Current perspectives on statins Maron, D J; Fazio, S; Linton, M F
Circulation,
01/2000, Letnik:
101, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Statins (HMG-CoA reductase inhibitors) are used widely for the treatment of hypercholesterolemia. They inhibit HMG-CoA reductase competitively, reduce LDL levels more than other cholesterol-lowering ...drugs, and lower triglyceride levels in hypertriglyceridemic patients. Statins are well tolerated and have an excellent safety record. Clinical trials in patients with and without coronary heart disease and with and without high cholesterol have demonstrated consistently that statins reduce the relative risk of major coronary events by approximately 30% and produce a greater absolute benefit in patients with higher baseline risk. Proposed mechanisms include favorable effects on plasma lipoproteins, endothelial function, plaque architecture and stability, thrombosis, and inflammation. Mechanisms independent of LDL lowering may play an important role in the clinical benefits conferred by these drugs and may ultimately broaden their indication from lipid-lowering to antiatherogenic agents.
Premature coronary artery disease is a major cause of illness and death in patients with systemic lupus erythematosus, but little is known about the prevalence, extent, and causes of coronary-artery ...atherosclerosis.
We used electron-beam computed tomography to screen for the presence of coronary-artery calcification in 65 patients with systemic lupus erythematosus (mean +/-SD age, 40.3+/-11.6 years) and 69 control subjects (mean age, 42.7+/-12.6 years) with no history of coronary artery disease. When calcification was detected, the extent was measured by means of the Agatston score. The frequency of risk factors for coronary artery disease was compared in patients and controls, and the relation between the patients' clinical characteristics and the presence or absence of coronary-artery calcification was examined.
The two groups were similar with respect to age, race, and sex. Coronary-artery calcification was more frequent in patients with lupus (20 of 65 patients) than in control subjects (6 of 69 subjects) (P=0.002). The mean calcification score was 68.9+/-244.2 in the patients and 8.8+/-41.8 (P<0.001) in controls. Levels of total, high-density lipoprotein, and low-density lipoprotein cholesterol were not elevated in patients with lupus, but levels of triglycerides (P=0.02) and homocysteine (P<0.001) were. Among patients with lupus, measures of disease activity were similar in those with and those without coronary-artery calcification, but those with calcification were more likely to be older (P<0.001) and male (P=0.008).
In patients with systemic lupus erythematosus, the prevalence of coronary-artery atherosclerosis is elevated and the age at onset is reduced. Early detection of atherosclerosis may provide an opportunity for therapeutic intervention.
Purpose
To evaluate whether a protocol for early intervention addressing the psychosocial risk factors for delayed return to work in workers with soft tissue injuries would achieve better long-term ...outcomes than usual (stepped) care.
Methods
The study used a controlled, non-randomised prospective design to compare two case management approaches. For the intervention condition, workers screened within 1–3 weeks of injury as being at high risk of delayed returned to work by the Örebro Musculoskeletal Pain Screening Questionnaire—short version (ÖMPSQ-SF) were offered psychological assessment and a comprehensive protocol to address the identified obstacles for return to work. Similarly identified injured workers in the control condition were managed under usual (stepped) care arrangements.
Results
At 2-year follow-up, the mean lost work days for the Intervention group was less than half that of the usual care group, their claim costs were 30% lower, as was the growth trajectory of their costs after 11 months.
Conclusions
The findings supported the hypothesis that brief psychological risk factor screening, combined with a protocol for active collaboration between key stakeholders to address identified psychological and workplace factors for delayed return to work, can achieve better return on investment than usual (stepped) care.
To establish whether review articles provide consistent conclusions on associations between workplace psychosocial factors and musculoskeletal pain and, if differences exist, to explore whether this ...is related to the methods used.
Reviews, reported up to February 2007, that included consideration of workplace psychosocial factors and upper limb, back or knee pain were identified through searches of multiple databases. The specific work-related psychosocial factors considered were job demands, support, job autonomy and job satisfaction. The conclusions of each review on one or more of the psychosocial/musculoskeletal pain associations were extracted.
15 review articles were identified that considered one or more of the regional pain syndromes included in the study. For back pain, the most consistent conclusions (four reviews positive out of six) were with high job demands and low job satisfaction. The studies of upper limb pain were exclusively related to shoulder and/or neck pain, and the most consistent positive conclusions were with high and low job demands (four reviews positive out of six and two reviews positive out of three, respectively). For knee pain, only a single review was identified. For individual reviews of back and upper limb pain, there were marked differences in the number of associations concluded to be positive between reviews.
