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Original Investigation |

Circulating Adiponectin Levels and Mortality in Elderly Men With and Without Cardiovascular Disease and Heart Failure FREE

S. Goya Wannamethee, PhD; Peter H. Whincup, FRCP; Lucy Lennon, MSc; Naveed Sattar, MD
[+] Author Affiliations

Author Affiliations: Department of Primary Care and Population Sciences, Royal Free and University College Medical School (Dr Wannamethee and Ms Lennon), and Division of Community Health Sciences, St George’s, University of London (Dr Whincup), London, England; and Department of Vascular Biochemistry, University of Glasgow, Glasgow, Scotland (Dr Sattar).


Arch Intern Med. 2007;167(14):1510-1517. doi:10.1001/archinte.167.14.1510.
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Published online

Background  High adiponectin levels have been associated with reduced cardiovascular risk but have been shown to predict mortality in those at high risk for vascular disease. We examined the relationship between adiponectin levels and mortality in older men with and without diagnosed cardiovascular disease (CVD) and heart failure.

Methods  Prospective study of 4046 men aged 60 to 79 years drawn from general practices in 24 British towns and followed up for a mean of 6 years, during which 734 deaths occurred. The men were divided into the following groups according to the presence of physician-diagnosed CVD and heart failure: (1) those with no CVD or heart failure; (2) those with CVD but without heart failure; and (3) those with heart failure (with or without CVD).

Results  After adjustment for a wide range of baseline characteristics, adiponectin levels were positively associated with significantly increased all-cause and CVD mortality in men with no diagnosed CVD or heart failure (top third vs bottom third adjusted relative risk, 1.55 [95% confidence interval (CI), 1.19-2.02; P = .002 for trend] vs 1.53 [95% CI, 1.03-2.27; P = .02 for trend]), as well as in men with diagnosed heart failure ([adjusted relative risk, 2.37 [95% CI, 0.64-8.79; P = .04 for trend] vs 3.43 [95% CI, 0.54-21.70; P = .008 for trend]). No association was seen in those with diagnosed CVD without heart failure. Adjustment for weight loss and renal function made minor differences to these relationships.

Conclusions  In older men, high adiponectin levels are associated with increased all-cause and CVD mortality in those with heart failure and those free of CVD. Such observations suggest that adiponectin levels may reflect a balance of both protective and harmful factors.

Figures in this Article

Levels of adiponectin, in contrast to other adipokines, are reduced in obese patients and in those with type 2 diabetes mellitus. Adiponectin has been proposed to have insulin-sensitizing, anti-inflammatory, and antiatherogenic properties.13 High levels of circulating adiponectin have been associated with reduced risks of cardiovascular disease (CVD) in some population studies,48 although some,911 including a recent nested case-control study from our group in the original British Regional Heart Study,11 have shown no association or a weak one. However, in recent prospective studies, high levels of plasma adiponectin were shown to be a predictor of mortality in patients with chronic heart failure,12,13 in patients presenting with coronary artery disease,14,15 in patients with chronic kidney disease,16 and most recently in older community-dwelling men and women.17 These conflicting findings raise the possibilities that adiponectin may have different prognostic implications in older subjects or in populations at high risk of vascular disease. Furthermore, despite the increase in visceral fat and insulin resistance with normal aging,18,19 adiponectin levels are known to increase with age.20 It has been recently suggested that the age-related decline of renal function results in a reduction in renal adiponectin clearance and may contribute to the increase in adiponectin levels in the elderly.20 However, little is known about the association between adiponectin levels and mortality in the general older population or its relation to declining renal function, which is itself associated with increased mortality in this group.21 We have therefore examined the relationship between adiponectin levels and all-cause mortality in elderly men (aged 60-79 years). We did so separately in those with and without diagnosed CVD (including coronary heart disease or stroke) and in those with diagnosed heart failure (including those with and without CVD). Our aim was to determine whether adiponectin levels were associated with increased CVD mortality in only those with existing vascular disease or heart failure or whether this extended to all individuals.

The British Regional Heart Study is a prospective study of CVD involving 7735 men aged 40 to 59 years selected from the age and sex registers of a general practice in each of 24 British towns, who were screened during the period between January 1, 1978, and June 30, 1980.22 From February 1, 1998, to March 31, 2000, all surviving men (n = 5547), now aged 60 to 79 years, were invited for a follow-up examination after a 20-year interval. Ethics approval was provided by all relevant local research ethics committees. All men provided informed written consent to the investigation, which was carried out in accordance with the Declaration of Helsinki. All men completed a questionnaire at reexamination, providing details of their medical history and lifestyle behaviors. The men were asked to fast for a minimum of 6 hours, during which they were instructed to drink only water, and to attend for measurements at a specified time between 8 AM and 6 PM. A fasting blood sample was collected using a commercially available system (Sarstedt Monovette; Sarstedt, Numbrecht, Germany), and samples were stored at −70°C for subsequent analyses; 4252 men (76.7% of survivors) attended for examination. The samples were stored at −20°C on the day of collection and transferred in batches for storage at −70°C until analysis, performed after no more than 1 freeze-thaw cycle. Twelve-lead electrocardiography was performed using a commercially available recorder (Sicard 460; Siemens, Erlangen, Germany).

