Mellor, Adrian, Christopher Boos, David Holdsworth, Joe Begley, David Hall, Andrew Lumley, Anne Burnett, Amanda Hawkins, John O'Hara, Stephen Ball, and David Woods. Cardiac biomarkers at high altitude. High Alt Med Biol 15:452–458, 2014.—Background: Classically, biomarkers such as the natriuretic peptides (NPs) BNP/NT-proBNP are associated with the diagnosis of heart failure and hs-cTnT with acute coronary syndromes. NPs are also elevated in pulmonary hypertension. High pulmonary artery systolic pressure (PASP) is a key feature of high altitude pulmonary edema (HAPE), which may be difficult to diagnose in the field. We have previously demonstrated that NPs are associated with high PASP and the presence of acute mountain sickness (AMS) in a small cohort at HA. We aimed to investigate the utility of several common cardiac biomarkers in diagnosing high PASP and AMS.
Methods:
48 participants were assessed post-trekking and at rest at three altitudes: 3833 m, 4450 m, and 5129 m. NPs, hs-cTnT and hsCRP, were quantified using immunoassays, PASP was measured by echocardiography, and AMS scores were recorded.
Results:
Significant changes occurred with ascent in NPs, hs-cTnT, hsCRP (all p<0.001) and PASP (p=0.006). A high PASP (≥40 mm Hg) was associated with higher NPs, NT-proBNP: 137±195 vs. 71.8±68 (p=0.001); BNP 15.3±18.1 vs. 8.7±6.6 (p=0.001). NPs were significantly higher in those with AMS or severe AMS vs. those without (severe AMS: NT-proBNP: 161.2±264 vs. 76.4±82.5 (p=0.008)). The NPs correlated with hsCRP. cTnT increased with exercise at HA and was also higher in those with a high PASP (13.8±21 vs. 7.8±6.5, p=0.018).
Conclusion:
The NPs and hs-cTnT are associated with high PASP at HA and the NPs with AMS.
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References
1.
BaileyDM, KlegerGR, HolzgraefeM, BallmerPE, and BartschP. (2004). Pathophysiological significance of peroxidative stress, neuronal damage, and membrane permeability in acute mountain sickness. J Appl Physiol, 96:1459–1463.
2.
BartschP, MairbaurlH, MaggioriniM, and SwensonER. (2005). Physiological aspects of high-altitude pulmonary edema. J Appl Physiol (1985), 98:1101–1110.
3.
BlythKG, GroenningBA, MarkPB, MartinTN, FosterJE, SteedmanT, MortonJJ, DargieHJ, and PeacockAJ. (2007). NT-proBNP can be used to detect right ventricular systolic dysfunction in pulmonary hypertension. Eur Respir J, 29:737–744.
4.
BoldanovaT, NoveanuM, BreidhardtT, PotockiM, ReichlinT, TaegtmeyerA, ChristM, LauleK, StelzigC, and MuellerC. (2010). Impact of history of heart failure on diagnostic and prognostic value of BNP: Results from the B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) study. Int J Cardiol, 142:265–272.
5.
BoosCJ, HoldsworthDA, WoodsDR, GreenK, NaylorJ, and MellorA. (2013). Cardiac biomarkers and high altitude pulmonary edema. Int J Cardiol, 167:e65–66.
6.
BoosCJ, MellorA, BegleyJ, StaceyM, SmithC, HawkinsA, and WoodsDR. (2014). The effects of exercise at high altitude on high-sensitivity cardiac troponin release and associated biventricular cardiac function. Clin Res Cardiol, 103:291–299.
7.
CasalsG, RosJ, SionisA, DavidsonMM, Morales-RuizM, and JimenezW. (2009). Hypoxia induces B-type natriuretic peptide release in cell lines derived from human cardiomyocytes. Am J Physiol Heart Circ Physiol, 297:H550–555.
8.
ClericoA, Del RyS, MaffeiS, PronteraC, EmdinM, and GiannessiD. (2002). The circulating levels of cardiac natriuretic hormones in healthy adults: Effects of age and sex. Clin Chem Lab Med, 40:371–377.
9.