The reasons for reviews coming to different conclusions included that they were often evaluating different bodies of evidence (according to their search criteria, the year when the review was conducted, the role that quality assessment played in whether studies contributed to evidence, and the combination of risk factors addressed in individual studies), but more important was whether the review specified explicit criteria for making conclusions on strength of evidence. These conclusions emphasise the importance of developing standardised methods for conducting such evaluations of existing evidence and the importance of new longitudinal studies for clarifying the temporal relationship between psychosocial factors and musculoskeletal pain in the workplace.
Abstract Background and aims Diet may play an important role in the development of hyperuricemia and gout. However, the association between dietary factors and hyperuricemia remains unclear, and few ...studies have investigated direct links between food intake and hyperuricemia. The aim of this study was to investigate associations between high purine-content foods and protein intake with the prevalence of hyperuricemia by using data from a cross-sectional study of 3978 men aged 40–74 yrs living in Shanghai, China. Methods and Results Hyperuricemia was defined as blood uric acid level >7.0 mg/dl. One quarter of this population had hyperuricemia. Dietary information was collected by using a food frequency questionnaire. We collected information on anthropometric measurements and lifestyle factors and other potential confounding factors and disease history via interviews. Total protein consumption was not associated with hyperuricemia. We found a positive association between protein from animal sources and prevalence of hyperuricemia and an inverse association between protein from plant sources and hyperuricemia. However, these associations failed to reach significance in mutually adjusted analysis. Seafood intake was associated with higher prevalence of hyperuricemia. The ORs for quintiles of seafood intake (including fish and shellfish) were 1.00, 1.49, 1.35, 1.34, and 1.56 (p for trend: 0.01). An inverse association approaching significance between soy food consumption and hyperuricemia was observed (ORs: 1.00, 0.90, 0.70, 0.89, and 0.77 for quintiles of intake; p for trend: 0.07). No associations between consumption of purine-rich vegetables or meat and prevalence of hyperuricemia were observed. Conclusions Our data suggest a direct association between seafood consumption and hyperuricemia and an inverse association between consumption of soy food and hyperuricemia among middle-aged, Chinese men.
Purpose
(1) to examine the ability of the Örebro Musculoskeletal Pain Screening Questionnaire-short version (ÖMPSQ-SF) to predict time to return to pre-injury work duties (PID) following a ...work-related soft tissue injury (regardless of body location); and (2) to examine the appropriateness of 50/100 as a suitable cut-off score for case identification.
Methods
Injured workers (IW) from six public hospitals in Sydney, Australia, who had taken medically-sanctioned time off work due to their injury, were recruited by insurance case managers within 5–15 days of their injury. Eligible participants (N = 213 in total) were administered the ÖMPSQ-SF over the telephone by the case manager. For objective (1) Cox proportional hazards regression analysis was used to predict days to return to PID using the ÖMPSQ-SF. For objective (2) receiver operator characteristic (ROC) analysis was used to determine the ÖMPSQ-SF total score that optimises sensitivity and specificity in detecting whether or not participants had returned to PID within 2–7 weeks.
Results
The total ÖMPSQ-SF score significantly predicted number of days to return to PID, such that for every 1-point increase in the total ÖMPSQ-SF score the predicted chance of returning to work reduced by 4% (i.e., hazard ratio = 0.96),
p
< 0.001. Sensitivity and specificity for the ROC analysis comparing ÖMPSQ-SF total score to return to PID within 2–7 weeks suggested 48 as the optimal cut off (sensitivity = 0.65, specificity = 0.79).
Conclusion
The results provide strong support for the use of the ÖMPSQ-SF in an applied setting for identifying those IW likely to have delayed RTW when administered within 15 days of the injury. While a score of 48/100 was the optimal cut point for sensitivity and specificity, pragmatically, 50/100 should be acceptable as a cut-off in future studies of this type.