CVD RISK FACTORS

Details of measurement and classification methods for smoking status; physical activity; body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared); social class; alcohol intake; blood pressure; levels of blood lipids, blood glucose, and insulin; and measures of lung function (forced expiratory volume in 1 second) in this cohort have been described previously.2226 The men were also asked whether they had lost weight in the 3 years prior to the 1998-2000 reexamination and whether the weight loss was intentional or unintentional. Blood pressure measured using an automated blood pressure monitor (Dinamap 1846; Critikon Services, Berkshire, England) was adjusted for observer variation.27 Blood glucose and insulin concentrations were adjusted for the effects of fasting duration and time of day.26 Insulin resistance was estimated according to the homeostasis model assessment (the product of the fasting glucose level [in milligrams per deciliter] and the insulin level [in micro–international units per milliliter] divided by the constant 405).28 (To convert fasting glucose level to millimoles per liter, multiply milligrams per deciliter by 0.0555; to convert insulin level to picomoles per liter, multiply micro–international units per milliliter by 6.945.) Prevalent diabetes included men with a diagnosis of diabetes or men with a fasting blood glucose level of at least 126 mg/dL. Levels of C-reactive protein were assayed by means of ultrasensitive nephelometry (Dade Behring, Milton Keynes, England). Definite and possible left ventricular hypertrophy was defined from the electrocardiogram in accordance with Minnesota coding criteria (Minnesota codes 3.1 and 3.3).29 Estimated glomerular filtration rate (eGFR), estimated from the serum creatinine level using the Modification of Diet in Renal Disease equation developed by Levey et al,3032 was used as a measure of renal function.

ADIPONECTIN CONCENTRATIONS

Plasma adiponectin concentrations were determined using an enzyme-linked immunosorbent assay (R&D Systems Europe Ltd, Abingdon, England). The intra-assay and the interassay coefficients of variability were each 7.5%. We have previously shown this method to correlate well with a radioimmunoassay method for adiponectin measurement.11 Adiponectin concentrations were not available in 206 men. There is no evidence that the adipokine levels measured in the present study were influenced by prolonged storage or repeated free-thawing of samples.

RECALL OF PHYSICIAN DIAGNOSIS OF CVD AT REEXAMINATION

The men were asked whether a physician had ever told them that they had angina or myocardial infarction (MI) (ie, heart attack or coronary thrombosis), heart failure, stroke, diabetes mellitus, or any of a number of other CVD conditions. Patient recall of a physician diagnosis of CVD has been shown to be a valid measure of recording diseases in this study population.33,34 The κ statistics comparing the medical record review with the patient's recall of coronary heart disease was 0.82.33 The men were also asked about regular treatment.

FOLLOW-UP

All men have been followed up from the initial 1978-1980 examination for cardiovascular morbidity, and follow-up has been achieved for 99% of the cohort.35 In the present analyses, all-cause mortality is based on follow-up from the 1998-2000 rescreening (when patients were aged 60 to 79 years) to December 31, 2005, a mean follow-up of 6 years (range, 5-7 years). Information on death was collected through the established tagging procedures provided by the National Health Service registers. A nonfatal MI was diagnosed according to World Health Organization criteria.36 Cardiovascular deaths include all those with International Classification of Diseases, Ninth Revision, codes 401 to 459. Evidence regarding nonfatal MI and heart failure was obtained by ongoing reports from general practitioners, by biennial reviews of the patients' medical records (including hospital and clinic correspondence) through the end of the study period, and from repeated personal questionnaires completed by surviving subjects after the initial examination.

The results relating adiponectin to coronary heart disease events recently published by our group11 concerned samples taken at the initial 1978-1980 screening, and therefore the analyses in the present article do not overlap with those of the previous study.

MEN WITH PHYSICIAN-DIAGNOSED CVD AND HEART FAILURE

According to their recall of a physician diagnosis of CVD (MI, angina, or stroke) or heart failure at the 1998-2000 examination and regular surveillance of general practitioners' medical records of major nonfatal MI, stroke, or heart failure occurring before that point, the men were divided into the following 3 groups on the basis of their cardiovascular and heart failure status: (1) those with no prevalent physician-diagnosed CVD (MI, angina, or stroke) or heart failure (n = 3099); (2) those with prevalent physician-diagnosed CVD but no diagnosed heart failure (n = 830); and (3) those with prevalent physician-diagnosed heart failure (with or without CVD) (n = 117).

