Calcific aortic stenosis has many characteristics in common with atherosclerosis, including hypercholesterolemia. We hypothesized that intensive lipid-lowering therapy would halt the progression of ...calcific aortic stenosis or induce its regression.
In this double-blind, placebo-controlled trial, patients with calcific aortic stenosis were randomly assigned to receive either 80 mg of atorvastatin daily or a matched placebo. Aortic-valve stenosis and calcification were assessed with the use of Doppler echocardiography and helical computed tomography, respectively. The primary end points were change in aortic-jet velocity and aortic-valve calcium score.
Seventy-seven patients were assigned to atorvastatin and 78 to placebo, with a median follow-up of 25 months (range, 7 to 36). Serum low-density lipoprotein cholesterol concentrations remained at 130+/-30 mg per deciliter in the placebo group and fell to 63+/-23 mg per deciliter in the atorvastatin group (P<0.001). Increases in aortic-jet velocity were 0.199+/-0.210 m per second per year in the atorvastatin group and 0.203+/-0.208 m per second per year in the placebo group (P=0.95; adjusted mean difference, 0.002; 95 percent confidence interval, -0.066 to 0.070 m per second per year). Progression in valvular calcification was 22.3+/-21.0 percent per year in the atorvastatin group, and 21.7+/-19.8 percent per year in the placebo group (P=0.93; ratio of post-treatment aortic-valve calcium score, 0.998; 95 percent confidence interval, 0.947 to 1.050).
Intensive lipid-lowering therapy does not halt the progression of calcific aortic stenosis or induce its regression. This study cannot exclude a small reduction in the rate of disease progression or a significant reduction in major clinical end points. Long-term, large-scale, randomized, controlled trials are needed to establish the role of statin therapy in patients with calcific aortic stenosis.
High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin ...release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome.
Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm(2)) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact of REgression (SALTIRE) study, had long-term follow-up for the occurrence of aortic valve replacement (AVR) and cardiovascular deaths. Over a median follow-up of 10.6 years (1178 patient-years), 24 patients died from a cardiovascular cause and 60 patients had an AVR. Plasma cTnI concentrations were associated with AVR or cardiovascular death HR 1.77 (95% CI, 1.22 to 2.55) independent of age, sex, systolic ejection fraction, and aortic stenosis severity.
In patients with aortic stenosis, plasma cTnI concentration is associated with advanced hypertrophy and replacement myocardial fibrosis as well as AVR or cardiovascular death.
In order to evaluate alternative agricultural production methods that may reduce environmental impacts, assessment tools are required that measure the consequences of changing systems. This paper ...explores the usefulness of Life Cycle Assessment (LCA) in identifying environmental improvement opportunities in horticultural systems. LCA has been applied to three commercial apple (
Malus x domestica, Borkh.) orchards and two reference orchards, representing standard practices according to expert advice, in New Zealand. Variability observed in the results suggests growers’ technique exerts considerable impact on the LCA results, introducing variances of 30–50% in energy consumption and other environmental impacts when performing the same field operation. Despite a small sample size, the origins of the environmental impacts resulting from these examples of Integrated Fruit Production (IFP) were observed to be generally similar. Human toxicity related impacts were dominated by emissions of the synthetic pesticides used in IFP, and were thoroughly modelled in the study. The production of pesticides and agricultural machinery was found to be significant in the overall energy consumption of the orchard; pesticide production represented 10–20% of energy consumption, while machinery production accounted for 7–12% of energy consumption in all study sites. The application of LCA helped to identify improvement opportunities to reduce environmental impacts within this and related production systems, and demonstrated its usefulness in setting priorities to realise these opportunities. LCA is a holistic approach that measures the different environmental impacts from agriculture and is useful for the development of certification schemes such as EUREP GAP, or the assessment of the environmental soundness of agricultural technologies.
Aphid transmission is a major factor in the formation of citrus tristeza virus (CTV) populations. Here, we examined the effect of population interaction on aphid transmissibility of different CTV ...genotypes. We found that there was no correlation between the proportion of viral genotypes in the source population and what was transmitted. We next examined the transmission of a poorly transmitted infectious cDNA clone (T36) in mixture with other CTV genotypes. T36 transmission increased from 0.5% alone, to up to 35.7%, depending on the coinfecting genotype. These results suggest that interaction between CTV genotypes affects the transmission of this virus.
ECG left ventricular hypertrophy with strain is associated with an adverse prognosis in aortic stenosis. We investigated the mechanisms and outcomes associated with ECG strain.