P‐glycoprotein (P‐gp) is an ABC (ATP‐binding cassette) transporter, which hydrolyses ATP and extrudes cytotoxic drugs from mammalian cells. P‐gp consists of two transmembrane domains (TMDs) that span ...the membrane multiple times, and two cytoplasmic nucleotide‐binding domains (NBDs). We have determined projection structures of P‐gp trapped at different steps of the transport cycle and correlated these structures with function. In the absence of nucleotide, an ∼10 Å resolution structure was determined by electron cryo‐microscopy of two‐dimensional crystals. The TMDs form a chamber within the membrane that appears to be open to the extracellular milieu, and may also be accessible from the lipid phase at the interfaces between the two TMDs. Nucleotide binding causes a repacking of the TMDs and reduction in drug binding affinity. Thus, ATP binding, not hydrolysis, drives the major conformational change associated with solute translocation. A third distinct conformation of the protein was observed in the post‐hydrolytic transition state prior to release of ADP/Pi. Biochemical data suggest that these rearrangements may involve rotation of transmembrane α‐helices. A mechanism for transport is suggested.
The adipocyte fatty-acid-binding protein, aP2, has an important role in regulating systemic insulin resistance and lipid metabolism. Here we demonstrate that aP2 is also expressed in macrophages, has ...a significant role in their biological responses and contributes to the development of atherosclerosis. Apolipoprotein E (ApoE)-deficient mice also deficient for aP2 showed protection from atherosclerosis in the absence of significant differences in serum lipids or insulin sensitivity. aP2-deficient macrophages showed alterations in inflammatory cytokine production and a reduced ability to accumulate cholesterol esters when exposed to modified lipoproteins. Apoe-/- mice with Ap2+/+ adipocytes and Ap2-/- macrophages generated by bone-marrow transplantation showed a comparable reduction in atherosclerotic lesions to those with total aP2 deficiency, indicating an independent role for macrophage aP2 in atherogenesis. Through its distinct actions in adipocytes and macrophages, aP2 provides a link between features of the metabolic syndrome and could be a new therapeutic target for the prevention of atherosclerosis.
The majority of apoptotic cells in atherosclerotic lesions are macrophages. However, the pathogenic role of macrophage apoptosis in the development of atherosclerosis remains unclear. Elevated ...expression of Bax, one of the pivotal proapoptotic proteins of the Bcl-2 family, has been found in human atherosclerotic plaques. Activation of Bax also occurs in free cholesterol-loaded and oxysterol-treated mouse macrophages. In this study, we examined the effect of Bax deficiency in bone marrow-derived leukocytes on the development of atherosclerosis in low-density lipoprotein receptor-null (LDLR-/-) mice.
Fourteen 8-week-old male LDLR-/- mice were lethally irradiated and reconstituted with either wild-type (WT) C57BL6 or Bax-null (Bax-/-) bone marrow. Three weeks later, the mice were challenged with a Western diet for 10 weeks. No differences were found in the plasma cholesterol level between the WT and Bax-/- group. However, quantitation of cross sections from proximal aorta revealed a 49.2% increase (P=0.0259) in the mean lesion area of the Bax-/- group compared with the WT group. A 53% decrease in apoptotic macrophages in the Bax-/- group was found by TUNEL staining (P<0.05).
The reduction of apoptotic activity in macrophages stimulates atherosclerosis in LDLR-/- mice, which is consistent with the hypothesis that macrophage apoptosis suppresses the development of atherosclerosis.
To explore self-inflicted retinal burns from laser pointers in children.
Literature review of laser pointer retinal injuries in childhood and online survey of UK Consultant Ophthalmologists. A cohort ...of local children with self-inflicted injury is described. The matter is topical. We review progress in recent legislation and policy change in the UK.
Four of 77 case reports of laser burns in childhood analysed reported psychological or behavioural issues. Three of four children in our cohort had such issues. Delay in diagnosis occurred in two of our patients. Structural retinal damage persisted for over 12 months in all four children (seven eyes). Our survey of UK ophthalmologists found 159 cases of injury (85% male), 80% under 20 years of age. The majority of the laser pointers were purchased online. Many patients (36%) suffered moderate vision loss (6/18 to 6/60 Snellen), while 17% (at least 11 patients) suffered severe vision loss (<6/60 Snellen).
We highlight the risk of macular damage and vision loss from handheld lasers specifically in children with behavioural, learning or mental health issues. The diagnosis may be difficult or delayed in such children. In children with uncertain macular changes, ophthalmologists should explore the history for possible instances of exposure to handheld lasers pointers. Regulatory authorities and manufacturers of handheld lasers need to be aware of the risk to children. Furthermore, there is a need to better inform parents, carers and teachers of the risk of ocular self-injury from such lasers pointers.
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