Public health aspects of serum cholesterol

In the beginning of this century Anitschkow and De Langen started pioneering work concerning the relation between cholesterol and coronary heart disease. Both showed that there was a possible relation between cholesterol in the diet, blood cholesterol levels and atherosclerosis. It took until the second half of the twentieth century before large-scale population based studies, like the Framingham Study and the Seven Countries Study, were started to investigate the relation between serum cholesterol levels and coronary heart disease. These studies showed positive associations between serum cholesterol and incidence of and mortality from coronary heart disease in middle-aged men. Since then, other large epidemiological studies have shown that serum total cholesterol is positively associated and HDL cholesterol inversely associated with coronary heart disease mortality in middle-aged men. Quantifying the effect of cholesterol lowering interventions on for example incidence of coronary heart disease in The Netherlands is an important public health issue. Total cholesterol levels in the Dutch population are relatively high and did not substantially decrease until the beginning of the nineteen nineties. To quantify the amount of health gain that can be achieved through cholesterol lowering, additional information has to be gathered. First, recent levels of and trends in total and HDL cholesterol and prevalences of hypercholesterolemia and low HDL cholesterol levels in the Dutch population have to be described. Second, more evidence on the impact of total and HDL cholesterol on coronary heart disease in elderly men and women has to be collected. It is well known that serum total and HDL cholesterol are associated with coronary heart disease in middle-aged men and women, but it is still unclear whether this relation holds in the elderly. Third, risk functions to predict absolute risk of coronary heart disease in middle-aged men and women are well developed. However, in the elderly it is not clear whether these risk functions are a valid tool for risk prediction. This is important to know because cholesterol lowering treatment is nowadays based on the absolute level of risk, taking the total risk profile of an individual into account

Serum cholesterol is a risk factor for myocardial infarction in elderly men and women: The Rotterdam Study

Objective. To investigate the associations of serum total and HDL cholesterol with the risk of myocardial infarction in men and women of 55 years and over. Design. The Rotterdam Study is a population-based prospective cohort study. In total 2453 men and 3553 women of 55 years and older were included in this study. The mean duration of follow-up was 4 years. Main outcome measures. Relative risks were estimated with Cox's proportional- hazard analysis. Cholesterol was analysed as a continuous variable and in sex-specific quartiles. Results. In subjects aged 55 years and older the relative risk of myocardial infarction was 1.9 in men (95% confidence interval 1.1-3.3) and 3.2 in women (1.5-6.4) in the highest compared to the lowest serum total cholesterol quartile (Q4 vs. Q1). In men and women of 70 years and older, total cholesterol remained an important risk factor for myocardial infarction (Q4 vs. Q1 relative risk 3.2; 1.3-7.7 and 2.9; 1.3- 6.6, respectively). For HDL cholesterol, the relative risk in the highest compared to the lowest quartile (Q4 vs. Q1) was 0.5 in men (0.3-0.9) and 0.4 in women (0.2-0.9). HDL cholesterol was a weaker predictor in men after the age of 70 (Q4 vs. Q1 0.8; 0.3-2.1). In women of 70 years and older the relative risk was also not significant (Q4 vs. Q1 0.6; 0.3-1.3), although the trend over the quartiles was still significant. Conclusion. Serum total cholesterol remains an important risk factor for myocardial infarction in men and women aged 70 years and older, whilst HDL cholesterol at older age remains important in women only

Dynamics in cardiac surgery:trends in population characteristics and the performance of the EuroSCORE II over time

OBJECTIVESThe aim of this study was to investigate the performance of the EuroSCORE II over time and dynamics in values of predictors included in the model.METHODSA cohort study was performed using data from the Netherlands Heart Registration. All cardiothoracic surgical procedures performed between 1 January 2013 and 31 December 2019 were included for analysis. Performance of the EuroSCORE II was assessed across 3-month intervals in terms of calibration and discrimination. For subgroups of major surgical procedures, performance of the EuroSCORE II was assessed across 12-month time intervals. Changes in values of individual EuroSCORE II predictors over time were assessed graphically.RESULTSA total of 103 404 cardiothoracic surgical procedures were included. Observed mortality risk ranged between 1.9% [95% confidence interval (CI) 1.6–2.4] and 3.6% (95% CI 2.6–4.4) across 3-month intervals, while the mean predicted mortality risk ranged between 3.4% (95% CI 3.3–3.6) and 4.2% (95% CI 3.9–4.6). The corresponding observed:expected ratios ranged from 0.50 (95% CI 0.46–0.61) to 0.95 (95% CI 0.74–1.16). Discriminative performance in terms of the c-statistic ranged between 0.82 (95% CI 0.78–0.89) and 0.89 (95% CI 0.87–0.93). The EuroSCORE II consistently overestimated mortality compared to observed mortality. This finding was consistent across all major cardiothoracic surgical procedures. Distributions of values of individual predictors varied broadly across predictors over time. Most notable trends were a decrease in elective surgery from 75% to 54% and a rise in patients with no or New York Heart Association I class heart failure from 27% to 33%.CONCLUSIONSThe EuroSCORE II shows good discriminative performance, but consistently overestimates mortality risks of all types of major cardiothoracic surgical procedures in the Netherlands

