Cystatin C Is Not Causally Related to Coronary Artery Disease

Background

Strong and independent associations between plasma concentration of cystatin C and risk of cardiovascular disease (CVD) suggests causal involvement of cystatin C.

Aim

The aim of our study was to assess whether there is a causal relationship between plasma concentration of cystatin C and risk of coronary artery disease (CAD) using a Mendelian Randomization approach.

Methods

We estimated the strength of association of plasma cystatin C on CAD risk and the strength of association of the strongest GWAS derived cystatin C SNP (rs13038305) on plasma cystatin C in the population-based Malmö Diet and Cancer Study (MDC) and thereafter the association between rs13038305 and CAD in the MDC (3200 cases of CAD and 24418 controls) and CARDIOGRAM (22233 cases of CAD and 64762 controls).

Results

Each standard deviation (SD) increment of plasma cystatin C was associated with increased risk of CAD (OR = 1.20, 95% CI 1.07–1.34) after full adjustment. Each copy of the major allele of rs13038305 was associated with 0.34 SD higher plasma concentration of cystatin C (P<1 x 10^-35), resulting in a power of >98% to detect a significant relationship between rs13038305 and CAD in MDC and CARDIOGRAM pooled. The odds ratio for CAD (per copy of the major rs13038305 allele) was 1.00 (0.94–1.07); P = 0.92 in MDC, 0.99 (0.96–1.03); P = 0.84 in CARDIOGRAM and 1.00 (0.97–1.03); P = 0.83 in MDC and CARDIOGRAM pooled.

Conclusion

Genetic elevation of plasma cystatin C is not related to altered risk of CAD, suggesting that there is no causal relationship between plasma cystatin C and CAD. Rather, the association between cystatin C and CAD appears to be due to the association of eGFR and CAD.     

Disability Pension at the Time of Coronary Revascularisation Is Associated with Higher Five-Year Mortality; A Swedish Nationwide,Register-Based Prospective Cohort Study

Background

Although coronary revascularisation by coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are common procedures, little is known regarding disability pension (DP) at the time of coronary revascularisation and its association with mortality. The aim was to investigate the five-year mortality following a first coronary revascularisation among women and men on DP, compared with those not on DP at the time of intervention, accounting for socio-demographic and medical factors.

Material and Methods

A nationwide prospective population-based cohort study was conducted, using national registers including 70,040 patients (80% men), aged 30–64 years, with a first CABG (n = 24,987; 36%) or PCI (n = 45,053; 64%) during 1994–2006 in Sweden, who were alive 30 days after the intervention. The main outcome was all-cause and cause-specific mortality within five years or through 31 December 2006, following CABG and PCI, and the exposure was DP at the time of a first coronary revascularisation. Information on DP, patient characteristics, date and cause of death was obtained from nationwide registers. Hazard ratios (HR) with 95% confidence intervals (CI) for the outcome were estimated, using Cox proportional hazard regression analyses. All analyses were stratified by type of intervention and gender.

Findings

Four percent died following coronary revascularisation. Cardiovascular disease was the most common cause of death (54%), followed by neoplasms (25%). Regardless of type of intervention, gender and after multivariable adjustments, patients on DP had a higher HR for five-year mortality compared with those not on DP at time of revascularisation (CABG: women HR 2.14; 95% CI 1.59–2.89, men HR 2.09; 1.84–2.38, PCI: women HR 2.25; 1.78–2.83, men HR 1.95; 1.72–2.21). Young women on DP at the time of PCI had a substantially higher HR (HR 4.10; 95% CI: 2.25–7.48).

Conclusion

Patients on DP at the time of first coronary revascularisation had a higher five-year risk of mortality compared with those not on DP.     

Biodegradable polymers from renewable sources: rheological characterization of hemicellulose-based hydrogels

Hemicellulose-based hydrogels were prepared by radical polymerization of 2-hydroxyethyl methacrylate or poly(ethylene glycol) dimethacrylate with oligomeric hydrosoluble hemicellulose modified with well-defined amounts of methacrylic functions. The polymerization reaction was carried out in water at 40 degrees C using a redox initiator system. The hydrogels were in general elastic, soft, and easily swellable in water. Their viscoelastic properties were determined by oscillatory shear measurements on 2 mm thick hydrogels under a slight compression to avoid slip, over the frequency range 10(-1) to 10(2). The rheological characterization indicated that the elastic response of the hydrogels was stronger than the viscous response, leading to the conclusion that the hydrogel systems displayed a predominantly solid-like behavior. The curves showed an increase in shear storage modulus with increasing cross-linking density. The nature of the synthetic comonomer in the hemicellulose-based hydrogels also influenced the shear storage modulus. Comparison of hemicellulose-based hydrogels with pure poly(2-hydroxyethyl methacrylate) hydrogels showed that their behaviors were rather similar, demonstrating that the synthetic procedure made it possible to prepare hemicellulose-based hydrogels with properties similar to those of pure poly(2-hydroxyethyl methacrylate) hydrogels.     