STATISTICAL ANALYSIS

The men were divided into 3 groups on the basis of the tertile distribution of adiponectin levels in all men. Thus, similar cutoff points were used for the adiponectin groups in men without diagnosed CVD or heart failure, in those with CVD (no heart failure), and in those with heart failure. Kaplan-Meier curves were used to construct cumulative mortality curves across the 3 adiponectin groups. We used the Cox proportional hazards model to assess the multivariate-adjusted relative risk (RR) for the adiponectin groups. In the adjustment, factors known to be associated with mortality were included. In the multivariate analysis, smoking (never, long-term ex-smokers [>15 years], recent ex-smokers [<15 years], and current smokers), social class (manual vs nonmanual work), physical activity (none/occasional, light, moderate, and moderately vigorous/vigorous),24 alcohol intake (none/occasional, light, moderate, and heavy),24 BMI (<18.5, 18.5-24.9, 25.0-30.0, and ≥30.0), eGFR (<60, 60-69, and ≥70 mL/min/1.73 m2), diabetes mellitus (yes or no), treatment of hypertension (yes or no), use of statins (yes or no), use of β-blockers (yes or no), and weight loss during the preceding 3 years (yes or no) were fitted as categorical variables. Forced expiratory volume in 1 second, homeostasis model assessment product, and levels of C-reactive protein, albumin, and high-density lipoprotein cholesterol were fitted as continuous variables. Tests for trend were performed fitting adiponectin level in its original continuous form. In Table 1 and Table 2, tests for trends were performed across the groups.

Table Graphic Jump LocationTable 1. Baseline Characteristics According to Tertiles of Adiponectin Levels in Men With and Without Diagnosed CVD, Excluding Men With Heart Failure a
Table Graphic Jump LocationTable 2. Baseline Characteristics According to Tertiles of Adiponectin Level in Men With Diagnosed Heart Failure a

During the mean follow-up period of 6 years in the 4046 men with adiponectin data, there were 734 deaths from all causes, of which 309 (42%) were due to CVD. Men with no CVD or heart failure and those with CVD only had lower adiponectin levels compared with men with heart failure (P < .001). The mean adiponectin levels in the 3 groups were 6.77 (interquartile range, 4.38-10.85), 6.63 (interquartile range, 4.10-11.38), and 9.23 (interquartile range, 6.04-15.17) μg/mL for groups 1, 2, and 3, respectively. The cumulative mortality in the 3 groups was 15.0%, 26.1%, and 44.4%, respectively.

The Figure shows the cumulative mortality according to the tertile cutoff distribution of adiponectin levels in the 3 groups. Elevated adiponectin levels were associated with the worst prognosis in men with no diagnosed CVD or heart failure and in men with heart failure (P < .001) and to a weaker extent in men with CVD without heart failure (P = .11).

Place holder to copy figure label and caption
Figure.

Kaplan-Meier curves for mortality stratified by tertiles of adiponectin levels in men with no physician-diagnosed prevalent cardiovascular disease (CVD) or heart failure (A), men with CVD but no heart failure (B), and men with physician-diagnosed heart failure (C). Tertile 1 indicates less than 5.27 μg/mL; tertile 2, 5.27 to 9.40 μg/mL; and tertile 3, 9.41 μg/mL or greater.

Graphic Jump Location
BASELINE CHARACTERISTICS

Table 1 shows the baseline characteristics by the tertiles of adiponectin level in men with and without CVD, excluding those with heart failure. In both groups, elevated adiponectin levels were associated with older age, unintentional weight loss, lower BMI, lower forced expiratory volume in 1 second, and lower albumin level, but were also associated with lower rates of diabetes mellitus, lower use of β-blockers, higher high-density lipoprotein cholesterol levels, and lower insulin resistance (homeostasis model assessment) in both groups. Elevated adiponectin levels were associated with lower C-reactive protein levels in the men with no CVD or heart failure. In the small group of men with heart failure only (Table 2), similar findings were seen.

ADIPONECTIN LEVELS AND ALL-CAUSE AND CVD MORTALITY

Table 3 shows the age-adjusted RRs and 95% confidence intervals (CIs) for all-cause mortality and CVD mortality by the tertile groups of adiponectin levels according to CVD and heart failure status. Adiponectin levels were significantly and positively associated with all-cause mortality and CVD mortality in those with no diagnosed CVD or heart failure as well as in those with heart failure. This association was strengthened after further adjustment for alcohol, smoking, BMI, social class, treated hypertension, left ventricular hypertrophy, use of β-blockers, use of statins, diabetes, lung function, levels of high-density lipoprotein cholesterol, albumin, and C-reactive protein, and homeostasis model assessment (Table 3). No significant association was seen between adiponectin levels and total or CVD mortality in those with CVD without heart failure.

Table Graphic Jump LocationTable 3. Adiponectin and Adjusted Relative Risk of All-Cause and CVD Mortality According to Presence of CVD and Heart Failure a
WEIGHT LOSS AND RENAL FUNCTION

Further adjustment for weight loss and low eGFR made minor differences to the relationships seen (Table 3). The increased risk of mortality associated with high adiponectin levels in those with no CVD was seen even after exclusion of men with low eGFR (<60 mL/min/1.73 m2) (adjusted RR, 1.50 [95% CI, 1.13-1.99]) after adjustment for factors in model 2 (Table 3) or exclusion of leaner men (BMI, <25.0) (adjusted RR, 1.89 [95% CI, 1.36-2.63]).

