sengenes C, Galitzky J, Crampes F, Berlan M: An unsuspected metabolic role for atrial natriuretic peptides: the control of lipolysis, lipid mobilization, and systemic nonesterified fatty acids levels in humans. Arterioscler Thromb Vasc Biol. 2005, 25: 2032-2042. 10.1161/01.ATV.0000183728.14712.d8.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Wilson PW, D'Agostino RB, Parise H, Sullivan L, Meigs JB: Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation. 2005, 112: 3066-3072. 10.1161/CIRCULATIONAHA.105.539528.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Miura Y, Fukumoto Y, Shiba N, Miura T, Shimada K, Iwama Y: Prevalence and clinical implication of metabolic syndrome in chronic heart failure. Circ J. 2010, 74: 2612-2621. 10.1253/circj.CJ-10-0677.

    Article  PubMed  Google Scholar 

  6. 6.

    Wang J, Sarnola K, Ruotsalainen S, Moilanen L, Lepistö P, Laakso M: The metabolic syndrome predicts incident congestive heart failure: a 20-year follow-up study of elderly Finns. Atherosclerosis. 2010, 210: 237-242. 10.1016/j.atherosclerosis.2009.10.042.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Ingelsson E, Sundström J, Arnlöv J, Zethelius B, Lind L: Insulin resistance and risk of congestive heart failure. JAMA. 2005, 294: 334-341. 10.1001/jama.294.3.334.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Beleigoli AM, Diniz MF, Ribeiro AL: Natriuretic peptides: linking heart and adipose tissue in obesity and related conditions-a systematic review. Obes Rev. 2009, 10: 617-626. 10.1111/j.1467-789X.2009.00624.x.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Wang TJ, Larson MG, Keyes MJ, Levy D, Benjamin EJ, Vasan RS: Association of plasma natriuretic peptide levels with metabolic risk factors in ambulatory individuals. Circulation. 2007, 115: 1345-1353. 10.1161/CIRCULATIONAHA.106.655142.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG: 2009 focused update incorporated into the ACC/AHA, Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2005, 2009 (119): e391-e479.

    Google Scholar 

  11. 11.

    Paulus WJ, Tschöpe C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE: How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007, 28: 2539-2550. 10.1093/eurheartj/ehm037.

    Article  PubMed  Google Scholar 

  12. 12.

    Hsu BG, Shih MH, Yang YC, Ho GJ, Lee MC: Fasting long-acting natriuretic peptide correlates inversely with metabolic syndrome in kidney transplantation patients. Transplant Proc. 2012, 44: 646-650. 10.1016/j.transproceed.2011.11.008.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Hsu BG, Chen YC, Lee RP, Lee CC, Lee CJ, Wang JH: Fasting serum level of fatty-acid-binding protein 4 positively correlates with metabolic syndrome in patients with coronary artery disease. Circ J. 2010, 74: 327-331. 10.1253/circj.CJ-09-0568.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Wang JH, Lee CJ, Lee CC, Chen YC, Lee RP, Hsu BG: Fasting adiponectin is inversely correlated with metabolic syndrome in patients with coronary artery disease. Intern Med. 2010, 49: 739-747. 10.2169/internalmedicine.49.3093.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Tsai JP, Liou HH, Liu HM, Lee CJ, Lee RP, Hsu BG: Fasting serum fatty acid-binding protein 4 level positively correlates with metabolic syndrome in hemodialysis patients. Arch Med Res. 2010, 41: 536-540. 10.1016/j.arcmed.2010.09.007.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Narumi H, Yoshida K, Hashimoto N, Umehara I, Funabashi N, Yoshida S: Increased subcutaneous fat accumulation has a protective role against subclinical atherosclerosis in asymptomatic subjects undergoing general health screening. Int J Cardiol. 2009, 135: 150-155. 10.1016/j.ijcard.2008.03.044.

    Article  PubMed  Google Scholar 

  17. 17.

    Alberti KG, Zimmet PZ, Shaw J: Metabolic syndrome-a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med. 2006, 23: 469-480.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Alberti KG, Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications. I. Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998, 15: 539-553. 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Clerico A, Recchia FA, Passino C, Emdin M: Cardiac endocrine function is an essential component of the homeostatic regulation network: physiological and clinical implications. Am J Physiol Heart Circ Physiol. 2006, 290: H17-H29.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Azizi C, Maistre G, Kalotka H, Isnard R, Barthélemy C, Masson F: Plasma levels and molecular forms of proatrial natriuretic peptides in healthy subjects and in patients with congestive heart failure. J Endocrinol. 1996, 148: 51-57. 10.1677/joe.0.1480051.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Tamariz L, Hassan B, Palacio A, Arcement L, Horswell R, Hebert K: Metabolic syndrome increases mortality in heart failure. Clin Cardiol. 2009, 32: 327-331. 10.1002/clc.20496.

    Article  PubMed  Google Scholar 

  22. 22.

    Wang S, Soni KG, Semache M, Casavant S, Fortier M, Pan L: Renin-angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: an integrated view in humans. J Hypertens. 2008, 26: 831-843. 10.1097/HJH.0b013e3282f624a0.

    Article  Google Scholar 

  23. 23.