Due-AndersenR, Pedersen-BjergaardU, Hoi-HansenT, OlsenNV, KistorpC, FaberJ, BoomsmaF, and ThorsteinssonB. (2008). NT-pro-BNP during hypoglycemia and hypoxemia in normal subjects: Impact of renin-angiotensin system activity. J Appl Physiol (1985), 104:1080–1085.
10.
DuttaroyS, ThorellD, KarlssonL, and BorjessonM. (2012). A single-bout of one-hour spinning exercise increases troponin T in healthy subjects. Scand Cardiovasc J, 46:2–6.
11.
EijsvogelsTM, VeltmeijerMT, GeorgeK, HopmanMT, and ThijssenDH. (2012). The impact of obesity on cardiac troponin levels after prolonged exercise in humans. Eur J Appl Physiol, 112:1725–1732.
12.
GaoM, WangR, JiayongZ, LiuY, and SunG. (2013). NT-ProBNP levels are moderately increased in acute high-altitude pulmonary edema. Exp Therap Med, 5:1434–1438.
13.
GoetzeJP, MogelvangR, MaageL, ScharlingH, SchnohrP, SogaardP, RehfeldJF, and JensenJS. (2006) Plasma pro-B-type natriuretic peptide in the general population: Screening for left ventricular hypertrophy and systolic dysfunction. Eur Heart J, 27:3004–3010.
14.
GrunigE, MerelesD, HildebrandtW, SwensonER, KublerW, KuechererH, and BartschP. (2000). Stress Doppler echocardiography for identification of susceptibility to high altitude pulmonary edema. J Am Coll Cardiol, 35:980–987.
15.
HackettPH, and OelzO. (1992). The Lake Louise consensus on the quantification of altitude illness. In: SuttonJR, HoustonCS, G C (eds), Hypoxia and Mountain Medicine. Queen City Printers, Burlington, VT, pp 327–330.
16.
HallC. (2005). NT-ProBNP: The mechanism behind the marker. J Card Fail, 11:S81–83.
17.
HartmannG, TschopM, FischerR, BidlingmaierC, RiepiR, TschopK, HautmannH, EndresS, and ToepferM. (2000). High altitude increases circulating interleukin-6, interleukin-1 receptor antagonist and C-reactive protein. Cytokine, 12:246–252.
18.
Hew-ButlerT, NoakesTD, SoldinSJ, and VerbalisJG. (2008). Acute changes in endocrine and fluid balance markers during high-intensity, steady-state, and prolonged endurance running: Unexpected increases in oxytocin and brain natriuretic peptide during exercise. Eur J Endocrinol, 159:729–737.
19.
Legaz-ArreseA, GeorgeK, Carranza-GarciaLE, Munguia-IzquierdoD, Moros-GarciaT, and Serrano-OstarizE. (2011). The impact of exercise intensity on the release of cardiac biomarkers in marathon runners. Eur J Appl Physiol, 111:2961–2967.
20.
MaggioriniM, BuhlerB, WalterM, and OelzO. (1990). Prevalence of acute mountain sickness in the Swiss Alps. BMJ, 301:853–855.
21.
MaggioriniM, MelotC, PierreS, PfeifferF, GreveI, SartoriC, LeporiM, HauserM, ScherrerU, and NaeijeR. (2001). High-altitude pulmonary edema is initially caused by an increase in capillary pressure. Circulation, 103:2078–2083.
22.
McCulloughPA, and SandbergKR. (2003). B-type natriuretic peptide and renal disease. Heart Fail Rev, 8:355–358.
23.
NagayaN, NishikimiT, UematsuM, SatohT, KyotaniS, SakamakiF, KakishitaM, FukushimaK, OkanoY, NakanishiN, MiyatakeHK, and KangawaK. (2000). Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation, 102:865–870.
24.
PiechotaM, BanachM, IrzmanskiR, MisztalM, RyszJ, BarylskiM, Piechota-UrbanskaM, KowalskiJ, and PawlickiL. (2007). N-terminal brain natriuretic propeptide levels correlate with procalcitonin and C-reactive protein levels in septic patients. Cell Mol Biol Lett, 12:162–175.
25.