SMOKING AND ILL HEALTH

The positive association between adiponectin levels and mortality in those with no CVD or heart failure was seen in those who were never smokers (n = 959) (adjusted RR, 1.90 [95% CI, 0.99-3.62]) and in men who reported good or excellent health (adjusted RR, 1.42 [95% CI, 1.03-1.96]).

NONCARDIOVASCULAR DISEASE

In men with no diagnosed CVD or heart failure, elevated adiponectin levels were also associated with increased risk of mortality from noncardiovascular causes (adjusted RR, 1.46 [95% CI, 1.05-2.04; P = .04 for trend]).

In this study of elderly men aged 60 to 79 years, mean adiponectin levels were significantly higher in the older groups and significantly raised in those with physician-diagnosed heart failure. We confirm the results of previous studies that high adiponectin levels are associated with significantly increased mortality in those with heart failure.12,13 Our findings extend the link between high adiponectin levels and mortality to the general older population of men without diagnosed CVD or heart failure. This increased mortality was seen for cardiovascular and noncardiovascular causes. In men with established CVD without heart failure, high adiponectin levels showed weak positive associations with total and CVD mortality, although the findings were not statistically significant.

The elevated mortality risk associated with high adiponectin levels has been observed in several other selected populations with coronary artery disease or renal dysfunction.1417 It has been suggested that accumulation of adiponectin in those with diseases such as heart failure or chronic kidney disease, unlike the general population, may reflect the wasting and malnutrition that characterize these disease states and is thus a marker of poor prognosis.12,16 This is consistent with the high prevalence of unintentional weight loss and low albumin levels (proxy for malnutrition or cachectic state) observed in those with high adiponectin levels in the heart failure group. In the general population, however, some studies have shown high adiponectin levels to be cardioprotective with regard to CVD events,4,5 although this has not been consistent across population studies.911 We have shown that high adiponectin levels were associated with both total and CVD mortality in older men without diagnosed CVD or heart failure, which was not explained by traditional risk factors, weight loss, or renal function in multivariate analyses. The positive association was seen in never smokers, in those who reported good or excellent health, and even after exclusion of lean men (BMI, <25.0). Thus, the increased mortality does not just reflect ill health or low BMI, which has been linked to increased mortality in elderly individuals.37 These findings are in keeping with the most recent findings from the Rancho Bernardo Study, which reported high adiponectin levels to be associated with increased CVD and all-cause mortality in community-dwelling men and women.17

Adiponectin levels increase with age, and it is suggested that the decline in renal function with age may contribute to this increase.20 However, the increased risk in those with no CVD was seen even after exclusion of men with chronic kidney disease (eGFR, <60 mL/min per 1.73 m2).30

Several other possibilities could explain our findings in those with no diagnosed CVD or heart failure. Aging is associated with weight loss and loss in skeletal muscle mass and strength (sarcopenia),38,39 which are significant predictors of mortality in the elderly population.40,41 Thus, high adiponectin levels in elderly persons may be a consequence of weight loss and sarcopenia with aging. Alternatively, it may be directly responsible for increasing energy expenditure and induce weight loss through a direct effect on the brain,42 accelerating sarcopenia in elderly persons and thereby increasing mortality risk. Although the association between adiponectin and mortality remained after adjustment for weight loss, we did not have measures of skeletal muscle mass or of loss of muscle mass in general. An increased adiponectin level might be a marker for early cardiac dysfunction resulting from aging or asymptomatic CVD, increasing the risk of CVD mortality.

The strengths of this study include its representative sampling of men aged 60 to 79 years with a high follow-up rate, its good characterization of CVD status, and the availability of a wide range of risk factors and biological markers, including renal function. The eGFR estimated from serum creatinine level may not be as accurate a measure of renal function as direct measures of GFR. However, the Modification of Diet in Renal Disease Study Group equation to estimate GFR, which takes into account age, has been validated in large populations,31,32 and the eGFR significantly predicted CVD mortality in this cohort.43 The availability of data on intentional and unintentional weight loss in the 3 years prior to sampling was also a major advantage. Our study was performed in a predominantly white male population; we cannot generalize our findings to older women in whom mean adiponectin levels are about 50% higher44 or to other ethnic groups.

In conclusion, despite the favorable cardiovascular risk profile associated with high adiponectin levels, high adiponectin levels were associated with increased cardiovascular and all-cause mortality in this population of older men. The association was particularly strong in those with heart failure but, critically, was present also in those with no diagnosed heart failure or CVD. These data further stress the need to reevaluate the direction of the relationship between adiponectin concentrations and vascular morbidity and mortality in older men and suggest the need for further studies to disentangle relationships, which may help better determine any clinical role for adiponectin.

Correspondence: S. Goya Wannamethee, PhD, Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, England (goya@pcps.ucl.ac.uk).

