Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. METHODS Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. RESULTS Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). CONCLUSION Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during childhood.Part of the studies were financed by grants from the Swedish Research Council and from the King Gustaf V and Queen Victoria Research Fund and by grants from Grupos de Investigacion y Desarrollo Tecnologico de la Junta de Andalucia (Grupo consolidado CTS- 159).Ye

Quadriceps force generation in patients with osteoarthritis of the knee and asymptomatic participants during patellar tendon reflex reactions: an exploratory cross-sectional study

BACKGROUND: It has been postulated that muscle contraction is slower in patients with osteoarthritis of the knee than asymptomatic individuals, a factor that could theoretically impair joint protection mechanisms. This study investigated whether patients with osteoarthritis of the knee took longer than asymptomatic participants to generate force during reflex quadriceps muscle contraction. This was an exploratory study to inform sample size for future studies. METHODS: An exploratory observational cross sectional study was carried out. Two subject groups were tested, asymptomatic participants (n = 17), mean (SD) 56.7 (8.6) years, and patients with osteoarthritis of the knee, diagnosed by an orthopaedic surgeon, (n = 16), age 65.9 (7.8) years. Patellar tendon reflex responses were elicited from participants and measured with a load cell. Force latency, contraction time, and force of the reflex response were determined from digitally stored data. The Mann-Whitney U test was used for the between group comparisons in these variables. Bland and Altman within-subject standard deviation values were calculated to evaluate the measurement error or precision of force latency and contraction time. RESULTS: No significant differences were found between the groups for force latency (p = 0.47), contraction time (p = 0.91), or force (p = 0.72). The two standard deviation measurement error values for force latency were 27.9 ms for asymptomatic participants and 16.4 ms for OA knee patients. For contraction time, these values were 29.3 ms for asymptomatic participants and 28.1 ms for OA knee patients. Post hoc calculations revealed that the study was adequately powered (80%) to detect a difference between the groups of 30 ms in force latency. However it was inadequately powered (59%) to detect this same difference in contraction time, and 28 participants would be required in each group to reach 80% power. CONCLUSION: Patients with osteoarthritis of the knee do not appear to have compromised temporal parameters or magnitude of force generation during patellar tendon reflex reactions when compared to a group of asymptomatic participants. However, these results suggest that larger studies are carried out to investigate this area further

Psychiatric disorders and subsequent risk of cardiovascular disease: a longitudinal matched cohort study across three countries

Background: Several psychiatric disorders have been associated with increased risk of cardiovascular disease (CVD), however, the role of familial factors and the main disease trajectories remain unknown. Methods: In this longitudinal cohort study, we identified a cohort of 900,240 patients newly diagnosed with psychiatric disorders during January 1, 1987 and December 31, 2016, their 1,002,888 unaffected full siblings, and 1:10 age- and sex-matched reference population from nationwide medical records in Sweden, who had no prior diagnosis of CVD at enrolment. We used flexible parametric models to determine the time-varying association between first-onset psychiatric disorders and incident CVD and CVD death, comparing rates of CVD among patients with psychiatric disorders to the rates of unaffected siblings and matched reference population. We also used disease trajectory analysis to identify main disease trajectories linking psychiatric disorders to CVD. Identified associations and disease trajectories of the Swedish cohort were validated in a similar cohort from nationwide medical records in Denmark (N = 875,634 patients, same criteria during January 1, 1969 and December 31, 2016) and in Estonian cohorts from the Estonian Biobank (N = 30,656 patients, same criteria during January 1, 2006 and December 31, 2020), respectively. Findings: During up to 30 years of follow-up of the Swedish cohort, the crude incidence rate of CVD was 9.7, 7.4 and 7.0 per 1000 person-years among patients with psychiatric disorders, their unaffected siblings, and the matched reference population. Compared with their siblings, patients with psychiatric disorders experienced higher rates of CVD during the first year after diagnosis (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.79–1.98) and thereafter (1.37; 95% CI, 1.34–1.39). Similar rate increases were noted when comparing with the matched reference population. These results were replicated in the Danish cohort. We identified several disease trajectories linking psychiatric disorders to CVD in the Swedish cohort, with or without mediating medical conditions, including a direct link between psychiatric disorders and hypertensive disorder, ischemic heart disease, venous thromboembolism, angina pectoris, and stroke. These trajectories were validated in the Estonian Biobank cohort. Interpretation: Independent of familial factors, patients with psychiatric disorders are at an elevated risk of subsequent CVD, particularly during first year after diagnosis. Increased surveillance and treatment of CVDs and CVD risk factors should be considered as an integral part of clinical management, in order to reduce risk of CVD among patients with psychiatric disorders. Funding: This research was supported by EU Horizon 2020 Research and Innovation Action Grant, European Research Council Consolidator grant, Icelandic Research fund, Swedish Research Council, US NIMH, the Outstanding Clinical Discipline Project of Shanghai Pudong, the Fundamental Research Funds for the Central Universities, and the European Union through the European Regional Development Fund; the Research Council of Norway; the South-East Regional Health Authority, the Stiftelsen Kristian Gerhard Jebsen, and the EEA-RO-NO-2018-0535

Relationships of low density lipoprotein subfractions to angiographically defined coronary artery disease in young survivors of myocardial infarction.

Low density lipoprotein (LDL) from 36 young post-infarction patients was separated by isopycnic density gradient ultracentrifugation to determine the relationships of plasma levels and chemical composition of different LDL subfractions to the global severity and rate of progression of coronary atherosclerosis assessed by angiography. There were marked elevations of the cholesterol and triglyceride concentrations in the very low density lipoprotein (VLDL) fraction, whereas the high density lipoprotein (HDL) cholesterol level was reduced in the patients compared with 70 healthy population-based controls. Plasma total LDL cholesterol and triglyceride concentrations were similar. The distribution of apolipoprotein B along the LDL density range, viz. the LDL particle distribution, was displaced towards the dense LDL region among the patients compared with 14 healthy normolipidaemic controls. A preponderance of dense LDL particles was associated with elevated plasma VLDL triglyceride concentration. The patients had significantly higher plasma concentrations of lipid and protein in dense LDL (d greater than 1.040 kg/l), while no group differences were found in the light LDL (d less than 1.040 kg/l). However, there were no percentage compositional differences in the light or dense LDL between patients and controls. Among all constituents of lipoprotein fractions and subfractions determined, only the plasma level of triglycerides in both light and dense LDL correlated significantly with the angiographic estimates of global severity and rate of progression of coronary atherosclerosis, respectively. On a percentage composition basis, both light and dense LDL tended to be richer in triglycerides in the subjects with a more severe coronary artery disease. Neither VLDL or HDL, nor LDL cholesterol were associated with the angiographic scores, the plasma LDL triglyceride concentration or the triglyceride enrichment of LDL. Although there is ample experimental evidence that triglyceride-enriched LDL predisposes to atherosclerosis, the LDL associations with coronary lesion severity and progression observed in the present study might not reflect a causal mechanism, but merely mirror the atherogenicity of disturbances affecting the metabolism of triglyceride-rich lipoproteins. Prospective studies of larger groups of unselected patients are needed to corroborate these findings