ScharhagJ, HerrmannM, UrhausenA, HaschkeM, HerrmannW, and KindermannW. (2005). Independent elevations of N-terminal pro-brain natriuretic peptide and cardiac troponins in endurance athletes after prolonged strenuous exercise. Am Heart J, 150:1128–1134.
26.
ScharhagJ, MeyerT, AuracherM, MullerM, HerrmannM, GabrielT, HerrmannW, and KindermannW. (2008) Exercise-induced increases in NT-proBNP are not related to the exercise-induced immune response. Br J Sports Med, 42:383–385.
27.
ShaveR, RossP, LowD, GeorgeK, and GazeD. (2010). Cardiac troponin I is released following high-intensity short-duration exercise in healthy humans. Int J Cardiol, 145:337–339.
28.
ShiinaY, FunabashiN, LeeK, DaimonM, SekineT, KawakuboM, TakahashiM, YajimaR, TanabeN, KuriyamaT, and KomuroI. (2009). Right atrium contractility and right ventricular diastolic function assessed by pulsed tissue Doppler imaging can predict brain natriuretic peptide in adults with acquired pulmonary hypertension. Int J Cardiol, 135:53–59.
29.
ShintaroS, YujiK, TetsuyaN, KentaK, and HiedekazuO. (2006). Change of plasma High Sensitive C-reactive protein in climbers. Jpn Med Assoc J, 49:358–364.
30.
SmithJD, CianfloneK, MartinJ, PoirierP, BroderickTL, and NoelM. (2011). Plasma adipokine and hormone changes in mountaineers on ascent to 5300 meters. Wilderness Environ Med, 22:107–114.
31.
ThygesenK, AlpertJS, SimoonsML, ChaitmanBR, WhiteHD, Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction. (2012). Third universal definition of myocardial infarction. Circulation, 126:2020–2035.
32.
ToshnerMR, ThompsonAA, IrvingJB, BaillieJK, MortonJJ, and PeacockAJ. (2008). NT-proBNP does not rise on acute ascent to high altitude. High Alt Med Biol, 9:307–310.
33.
VasanRS, BenjaminEJ, LarsonMG, LeipEP, WangTJ, WilsonPW, and LevyD. (2002). Plasma natriuretic peptides for community screening for left ventricular hypertrophy and systolic dysfunction: The Framingham Heart Study. JAMA, 288:1252–1259.
34.
VolkersM, RohdeD, ZelnikerT, WeissCS, GiannitsisE, KatusHA, and MeyerFJ. (2013). High-sensitive troponin T increase after exercise in patients with pulmonary arterial hypertension. BMC Pulm Med, 13:28.
35.
WilsonAM, RyanMC, and BoyleAJ. (2006). The novel role of C-reactive protein in cardiovascular disease: Risk marker or pathogen. Int J Cardiol, 106:291–297.
36.
WolffB, HaaseD, LazarusP, MachillK, GrafB, LestinHG, and WernerD. (2007). Severe septic inflammation as a strong stimulus of myocardial NT-pro brain natriuretic peptide release. Int J Cardiol, 122:131–136.
37.
WoodsD, HooperT, HodkinsonP, BallS, WakefordR, PeastonB, BairstoC, GreenN, and MellorA. (2011). Effects of altitude exposure on brain natriuretic peptide in humans. Eur J Appl Physiol, 111:2687–2693.
38.
WoodsDR, BegleyJ, StaceyM, SmithC, BoosCJ, HooperT, HawkinsA, HodkinsonP, GreenN, and MellorA. (2012). Severe acute mountain sickness, brain natriuretic peptide and NT-proBNP in humans. Acta Physiol (Oxf), 205:349–355.
39.
WoodsDR, MellorA, BegleyJ, StaceyM, O'HaraJ, KawkinsA, YarkerJ, FoxenS, SmithC, and BoosC. (2013). Brain natriuretic peptide and NT-proBNP levels reflect pulmonary artery systolic pressure in trekkers at high altitude. Physioll Res/Acad Sci Bohemoslovaca, 62:597–603.
40.
YockPG, and PoppRL. (1984). Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation, 70:657–662.