Accepted for Publication: March 20, 2007.

Author Contributions: Dr Wannamethee had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Wannamethee and Sattar. Acquisition of data: Whincup, Lennon, and Sattar. Analysis and interpretation of data: Wannamethee. Drafting of the manuscript: Wannamethee and Lennon. Critical revision of the manuscript for important intellectual content: Whincup and Sattar. Statistical analysis: Wannamethee. Obtained funding: Wannamethee, Whincup, and Sattar. Administrative, technical, and material support: Lennon.

Financial Disclosure: None reported.

Funding/Support: This study was supported by the Department of Health (England) (British Regional Heart Study, a British Heart Foundation Research Group) and a British Heart Foundation Project grant for the adiponectin measurements and laboratory analyses reported herein (Drs Wannamethee, Whincup, and Sattar).

Disclaimer: The views expressed in this article are those of the authors and not necessarily those of the Department of Health of England.

Scherer  PEWilliams  SFogliano  MBaldini  GLodish  HF A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995;270 (45) 26746- 26749
PubMed Link to Article
Chandran  MPhillips  SACiaraldi  THenry  RR Adiponectin: more than just another fat cell hormone? Diabetes Care 2003;26 (8) 2442- 2450
PubMed Link to Article
Ouchi  NKihara  SArita  Y  et al.  Adiponectin, an adipocyte derived plasma protein, inhibits endothelial NF-κB signalling through a cAMP-dependent pathway. Circulation 2000;102 (11) 1296- 1301
PubMed Link to Article
Pischon  TGirman  CJHotamisligil  GSRifai  NHu  FBRimm  EB Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004;291 (14) 1730- 1737
PubMed Link to Article
Rothenbacher  DBrenner  HMarz  WKoenig  W Adiponectin, risk of coronary heart disease and correlations with cardiovascular risk markers. Eur Heart J 2005;26 (16) 1640- 1646
PubMed Link to Article
Zoccali  CMallamaci  FTripepi  G  et al.  Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 2002;13 (1) 134- 141
PubMed Link to Article
Becker  BKronenberg  FKielstein  JT  et al. MMKD Study Group, Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients with kidney disease: the Mild and Moderate Kidney Disease Study. J Am Soc Nephrol 2005;16 (4) 1091- 1098
PubMed Link to Article
Schulze  MBShai  IRimm  EBLi  TRifai  NHu  FB Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes 2005;54 (2) 534- 539
PubMed Link to Article
Lawlor  DADavey Smith  GEbrahim  SThompson  CSattar  N Plasma adiponectin levels are associated with insulin resistance, but do not predict future risk of coronary heart disease in women. J Clin Endocrinol Metab 2005;90 (10) 5677- 5683
PubMed Link to Article
Lindsay  RSResnick  HEZhu  J  et al.  Adiponectin and coronary heart disease: the Strong Heart Study. Arterioscler Thromb Vasc Biol 2005;25 (3) e15- e16
PubMed Link to Article
Sattar  NWannamethee  GSarwar  N  et al.  Adiponectin and coronary heart disease: a prospective study and meta-analysis. Circulation 2006;114 (7) 623- 629[published correction appears in Circulation. 2007;115 ((10)) e325
PubMed Link to Article
Kistorp  CFaber  JGalatius  S  et al.  Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation 2005;112 (12) 1756- 1762
PubMed Link to Article
George  JPatal  SWexler  D  et al.  Circulating adiponectin concentrations in patients with congestive heart failure. Heart 2006;92 (10) 1420- 1424
PubMed Link to Article
Cavusoglu  ERuwende  CChopra  V  et al.  Adiponectin is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction in patients presenting with chest pain. Eur Heart J 2006;27 (19) 2300- 2309[published online ahead of print July24 2006
PubMed Link to Article
Pilz  SMangge  HWellnitz  B  et al.  Adiponectin and mortality in patients undergoing coronary angiography. J Clin Endocrinol Metab 2006;91 (11) 4277- 4286
PubMed Link to Article
Menon  VLi  LWang  X  et al.  Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol 2006;17 (9) 2599- 2606
PubMed Link to Article
Laughlin  GABarrett-Connor  EMay  SLangenberg  C Association of adiponectin and coronary heart disease and mortality: the Rancho Bernardo Study. Am J Epidemiol 2007;165 (2) 164- 174
PubMed Link to Article
Cnop  MHavel  PJUtzschneider  KM  et al.  Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 2003;46 (4) 459- 469
PubMed
Chen  MBergman  RNPacini  GPorte  D  Jr Pathogenesis of age-related glucose intolerance in men: insulin resistance and decreased β-cell function. J Clin Endocrinol Metab 1985;60 (1) 13- 20
PubMed Link to Article
Isobe  TSaitoh  STakagi  S  et al.  Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu Study. Eur J Endocrinol 2005;153 (1) 91- 98
PubMed Link to Article
Fried  LFShlipak  MGCrump  C  et al.  Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. J Am Coll Cardiol 2003;41 (8) 1364- 1372
PubMed Link to Article
Shaper  AGPocock  SJWalker  MCohen  NMWale  CJThomson  AG British Regional Heart Study: cardiovascular risk factors in middle-aged men in 24 towns. Br Med J (Clin Res Ed) 1981;283 (6285) 179- 186
PubMed Link to Article