Surgical repair of post-infarction ventricular free-wall rupture in the Netherlands: data from a nationwide registry

Background: Ventricular free-wall rupture (VFWR) is an infrequent but catastrophic complication of acute myocardial infarction (AMI). Most reports about outcome after surgical treatment are single-center experiences. We examined the early and mid-term outcomes after surgical repair of post-AMI VFWR using the Netherlands Heart Registration (NHR) database. Methods: We included data from NHR patients (>18 years old) who underwent surgery for post-AMI VFWR between 2014 and 2019. The primary end-point was in-hospital mortality. Secondary outcomes included postoperative complications and mid-term survival. Results: The study included 148 patients (54.7% male, mean age 66.5±11.1 years). Critical preoperative status was found in 62.6% of subjects. In-hospital mortality was 31.1% (46 of 148). Multivariable analysis identified female sex [odds ratio (OR), 5.49; 95% confidence interval (CI): 2.24–13.46] and critical preoperative status (OR, 4.06; 95% CI: 1.36–12.13) as independent predictors of in-hospital mortality. The overall median postoperative follow-up was 2.2 (interquartile range, 0.7–3.8) years. Overall survival rates at three and five years were 58.9% and 55.7%, respectively. Among hospital survivors, only 15 (14.7%) patients died during follow-up, with a five-year survival rate of 80.8%. Conclusions: In-hospital mortality after surgical repair of post-AMI VFWR is considerable. Female sex and preoperative critical status are independent predictors of early postoperative (in-hospital) death. Logistic EuroSCORE I can reliably predict in-hospital mortality (optimal cut-off >33%). Mid-term follow-up of patients surviving in-hospital course shows excellent results

The impact of surgical aortic valve replacement on quality of life-a multicenter study:a multicenter study

OBJECTIVES: To explore the effect of surgical aortic valve replacement on quality of life and the variance with age, particularly in patients at risk of deterioration. METHODS: In an observational, multicenter, cohort study of routinely collected health data, patients undergoing and electively operated between January 2011 and January 2015 with pre- and postoperative quality of life data were included. Patients were classified into 3 age groups: 5-point difference as a minimal clinically important difference. Multivariable linear regression analysis, with adjustment for confounders, was used to evaluate the association between age and quality of life. RESULTS: In 899 patients, mean physical health increased from 55 to 66 and mental health from 60 to 66. A minimal clinically important decreased physical health was observed in 12% of patients aged <65 years, 16% of patients aged 65-79 years, and 22% of patients aged ≥80 years (P = .023). A decreased mental health was observed in 15% of patients aged <65 years, 22% of patients aged 65-79 years, and 24% aged ≥80 years (P = .030). Older age and a greater physical and mental score at baseline were associated with a decreased physical and mental quality of life (P < .001). CONCLUSIONS: Patients surviving surgical aortic valve replacement on average improve in physical and mental quality of life; nonetheless, with increasing age patients are at higher risk of experiencing a deterioration

The Nuclear Protein Sge1 of Fusarium oxysporum Is Required for Parasitic Growth

Dimorphism or morphogenic conversion is exploited by several pathogenic fungi and is required for tissue invasion and/or survival in the host. We have identified a homolog of a master regulator of this morphological switch in the plant pathogenic fungus Fusarium oxysporum f. sp. lycopersici. This non-dimorphic fungus causes vascular wilt disease in tomato by penetrating the plant roots and colonizing the vascular tissue. Gene knock-out and complementation studies established that the gene for this putative regulator, SGE1 (SIX Gene Expression 1), is essential for pathogenicity. In addition, microscopic analysis using fluorescent proteins revealed that Sge1 is localized in the nucleus, is not required for root colonization and penetration, but is required for parasitic growth. Furthermore, Sge1 is required for expression of genes encoding effectors that are secreted during infection. We propose that Sge1 is required in F. oxysporum and other non-dimorphic (plant) pathogenic fungi for parasitic growth

Characterisation of pathogen-specific regions and novel effector candidates in Fusarium oxysporum f. sp. cepae

A reference-quality assembly of Fusarium oxysporum f. sp. cepae (Foc), the causative agent of onion basal rot has been generated along with genomes of additional pathogenic and non-pathogenic isolates of onion. Phylogenetic analysis confirmed a single origin of the Foc pathogenic lineage. Genome alignments with other F. oxysporum ff. spp. and non pathogens revealed high levels of syntenic conservation of core chromosomes but little synteny between lineage specific (LS) chromosomes. Four LS contigs in Foc totaling 3.9 Mb were designated as pathogen-specific (PS). A two-fold increase in segmental duplication events was observed between LS regions of the genome compared to within core regions or from LS regions to the core. RNA-seq expression studies identified candidate effectors expressed in planta, consisting of both known effector homologs and novel candidates. FTF1 and a subset of other transcription factors implicated in regulation of effector expression were found to be expressed in planta