Copeptin predicts coronary artery disease cardiovascular and total mortality

Tasevska, Irina; Enhörning, Sofia; Persson, Margaretha; Nilsson, Peter M.; Melander, Olle

doi:10.1136/heartjnl-2015-308183

Cited by 73 publications

(70 citation statements)

References 29 publications

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“…In line with these findings, it was found that elevated levels of copeptin at baseline were associated with greater decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes during long-term follow-up [8] as well as with the renal end point of doubling of plasma creatinine in patients with both type 2 diabetes and albuminuria [9]. In addition, in type 2 diabetes patients treated in primary healthcare, increased levels of copeptin were associated with elevated risk of cardiovascular and all-cause mortality [10], findings in line with 2 of our own previous studies showing strong independent association between copeptin and cardiovascular morbidity and mortality, especially in patients with diabetes [11,12]. In healthy kidney donors, eGFR decreased significantly following donation but copeptin remained unchanged, suggesting that AVP, as measured by copeptin, may in fact be causally related to the decline of eGFR rather than just being a small molecule marker of eGFR [13].…”

Section: Introductionsupporting

confidence: 78%

Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population

Tasevska¹,

Enhörning²,

Christensson³

et al. 2016

Am J Nephrol

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Background: Our aim was to test if plasma copeptin, a stable surrogate marker of arginine vasopressin, predicts decline of glomerular filtration rate (GFR) and risk of chronic kidney disease (CKD). Methods: We measured copeptin and renal function at the Malmö Diet and Cancer Cardiovascular Cohort baseline exam and reassessed renal function after a follow-up time of 16.6 ± 1.5 years (n = 3,186). Furthermore, we defined CKD based on an estimated GFR (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) <60 (CKD_60_MDRD), <45 (CKD_45_MDRD) and <30 (CKD_30_MDRD) ml/min/1.73 m². Results: After multivariate adjustment (gender, age, baseline eGFR, smoking status, systolic blood pressure, antihypertensive treatment and follow-up time), copeptin (beta-coefficient per 1 SD increment of copeptin) was independently associated with significantly greater annual decline of eGFR (ml/min/1.73 m²) according to the MDRD formula (OR 0.057, 95% CI 0.022-0.093; p = 0.001) as well as according to the CKD Epidemiology Collaboration (CKD-EPI) formula (OR 0.050, 95% CI 0.022-0.077; p < 0.001). Each SD increment of copeptin independently predicted incident CKD_60_MDRD (OR 1.19, 95% CI 1.04-1.36; p = 0.010), CKD_45_MDRD (OR 1.33, 95% CI 1.04-1.71; p = 0.026) and CKD_30_MDRD (OR 3.69, 95% CI 1.41-9.66; p = 0.008). The relationship between copeptin and CKD defined by CKD-EPI gave similar results. Conclusion: Our data suggest that increased levels of copeptin independently predict decline in eGFR and greater risk of new-onset CKD.

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Section: Introductionsupporting

confidence: 78%

Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population

Tasevska¹,

Enhörning²,

Christensson³

et al. 2016

Am J Nephrol

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“…We previously showed that fasting plasma concentration of VP, measured as copeptin, strongly predicts new-onset type 2 diabetes [11], a finding later replicated in other large prospective population-based studies [12,13]. Furthermore, we showed that subjects with high copeptin concentration have an increased risk of all components of the metabolic syndrome [11,14,15] as well as cardiovascular disease and premature mortality, both in diabetics and non-diabetics [16][17][18].…”

Section: Introductionmentioning

confidence: 52%

Effects of hydration on plasma copeptin, glycemia and gluco-regulatory hormones: a water intervention in humans