One hundred and two ...patients (age, 70 years range, 63-75 years; male, 66%; aortic valve area, 0.9 cm(2) range, 0.7-1.2 cm(2)) underwent ECG, echocardiography, and cardiovascular magnetic resonance. They made up the mechanism cohort. Myocardial fibrosis was determined with late gadolinium enhancement (replacement fibrosis) and T1 mapping (diffuse fibrosis). The relationship between ECG strain and cardiovascular magnetic resonance was then assessed in an external validation cohort (n=64). The outcome cohort was made up of 140 patients from the Scottish Aortic Stenosis and Lipid Lowering Trial Impact on Regression (SALTIRE) study and was followed up for 10.6 years (1254 patient-years). Compared with those without left ventricular hypertrophy (n=51) and left ventricular hypertrophy without ECG strain (n=30), patients with ECG strain (n=21) had more severe aortic stenosis, increased left ventricular mass index, more myocardial injury (high-sensitivity plasma cardiac troponin I concentration, 4.3 ng/L interquartile range, 2.5-7.3 ng/L versus 7.3 ng/L interquartile range, 3.2-20.8 ng/L versus 18.6 ng/L interquartile range, 9.0-45.2 ng/L, respectively; P<0.001) and increased diffuse fibrosis (extracellular volume fraction, 27.4±2.2% versus 27.2±2.9% versus 30.9±1.9%, respectively; P<0.001). All patients with ECG strain had midwall late gadolinium enhancement (positive and negative predictive values of 100% and 86%, respectively). Indeed, late gadolinium enhancement was independently associated with ECG strain (odds ratio, 1.73; 95% confidence interval, 1.08-2.77; P=0.02), a finding confirmed in the validation cohort. In the outcome cohort, ECG strain was an independent predictor of aortic valve replacement or cardiovascular death (hazard ratio, 2.67; 95% confidence interval, 1.35-5.27; P<0.01).
ECG strain is a specific marker of midwall myocardial fibrosis and predicts adverse clinical outcomes in aortic stenosis.
The mechanism of cross-protection, the deliberate infection of plants with a “mild” virus isolate to protect against “severe” isolates, has long been a topic of debate. In our model system, Citrus ...tristeza virus (CTV), this appears to be genotype-specific superinfection-exclusion, suggesting a simple recipe for cross-protection. However, this concept failed in field trials, which led us to examine the process of superinfection-exclusion more closely. We found that exclusion relies on the relative fitness of the primary versus the challenge isolates, and the host infected, and that significant differences in superinfection success could occur between isolates that differ by as few as 3 nucleotides. Furthermore, we found that exclusion was not uniform throughout the plant, but was tissue-specific. These data suggest that cross-protection is not a simple like-for-like process but a complex interaction between the primary and challenge isolates and the host.
•Superinfection-exclusion is not a simple genotype-specific like-for-like process.•Isolate fitness and host species determine the outcome of superinfection.•Even small changes of a few nucleotides can alter the success or failure of superinfection.
Abstract Virus tropism is a result of interactions between virus, host and vector species, and determines the fate of an infection. In this study, we examined the infection process of Citrus tristeza ...virus (CTV) in susceptible and resistant species, and found that the tropism of CTV is not simply phloem limited, but tissue specific. In resistant species, virus infection was not prevented, but mostly restricted to the roots. This phenomenon was also observed after partial replacement of genes of one CTV strain from another, despite both parental strains being capable of systemic infection. Finally, the roots remained susceptible in the absence of viral gene products needed for systemic infection of shoots. Our results suggest that all phloem cells within a plant are not equally susceptible and that changes in host or virus may produce a novel tropism: restriction by the host to a location where further virus spread is prevented.
Viruses often infect plants as a mixed population. The dynamics of viral populations dictate the success of the infection, yet there is little understanding of the factors that influence them. It is ...known that temperature can affect individual viruses; could it also affect a virus population? In order to study this, we observed citrus tristeza virus (CTV) populations in different hosts under winter and summer conditions (25 versus 36 °C). We found that only some CTV strains were affected by a higher summer temperature, which lead to a change in CTV population structure, and that this effect was host dependent.
Objectives: To evaluate the effect of intensive lipid-lowering treatment on coronary artery calcification in a substudy of a trial recruiting patients with calcific aortic stenosis. Methods: In a ...double blind randomised controlled trial, 102 patients with calcific aortic stenosis and coronary artery calcification were randomly assigned by the minimisation technique to atorvastatin 80 mg daily or matched placebo. Coronary artery calcification was assessed annually by helical computed tomography. Results: 48 patients were randomly assigned to atorvastatin and 54 to placebo with a median follow up of 24 months (interquartile range 24–30). Baseline characteristics and coronary artery calcium scores were similar in both groups. Atorvastatin reduced serum low density lipoprotein cholesterol (−53%, p < 0.001) and C reactive protein (−49%, p < 0.001) concentrations whereas there was no change with placebo (−7% and 17%, p > 0.95 for both). The rate of change in coronary artery calcification was 26%/year (0.234 (SE 0.037) log arbitrary units (AU)/year; n = 39) in the atorvastatin group and 18%/year (0.167 (SE 0.034) log AU/year; n = 49) in the placebo group, with a geometric mean difference of 7%/year (95% confidence interval −3% to 18%, p = 0.18). Serum low density lipoprotein concentrations were not correlated with the rate of progression of coronary calcification (r = 0.05, p = 0.62). Conclusion: In contrast to previous observational studies, this randomised controlled trial has shown that, despite reducing systemic inflammation and halving serum low density lipoprotein cholesterol concentrations, statin treatment does not have a major effect on the rate of progression of coronary artery calcification.
Citrus tatter leaf virus (CLTV) is globally distributed wherever citrus is grown, and, given the extensive use of CTLV sensitive rootstock, has the potential to be a significant threat to the citrus ...industry. In order to facilitate fast and reliable detection of this virus, we have developed a CTLV-specific real-time RT-qPCR assay. The optimized assay was found to be more reliable and sensitive compared to ELISA and end-point RT-PCR, detecting CTLV in up to 70% more plants. The real-time RT-qPCR is also specific, as it did not cross-react with the closely related Apple stem grooving virus or with the host itself; robust, being able to detect CTLV in young and mature host tissue types; and rapid.
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