Wannamethee  SGShaper  AGWhincup  PH Body fat distribution, body composition, and respiratory function in elderly men. Am J Clin Nutr 2005;82 (5) 996- 1003
PubMed
Wannamethee  SGLowe  GDOWhincup  PHRumley  AWalker  MLennon  L Physical activity and hemostatic and inflammatory variables in elderly men. Circulation 2002;105 (15) 1785- 1790
PubMed Link to Article
Wannamethee  SGShaper  AGWhincup  PHWalker  M Overweight and obesity and the burden of disease and disability in elderly men. Int J Obes 2004;28 (11) 1374- 1382
Link to Article
Emberson  JRWhincup  PHWalker  MThomas  MAlberti  KG Biochemical measures in a population based study: the effect of fasting duration and time of day. Ann Clin Biochem 2002;39 (pt 5) 493- 501
PubMed Link to Article
Bruce  NGCook  DGShaper  AG Differences between observers in blood pressure measurement with an automatic oscillometric recorder. J Hypertens Suppl 1990;8 (4) S11- S13
PubMed
Matthews  DRHosker  JPRudenski  ASNaylor  BATreacher  DFTurner  RC Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28 (7) 412- 419
PubMed Link to Article
Blackburn  HKeys  ASimonson  ERautaharju  PPunsar  S The electrocardiogram in population studies: a classification system. Circulation 1960;211160- 1175
PubMed Link to Article
Levey  ASCoresh  JBalk  E  et al. National Kidney Foundation, National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification and stratification. Ann Intern Med 2003;139 (2) 137- 147
PubMed Link to Article
Levey  ASBosch  JPLewis  JBGreene  TRogers  NRoth  DModification of Diet in Renal Disease Study Group, A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999;130 (6) 461- 470
PubMed Link to Article
Manjunath  GSarnak  MJLevey  AS Prediction equations to estimate glomerular filtration rate: an update. Curr Opin Nephrol Hypertens 2001;10 (6) 785- 792
PubMed Link to Article
Lampe  FCWalker  MLennon  LTWhincup  PHEbrahim  S Validity of a self reported history of doctor-diagnosed angina. J Clin Epidemiol 1999;52 (1) 73- 81
PubMed Link to Article
Walker  MKWhincup  PHShaper  AGLennon  LTThomson  AG Validation of patient recall of doctor-diagnosed heart attack and stroke: a postal questionnaire and record review comparison. Am J Epidemiol 1998;148 (4) 355- 361
PubMed Link to Article
Walker  MShaper  AGLennon  LWhincup  PH Twenty year follow-up of a cohort study based in general practices in 24 British towns. J Public Health Med 2000;22 (4) 479- 485
PubMed Link to Article
Rose  GBlackburn  HGillum  RFPrineas  RJ Cardiovascular Survey Methods. 2nd ed. Geneva, Switzerland World Health Organization1982;
Zamboni  MMazzali  GZoico  E  et al.  Health consequences of obesity in the elderly: a review of four unresolved questions. Int J Obes (Lond) 2005;29 (9) 1011- 1029
PubMed Link to Article
Castillo  EMGoodman-Gruen  DKritz-Silverstein  DMorton  DJWingard  DLBarrett-Connor  E Sarcopenia in elderly men and women: the Rancho Bernardo Study. Am J Prev Med 2003;25 (3) 226- 231
PubMed Link to Article
Roubenoff  R Sarcopenia: effects on body compostion and function. J Gerontol A Biol Sci Med Sci 2003;58 (11) 1012- 1017
PubMed Link to Article
Wedick  NMBarrett-Connor  EKnoke  JDWingard  DL The relationship between weight loss and all-cause mortality in older men and women with and without diabetes mellitus: the Rancho Bernardo study. J Am Geriatr Soc 2002;50 (11) 1810- 1815
PubMed Link to Article
Roubenoff  RParise  HPayette  HA  et al.  Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med 2003;115 (6) 429- 435
PubMed Link to Article
Yang  WSLee  WJFunahashi  T  et al.  Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 2001;86 (8) 3815- 3819[published correction appears in J Clin Endocrinol Metab. 2002;87 ((4)) 1626
PubMed Link to Article
Wannamethee  SGShaper  AGLowe  GDLennon  LRumley  AWhincup  PH Renal function and cardiovascular mortality in elderly men: the role of inflammatory, procoagulant, and endothelial biomarkers. Eur Heart J 2006;27 (24) 2975- 2981
PubMed Link to Article
Laughlin  GABarett-Connor  EMay  S Sex-specific determinants of serum adiponectin in older adults: the role of endogenous sex hormones. Int J Obes (Lond) 2007;31 (3) 457
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Kaplan-Meier curves for mortality stratified by tertiles of adiponectin levels in men with no physician-diagnosed prevalent cardiovascular disease (CVD) or heart failure (A), men with CVD but no heart failure (B), and men with physician-diagnosed heart failure (C). Tertile 1 indicates less than 5.27 μg/mL; tertile 2, 5.27 to 9.40 μg/mL; and tertile 3, 9.41 μg/mL or greater.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Baseline Characteristics According to Tertiles of Adiponectin Levels in Men With and Without Diagnosed CVD, Excluding Men With Heart Failure a
Table Graphic Jump LocationTable 2. Baseline Characteristics According to Tertiles of Adiponectin Level in Men With Diagnosed Heart Failure a
Table Graphic Jump LocationTable 3. Adiponectin and Adjusted Relative Risk of All-Cause and CVD Mortality According to Presence of CVD and Heart Failure a

