Cystatin C and Cardiovascular Disease

Background Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. Objectives The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. Methods We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. Results Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 × 10−14). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 × 10−211), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0.994), which was statistically different from the observational estimate (p = 1.6 × 10−5). A causal effect of cystatin C was not detected for any individual component of CVD. Conclusions Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD

Is Species Richness Congruent Among Taxa? Surrogacy, Complementarity, And Environmental Correlates Among Three Disparate Taxa In Geographically Isolated Wetlands

Globally, there is a growing awareness that geographically isolated wetlands contribute to important landscape functions and ecological services. One of their most important functions is providing habitat to a diverse fauna and flora adapted to variable wet and dry environments. We focus on analysis of similarities among three distinct taxa, vascular plants, aquatic beetles, and amphibians, in isolated wetlands in the southeastern coastal plain of Georgia. Although species richness for these three taxa is quite high in isolated wetlands at a regional scale, we found a low degree of congruence in species richness and species composition among taxa. This finding demonstrates that none of these groups could be used as a surrogate for the overall biodiversity of these wetlands represented by the three taxa. We identified environmental factors influencing the complex patterns of species richness and distribution for the three groups that indicate biotic and abiotic processes operate at different scales for each taxonomic group and for individual species. Our study illustrates the importance of considering structural diversity, hydrologic variation, and landscape position as key elements to understanding overall diversity represented by the three taxa in isolated wetlands and in developing assessment tools of wetland condition. © 2011 Elsevier Ltd. All rights reserved