Reconstructing Late Quaternary precipitation and its source on the southern Cape coast of South Africa: A multi-proxy paleoenvironmental record from Vankervelsvlei

The Late Quaternary climate history of South Africa and, in particular, potential changes in atmospheric circulation have been subject to considerable debate. To some extent, this is due to a scarcity of natural archives, and on the other hand the available indirect hydrological proxies are not suited to distinguishing between precipitation originating from temperate Westerlies and tropical Easterlies. This study presents a paleoenvironmental record from Vankervelsvlei, a wetland located on the southern Cape coast in the year-round rainfall zone of South Africa. A 15 m long sediment record was retrieved from this site and analysed using a multi-proxy approach. This includes, for the first time in this region, analysis of both compound-specific δ2H and δ18O from leaf wax-derived n-alkanes and hemicellulose-derived sugars, respectively, to investigate hydrological changes during the Late Quaternary. Our data suggest the driest conditions of the past ∼250 ka likely occurred from MIS 6 to MIS 5e, which still caused sediment deposition at Vankervelsvlei, and MIS 2, during which time there was an absence of sedimentation. Moist conditions occurred from MIS 5e to 5a and during parts of MIS 3, while drier conditions prevailed between MIS 5a and early MIS 3 and at the transition from MIS 3 to MIS 2. Besides changes in the amount and proportional contribution of precipitation contributions from Westerlies during glacial and Easterlies during interglacial periods, relative sea-level change affected the continentality of Vankervelsvlei, with a distinct impact on the sites hydrological balance. High-resolution analyses of the Middle- and Late-Holocene parts of the record show moist conditions and increased Easterly/locally-derived summer precipitation contributions from 7230 +160/−210 to 4890 +280/−180 cal BP and after 2840 +350/−330 cal BP. Dry conditions, accompanied by the reduction of Easterly/locally-derived summer rainfall and increased seasonality occurred from 4890 +280/−180 to 2840 +350/−330 cal BP. Our findings highlight that source and seasonality of precipitation play a major role in the hydrological balance of the southern Cape coastal region. By comparing the Vankervelsvlei record to other regional studies, we infer a coherent trend in the overall moisture evolution along South Africa's southern Cape coast during the Late Quaternary. </p

Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure.

BACKGROUND: Secretion of adrenomedullin (ADM) is stimulated by volume overload to maintain endothelial barrier function, and higher levels of biologically active (bio-) ADM in heart failure (HF) are a counteracting response to vascular leakage and tissue oedema. This study aimed to establish the value of plasma bio-ADM as a marker of congestion in patients with worsening HF. METHODS AND RESULTS: The association of plasma bio-ADM with clinical markers of congestion, as well as its prognostic value was studied in 2179 patients with new-onset or worsening HF enrolled in BIOSTAT-CHF. Data were validated in a separate cohort of 1703 patients. Patients with higher plasma bio-ADM levels were older, had more severe HF and more signs and symptoms of congestion (all P < 0.001). Amongst 20 biomarkers, bio-ADM was the strongest predictor of a clinical congestion score (r2  = 0.198). In multivariable regression analysis, higher bio-ADM was associated with higher body mass index, more oedema, and higher fibroblast growth factor 23. In hierarchical cluster analysis, bio-ADM clustered with oedema, orthopnoea, rales, hepatomegaly and jugular venous pressure. Higher bio-ADM was independently associated with impaired up-titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers after 3 months, but not of beta-blockers. Higher bio-ADM levels were independently associated with an increased risk of all-cause mortality and HF hospitalization (hazard ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.002, per log increase). Analyses in the validation cohort yielded comparable findings. CONCLUSIONS: Plasma bio-ADM in patients with new-onset and worsening HF is associated with more severe HF and more oedema, orthopnoea, hepatomegaly and jugular venous pressure. We therefore postulate bio-ADM as a congestion marker, which might become useful to guide decongestive therapy

Proenkephalin and prognosis in heart failure with preserved ejection fraction: a GREAT network study.

BACKGROUND: Proenkephalin (PENK), a stable endogenous opioid biomarker related to renal function, has prognostic utility in acute and chronic heart failure. We investigated the prognostic utility of PENK in heart failure with preserved ejection fraction (HFpEF), and its relationship to renal function, Body Mass Index (BMI), and imaging measures of diastolic dysfunction. METHODS: In this multicentre study, PENK was measured in 522 HFpEF patients (ejection fraction > 50%, 253 male, mean age 76.13 ± 10.73 years) and compared to 47 age and sex-matched controls. The primary endpoint was 2-years composite of all-cause mortality and/or heart failure rehospitalisation (HF). A subset (n = 163) received detailed imaging studies. RESULTS: PENK levels were raised in HFpEF (median [interquartile range] 88.9 [62.1-132.0]) compared to normal controls (56.3 [47.9-70.5]). PENK was correlated to urea, eGFR, Body Mass Index and E/e' (rs 0.635, - 0.741, - 0.275, 0.476, respectively, p < 0.0005). During 2 years follow-up 144 patients died and 220 had death/HF endpoints. Multivariable Cox regression models showed PENK independently predicted 2 year death/HF [hazard ratio (for 1 SD increment of log-transformed biomarker) HR 1.45 [95% CI 1.12-1.88, p = 0.005]], even after adjustment for troponin (HR 1.59 [1.14-2.20, p = 0.006]), and Body Mass Index (HR 1.63 [1.13-2.33, p = 0.009]). PENK showed no interaction with ejection fraction status for prediction of poor outcomes. Net reclassification analyses showed PENK significantly improved classification of death/HF outcomes for multivariable models containing natriuretic peptide, troponin and Body Mass Index (p < 0.05 for all). CONCLUSIONS: In HFpEF, PENK levels are related to BMI, and measures of diastolic dysfunction and are prognostic for all-cause mortality and heart failure rehospitalisation