References

Scherer  PEWilliams  SFogliano  MBaldini  GLodish  HF A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995;270 (45) 26746- 26749
PubMed Link to Article
Chandran  MPhillips  SACiaraldi  THenry  RR Adiponectin: more than just another fat cell hormone? Diabetes Care 2003;26 (8) 2442- 2450
PubMed Link to Article
Ouchi  NKihara  SArita  Y  et al.  Adiponectin, an adipocyte derived plasma protein, inhibits endothelial NF-κB signalling through a cAMP-dependent pathway. Circulation 2000;102 (11) 1296- 1301
PubMed Link to Article
Pischon  TGirman  CJHotamisligil  GSRifai  NHu  FBRimm  EB Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004;291 (14) 1730- 1737
PubMed Link to Article
Rothenbacher  DBrenner  HMarz  WKoenig  W Adiponectin, risk of coronary heart disease and correlations with cardiovascular risk markers. Eur Heart J 2005;26 (16) 1640- 1646
PubMed Link to Article
Zoccali  CMallamaci  FTripepi  G  et al.  Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 2002;13 (1) 134- 141
PubMed Link to Article
Becker  BKronenberg  FKielstein  JT  et al. MMKD Study Group, Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients with kidney disease: the Mild and Moderate Kidney Disease Study. J Am Soc Nephrol 2005;16 (4) 1091- 1098
PubMed Link to Article
Schulze  MBShai  IRimm  EBLi  TRifai  NHu  FB Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes 2005;54 (2) 534- 539
PubMed Link to Article
Lawlor  DADavey Smith  GEbrahim  SThompson  CSattar  N Plasma adiponectin levels are associated with insulin resistance, but do not predict future risk of coronary heart disease in women. J Clin Endocrinol Metab 2005;90 (10) 5677- 5683
PubMed Link to Article
Lindsay  RSResnick  HEZhu  J  et al.  Adiponectin and coronary heart disease: the Strong Heart Study. Arterioscler Thromb Vasc Biol 2005;25 (3) e15- e16
PubMed Link to Article
Sattar  NWannamethee  GSarwar  N  et al.  Adiponectin and coronary heart disease: a prospective study and meta-analysis. Circulation 2006;114 (7) 623- 629[published correction appears in Circulation. 2007;115 ((10)) e325
PubMed Link to Article
Kistorp  CFaber  JGalatius  S  et al.  Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation 2005;112 (12) 1756- 1762
PubMed Link to Article
George  JPatal  SWexler  D  et al.  Circulating adiponectin concentrations in patients with congestive heart failure. Heart 2006;92 (10) 1420- 1424
PubMed Link to Article
Cavusoglu  ERuwende  CChopra  V  et al.  Adiponectin is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction in patients presenting with chest pain. Eur Heart J 2006;27 (19) 2300- 2309[published online ahead of print July24 2006
PubMed Link to Article
Pilz  SMangge  HWellnitz  B  et al.  Adiponectin and mortality in patients undergoing coronary angiography. J Clin Endocrinol Metab 2006;91 (11) 4277- 4286
PubMed Link to Article
Menon  VLi  LWang  X  et al.  Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol 2006;17 (9) 2599- 2606
PubMed Link to Article
Laughlin  GABarrett-Connor  EMay  SLangenberg  C Association of adiponectin and coronary heart disease and mortality: the Rancho Bernardo Study. Am J Epidemiol 2007;165 (2) 164- 174
PubMed Link to Article
Cnop  MHavel  PJUtzschneider  KM  et al.  Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 2003;46 (4) 459- 469
PubMed
Chen  MBergman  RNPacini  GPorte  D  Jr Pathogenesis of age-related glucose intolerance in men: insulin resistance and decreased β-cell function. J Clin Endocrinol Metab 1985;60 (1) 13- 20
PubMed Link to Article
Isobe  TSaitoh  STakagi  S  et al.  Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu Study. Eur J Endocrinol 2005;153 (1) 91- 98
PubMed Link to Article
Fried  LFShlipak  MGCrump  C  et al.  Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. J Am Coll Cardiol 2003;41 (8) 1364- 1372
PubMed Link to Article
Shaper  AGPocock  SJWalker  MCohen  NMWale  CJThomson  AG British Regional Heart Study: cardiovascular risk factors in middle-aged men in 24 towns. Br Med J (Clin Res Ed) 1981;283 (6285) 179- 186
PubMed Link to Article
Wannamethee  SGShaper  AGWhincup  PH Body fat distribution, body composition, and respiratory function in elderly men. Am J Clin Nutr 2005;82 (5) 996- 1003