    Lafontan M, Moro C, Berlan M, Crampes F, Sengenes C, Galitzky J: Control of lipolysis by natriuretic peptides and cyclic GMP. Trends Endocrinol Metab. 2008, 19: 130-137. 10.1016/j.tem.2007.11.006.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Wang S, Soni KG, Semache M, Casavant S, Fortier M, Pan L: Lipolysis and the integrated physiology of lipid energy metabolism. Mol Genet Metab. 2008, 95: 117-126. 10.1016/j.ymgme.2008.06.012.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Savoia C, Volpe M, Alonzo A, Rossi C, Rubattu S: Natriuretic peptides and cardiovascular damage in the metabolic syndrome: molecular mechanisms and clinical implications. Clin Sci. 2009, 118: 231-240. 10.1042/CS20090204.

    Article  PubMed  Google Scholar 

  26. 26.

    Tsukamoto O, Fujita M, Kato M, Yamazaki S, Asano Y, Ogai A: Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure. J Am Coll Cardiol. 2009, 53: 2070-2077. 10.1016/j.jacc.2009.02.038.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Potter LR: Natriuretic peptide metabolism, clearance and degradation. FEBS J. 2011, 278: 1808-1817. 10.1111/j.1742-4658.2011.08082.x.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  28. 28.

    Charloux A, Brandenberger G, Piquard F, Geny B: Dysregulation of pulsatility in aging IV. Pulsatile signaling and cardiovascular aging: functions and regulation of natriuretic peptide signaling. Ageing Res Rev. 2008, 7: 151-163. 10.1016/j.arr.2007.12.001.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson PW: Impact of obesity on plasma natriuretic peptide levels. Circulation. 2004, 109: 594-600. 10.1161/01.CIR.0000112582.16683.EA.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Rubattu S, Barbato A, Marchitti S, Iacone R, Di Castro S, Evangelista A: Determinants of N-terminal proatrial natriuretic peptide plasma levels in a survey of adult male population from Southern Italy. J Hypertens. 2010, 28: 1638-1645. 10.1097/HJH.0b013e32833a39aa.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Russell MA, Morgan N: Expression and functional roles of guanylate cyclase isoforms in BRIN-BD11 β-cells. Islets. 2010, 2: 23-31.

    Article  Google Scholar 

  32. 32.

    You H, Laychock SG: Long-term treatment with atrial natriuretic peptide inhibits ATP production and insulin secretion in rat pancreatic islets. Am J Physiol Endocrinol Metab. 2011, 300: E435-E444. 10.1152/ajpendo.00398.2010.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Abel ED, Litwin SE, Sweeney G: Cardiac remodeling in obesity. Physiol Rev. 2008, 88: 389-419. 10.1152/physrev.00017.2007.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  34. 34.

    Lavie CJ, Milani RV, Ventura HO, Romero-Corral A: Body composition and heart failure prevalence and prognosis: getting to the fat of the matter in the "obesity paradox". Mayo Clin Proc. 2010, 85: 605-608. 10.4065/mcp.2010.0333.

    PubMed Central  Article  PubMed  Google Scholar 

  35. 35.

    Gaddam KK, Ventura HO, Lavie CJ: Metabolic syndrome and heart failure-the risk, paradox, and treatment. Curr Hypertens Rep. 2011, 13: 142-148. 10.1007/s11906-011-0179-x.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Luchner A, Burnett JC, Jougasaki M, Hense HW, Riegger GA, Schunkert H: Augmentation of the cardiac natriuretic peptides by beta-receptor antagonism: evidence from a population-based study. J Am Coll Cardiol. 1998, 32: 1839-1844. 10.1016/S0735-1097(98)00478-1.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Teshima Y, Yufu K, Akioka H, Iwao T, Anan F, Nakagawa M: Early atorvastatin therapy improves cardiac function in patients with acute myocardial infarction. J Cardiol. 2009, 53: 58-64. 10.1016/j.jjcc.2008.08.008.

    Article  PubMed  Google Scholar 

  38. 38.

    de Boer RA, Martens FM, Kuipers I, Boomsma F, Visseren FL: The effects of the PPAR-gamma agonist pioglitazone on plasma concentrations of circulating vasoactive factors in type II diabetes mellitus. J Hum Hypertens. 2010, 24: 74-76. 10.1038/jhh.2009.84.

    CAS  Article  PubMed  Google Scholar 

Download references

AcknAcknowledgements

This study was supported by grants from Buddhist Tzu Chi Hospital (TCRD 98–32 and TCRD 100–02) in Taiwan.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Bang-Gee Hsu.

Additional information

Competing interests

All authors declare that they have no conflict of interest.

Authors’ contributions

Lee CJ researched and analyzed data. Wang JH and Hsu BG designed of the study, interpretation of data and wrote the manuscript. Hsieh JC, Chen YC and Wang JH collected the data. All authors read and approved the final version of the manuscript.

Authors’ original submitted files for images

Below are the links to the authors’ original submitted files for images.

Authors’ original file for figure 1

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wang, J., Lee, C., Hsieh, J. et al. Inverse association of long-acting natriuretic peptide with metabolic syndrome in congestive heart failure patients. Diabetol Metab Syndr 5, 19 (2013). https://doi.org/10.1186/1758-5996-5-19

Download citation

Keywords

  • Long-acting natriuretic peptide
  • Congestive heart failure
  • Metabolic syndrome
  • Homeostasis model assessment of insulin resistance