Limited proteolysis and biophysical characterization of the lipovitellin homology region in apolipoprotein B

Apolipoprotein B (apoB) is the essential nonexchangeable protein in chylomicrons and very low-density lipoprotein-derived lipoprotein particles, including low-density lipoprotein (LDL). ApoB has been a key target for cardiovascular research because of its essential role in the assembly, secretion, delivery, and receptor binding of LDL. The three-dimensional structure of apoB has not been determined. However, the N-terminal region of apoB is homologous to the lipid storage protein lipovitellin, which allows the modeling of this region based on the X-ray structure of lipovitellin. The model of the N-terminal 17% of apoB (B17) suggests that, like lipovitellin, B17 consists of an N-terminal beta-barrel domain, a helical domain, and a beta-sheet domain (C-sheet). Here we test the validity of this model by limited proteolysis of B17 and the characterization of individual domains expressed in Escherichia coli and insect cell systems that are consistent with the model and proteolysis data. Circular dichroism studies of the individual domains indicate that they are folded and their secondary structures are in agreement with the model. We find that the helical domain and C-sheet of apoB interact with each other in vitro, suggesting a strong interaction between these two domains, even without a covalent peptide bond linkage. Our data suggest that the three lipovitellin-like domains exist in B17. Furthermore, the domains fold independently with secondary structures and stabilities like those of intact B17.     

The systematic value of flower structure in Crotalaria and related genera of the tribe Crotalarieae (Fabaceae)

Flowers in the tribe Crotalarieae of the family Fabaceae are generally adapted to bee pollination mechanisms. Molecular systematics have recently provided a major step towards a profound insight into generic relationships, thereby creating the opportunity to re-evaluate the taxonomic and functional significance of flower structure in the tribe, with emphasis on the large genus Crotalaria. A representative sample of flowers from 211 species was dissected to record morphological character states. These data were supplemented from the literature to allow for generalizations for the tribe as a whole. Six structural–functional flower types were identified: (1) pump; (2) gullet; (3) hugging; (4) saddle; (5) tunnel and (6) brush (saddle and tunnel types described here for the first time). Crotalaria uniquely has the brush type, characterized by a rostrate keel, highly dimorphic anthers, stylar trichomes and elaborate callosities on the standard petal. Remarkably, Crotalaria and Bolusia are the only genera of the tribe Crotalarieae with callosities present in all of the species. In other genera, callosities are generally absent or infrequent. Trends towards specialization of pollination syndromes are apparent as assemblages of apomorphic states that co-occur in what we refer to here as “specialized flowers”; individual characters are labile or non-homologous (e.g. callosities) and diagnostically less valuable. Unique combinations of flower characters are often useful to support current generic concepts in Crotalarieae.     

Sickness Absence following Coronary Revascularisation. A National Study of Women and Men of Working Age in Sweden 1994-2006

Background

Evidence based and gender specific knowledge about sickness absence following coronary revascularisation is lacking. The objective was to investigate sickness absence after a first coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) among women and men in a national Swedish study.

Materials and Methods

All patients 30–63 years of age, who underwent a first CABG (n = 22,985, 16% women) or PCI (40,891, 22% women) in Sweden between 1994 and 2006 were included. Information on sickness absence, co-morbidity, and other patient characteristics was obtained from national registers. Long-term sickness absence (LTSA) was defined as >180 and >90 sick-leave days in the first sick-leave spell following CABG and PCI, respectively. Prevalence ratio (PR) and 95% confidence interval (CI) of LTSA were calculated.

Findings

LTSA followed the interventions in 41% and 36% for CABG and PCI patients, respectively. Women had more often LTSA compared with men, (CABG PR = 1.23: 95% CI 1.19–1.28 and PCI PR = 1.19; 95% CI 1.16–1.23). A history of sickness absence the year before the intervention increased the risk for LTSA after the intervention in both genders. Among women, older age, or being self employed or unemployed was associated with a lower risk for LTSA. Among men previous cardiovascular disease, diabetes and low socio-economic position increased the risk. During the observation period, there was no change in sickness absence rates among PCI patients but an increase among CABG patients adjusting for patient characteristics.

Conclusion

This national study covering a 13-year period shows that long-term sickness absence following coronary revascularisation is common in Sweden, especially among women, and is associated with socio-economic position, co-morbidity, and sickness absence during the year before the intervention. Gender specific scientific knowledge about use and effects of sickness absence following coronary revascularisation is warranted for the patients, the treating physicians, the healthcare sector, and the society.     

Effects of neuropeptide F on regeneration in <Emphasis Type="Italic">Girardia tigrina</Emphasis> (Platyhelminthes)

The effects of neuropeptide F (NPF; from Moniezia expansa) on the regeneration of Girardia tigrina were studied. The animals were decapitated and incubated in water (control) or NPF. The dynamics of the proliferation of the neoblasts in the developing tissue were studied during the course of regeneration by monitoring the mitotic index (MI). The effects of incubation in FMRFamide and GYIRFamide on the MI were also tested. The course of cephalic regeneration was followed with in vivo computer-assisted morphometry for up to 7 days. The development of the regenerating nervous system and the musculature was visualised by immunostaining with a primary antiserum to the C-terminal decapeptide of NPF (YFAIIGRPRFa) and tetramethylrhodamine-isothiocyanate-conjugated phalloidin, which stains F-actin in muscle filaments. The study showed that NPF had a stimulatory effect on the mitotic activity of the neoblasts. FMRFamide and GYIRFamide did not have this effect. NPF also stimulated the growth of the regenerating head and the growing nervous system and musculature. NPF is postulated to have a morphogenetic action in the regenerating animals. This work was supported by two grants from the Finnish Academy of Science (nos. 202685, 2004) and (no. 112090, 2006) to M.G., an RFBR grant (07-04-00452a) to N.K. and a Wellcome Trust grant (069411) to A.G.M. for which we express our gratitude.