PubMed
Wannamethee  SGLowe  GDOWhincup  PHRumley  AWalker  MLennon  L Physical activity and hemostatic and inflammatory variables in elderly men. Circulation 2002;105 (15) 1785- 1790
PubMed Link to Article
Wannamethee  SGShaper  AGWhincup  PHWalker  M Overweight and obesity and the burden of disease and disability in elderly men. Int J Obes 2004;28 (11) 1374- 1382
Link to Article
Emberson  JRWhincup  PHWalker  MThomas  MAlberti  KG Biochemical measures in a population based study: the effect of fasting duration and time of day. Ann Clin Biochem 2002;39 (pt 5) 493- 501
PubMed Link to Article
Bruce  NGCook  DGShaper  AG Differences between observers in blood pressure measurement with an automatic oscillometric recorder. J Hypertens Suppl 1990;8 (4) S11- S13
PubMed
Matthews  DRHosker  JPRudenski  ASNaylor  BATreacher  DFTurner  RC Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28 (7) 412- 419
PubMed Link to Article
Blackburn  HKeys  ASimonson  ERautaharju  PPunsar  S The electrocardiogram in population studies: a classification system. Circulation 1960;211160- 1175
PubMed Link to Article
Levey  ASCoresh  JBalk  E  et al. National Kidney Foundation, National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification and stratification. Ann Intern Med 2003;139 (2) 137- 147
PubMed Link to Article
Levey  ASBosch  JPLewis  JBGreene  TRogers  NRoth  DModification of Diet in Renal Disease Study Group, A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999;130 (6) 461- 470
PubMed Link to Article
Manjunath  GSarnak  MJLevey  AS Prediction equations to estimate glomerular filtration rate: an update. Curr Opin Nephrol Hypertens 2001;10 (6) 785- 792
PubMed Link to Article
Lampe  FCWalker  MLennon  LTWhincup  PHEbrahim  S Validity of a self reported history of doctor-diagnosed angina. J Clin Epidemiol 1999;52 (1) 73- 81
PubMed Link to Article
Walker  MKWhincup  PHShaper  AGLennon  LTThomson  AG Validation of patient recall of doctor-diagnosed heart attack and stroke: a postal questionnaire and record review comparison. Am J Epidemiol 1998;148 (4) 355- 361
PubMed Link to Article
Walker  MShaper  AGLennon  LWhincup  PH Twenty year follow-up of a cohort study based in general practices in 24 British towns. J Public Health Med 2000;22 (4) 479- 485
PubMed Link to Article
Rose  GBlackburn  HGillum  RFPrineas  RJ Cardiovascular Survey Methods. 2nd ed. Geneva, Switzerland World Health Organization1982;
Zamboni  MMazzali  GZoico  E  et al.  Health consequences of obesity in the elderly: a review of four unresolved questions. Int J Obes (Lond) 2005;29 (9) 1011- 1029
PubMed Link to Article
Castillo  EMGoodman-Gruen  DKritz-Silverstein  DMorton  DJWingard  DLBarrett-Connor  E Sarcopenia in elderly men and women: the Rancho Bernardo Study. Am J Prev Med 2003;25 (3) 226- 231
PubMed Link to Article
Roubenoff  R Sarcopenia: effects on body compostion and function. J Gerontol A Biol Sci Med Sci 2003;58 (11) 1012- 1017
PubMed Link to Article
Wedick  NMBarrett-Connor  EKnoke  JDWingard  DL The relationship between weight loss and all-cause mortality in older men and women with and without diabetes mellitus: the Rancho Bernardo study. J Am Geriatr Soc 2002;50 (11) 1810- 1815
PubMed Link to Article
Roubenoff  RParise  HPayette  HA  et al.  Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med 2003;115 (6) 429- 435
PubMed Link to Article
Yang  WSLee  WJFunahashi  T  et al.  Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 2001;86 (8) 3815- 3819[published correction appears in J Clin Endocrinol Metab. 2002;87 ((4)) 1626
PubMed Link to Article
Wannamethee  SGShaper  AGLowe  GDLennon  LRumley  AWhincup  PH Renal function and cardiovascular mortality in elderly men: the role of inflammatory, procoagulant, and endothelial biomarkers. Eur Heart J 2006;27 (24) 2975- 2981
PubMed Link to Article
Laughlin  GABarett-Connor  EMay  S Sex-specific determinants of serum adiponectin in older adults: the role of endogenous sex hormones. Int J Obes (Lond) 2007;31 (3) 457
PubMed Link to Article

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