et al. 2017

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Purpose High plasma copeptin, a marker of vasopressin, predicts diabetes mellitus. We tested if copeptin could be suppressed by increased water intake in healthy individuals, and if a water-induced change in copeptin was accompanied by altered concentrations of glucose, insulin or glucagon. Methods Thirty-nine healthy individuals underwent, in random order, 1 week of high water intake (3 L/day on top of habitual intake) and 1 week of normal (habitual) fluid intake (control). Fasting plasma concentrations of copeptin, glucose, insulin and glucagon were compared between the ends of both periods. Furthermore, acute copeptin kinetics were mapped for 4 h after ingestion of 1 L of water. Results After acute intake of 1 L water, copeptin was significantly reduced within 30 min, and reached maximum reduction within 90 min with on average 39% reduction (95% confidence interval (95 CI) 34-45) (p < 0.001) and remained low the entire test period (4 h). One week of increased water intake led to a 15% reduction (95 CI 5-25) (p = 0.003) of copeptin compared to control week. The greatest reduction occurred among subjects with habitually high copeptin and concentrated urine ("water-responders"). Water-responders had significant water-induced reduction of glucagon, but glucose and insulin were unaffected. Conclusions Both acute and 1 week extra water intake potently reduced copeptin concentration. In those with the greatest decline (water-responders), who are typically low drinkers with high baseline copeptin, water induced a reduction in fasting glucagon. Long-term trials assessing the effect of water on glucometabolic traits should focus on low-water drinkers with high copeptin concentration.

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“…Elevated copeptin is not only associated with increased risk of type 2 diabetes but with the entire cluster of metabolic syndrome [23, 24] especially with abdominal obesity [23, 25, 26]. Copeptin predicts not only diabetes but its main complications such as coronary artery disease and individuals with high levels of copeptin actually die earlier than people with normal values of copeptin [24, 27]. …”

Section: Association Of Vasopressin (Copeptin) Levels With Risk and Omentioning

confidence: 99%

“…Interestingly, high copeptin is also associated with a broad range of other diseases such as heart failure [28], vascular dementia [27], cognitive impairment [29], microalbuminuria [25], chronic kidney disease [17, 30], inflammatory bowel disease [31], cancer [32], and premature mortality [24]. …”

Section: Association Of Vasopressin (Copeptin) Levels With Risk and Omentioning

confidence: 99%

Two Liters a Day Keep the Doctor Away? Considerations on the Pathophysiology of Suboptimal Fluid Intake in the Common Population

Läng

Guelinckx

Lemetais

et al. 2017

Kidney Blood Press Res

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Suboptimal fluid intake may require enhanced release of antidiuretic hormone (ADH) or vasopressin for the maintenance of adequate hydration. Enhanced copeptin levels (reflecting enhanced vasopressin levels) in 25% of the common population are associated with enhanced risk of metabolic syndrome with abdominal obesity, type 2 diabetes, hypertension, coronary artery disease, heart failure, vascular dementia, cognitive impairment, microalbuminuria, chronic kidney disease, inflammatory bowel disease, cancer, and premature mortality. Vasopressin stimulates the release of glucocorticoids which in turn up-regulate the serum- and glucocorticoid-inducible kinase 1 (SGK1). Moreover, dehydration upregulates the transcription factor NFAT5, which in turn stimulates SGK1 expression. SGK1 is activated by insulin, growth factors and oxidative stress via phosphatidylinositide-3-kinase, 3-phosphoinositide-dependent kinase PDK1 and mTOR. SGK1 is a powerful stimulator of Na⁺/K⁺-ATPase, carriers (e.g. the Na⁺,K⁺,2Cl^- cotransporter NKCC, the NaCl cotransporter NCC, the Na⁺/H⁺ exchanger NHE3, and the Na⁺ coupled glucose transporter SGLT1), and ion channels (e.g. the epithelial Na⁺ channel ENaC, the Ca²⁺ release activated Ca²⁺ channel Orai1 with its stimulator STIM1, and diverse K⁺ channels). SGK1 further participates in the regulation of the transcription factors nuclear factor kappa-B NFκB, p53, cAMP responsive element binding protein (CREB), activator protein-1, and forkhead transcription factor FKHR-L1 (FOXO3a). Enhanced SGK1 activity fosters the development of hypertension, obesity, diabetes, thrombosis, stroke, inflammation including inflammatory bowel disease and autoimmune disease, cardiac fibrosis, proteinuria, renal failure as well as tumor growth. The present brief review makes the case that suboptimal fluid intake in the common population may enhance vasopressin and glucocorticoid levels thus up-regulating SGK1 expression and favouring the development of SGK1 related pathologies.

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Copeptin predicts coronary artery disease cardiovascular and total mortality

Abstract: Copeptin predicts development of CAD and cardiovascular mortality both in diabetics and non-diabetics.

Cited by 73 publications

References 29 publications

Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population

Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population

Effects of hydration on plasma copeptin, glycemia and gluco-regulatory hormones: a water intervention in humans

Two Liters a Day Keep the Doctor Away? Considerations on the Pathophysiology of Suboptimal Fluid Intake in the Common Population

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