Despite documented benefits of lipid-lowering treatment in women, a considerable number are undertreated, and fewer achieve treatment targets vs. men.
Data were combined from 27 double-blind, active ...or placebo-controlled studies that randomized adult hypercholesterolemic patients to statin or statin+ezetimibe. Consistency of treatment effect among men (n = 11,295) and women (n = 10,499) was assessed and percent of men and women was calculated to evaluate the between-treatment ability to achieve specified treatment levels between sexes.
Baseline lipids and hs-CRP were generally higher in women vs. men. Between-treatment differences were significant for both sexes (all p < 0.001 except apolipoprotein A-I in men = 0.0389). Men treated with ezetimibe+statin experienced significantly greater changes in LDL-C (p = 0.0066), non-HDL-C, total cholesterol, triglycerides, HDL-C, apolipoprotein A-I (all p < 0.0001) and apolipoprotein B (p = 0.0055) compared with women treated with ezetimibe+statin. The odds of achieving LDL-C < 100 mg/dL, apolipoprotein B < 90 mg/dL and the dual target LDL-C < 100 mg/dL & apoliprotein B < 90 mg/dL was significantly greater for women vs. men and the odds of achieving hs-CRP < 1 and < 2 mg/L and dual specified levels of LDL-C < 100 mg/dL and hs-CRP < 2 mg/L were significantly greater for men vs. women. Women reported significantly more gall-bladder-related, gastrointestinal-related, and allergic reaction or rash-related adverse events (AEs) vs. men (no differences between treatments). Men reported significantly more CK elevations (no differences between treatments) and hepatitis-related AEs vs. women (significantly more with ezetimibe+simvastatin vs. statin).
These results suggest that small sex-related differences may exist in response to lipid-lowering treatment and achievement of specified lipid and hs-CRP levels, which may have implications when managing hypercholesterolemia in women.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate the efficacy of docosahexaenoic acid (DHA)-enriched oral supplementation in preventing exudative age-related macular degeneration (AMD).
The Nutritional AMD Treatment 2 study was a ...randomized, placebo-controlled, double-blind, parallel, comparative study.
Two hundred sixty-three patients 55 years of age or older and younger than 85 years with early lesions of age-related maculopathy and visual acuity better than 0.4 logarithm of minimum angle of resolution units in the study eye and neovascular AMD in the fellow eye.
Patients were assigned randomly to receive either 840 mg/day DHA and 270 mg/day eicosapentaenoic acid (EPA) from fish oil capsules or the placebo (olive oil capsules) for 3 years.
The primary outcome measure was time to occurrence of choroidal neovascularization (CNV) in the study eye. Secondary outcome measures in the study eye were: incidence of CNV developing in patients, changes in visual acuity, occurrence and progression of drusen, and changes in EPA plus DHA level in red blood cell membrane (RBCM).
Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA group (19.5±10.9 months and 28.4%, respectively) and the placebo group (18.7±10.6 months and 25.6%, respectively). In the DHA group, EPA plus DHA levels increased significantly in RBCM (+70%; P<0.001), suggesting that DHA easily penetrated cells, but this occurred unexpectedly also in the placebo group (+9%; P = 0.007). In the DHA-allocated group, patients steadily achieving the highest tertile of EPA plus DHA levels in RBCM had significantly lower risk (-68%; P = 0.047; hazard ratio, 0.32; 95% confidence interval, 0.10-0.99) of CNV developing over 3 years. No marked changes from baseline in best-corrected visual acuity, drusen progression, or geographic atrophy in the study eye were observed throughout the study in either group.
In patients with unilateral exudative AMD, 3 years of oral DHA-enriched supplementation had the same effect on CNV incidence in the second eye as did the placebo. However, RBCM fatty acid measurements revealed that CNV incidence was significantly reduced in DHA-supplemented patients showing a steadily high EPA plus DHA index over 3 years.
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Familial hypercholesterolemia (FH), a frequent monogenic condition complicated by premature cardiovascular disease, is characterized by high allelic heterogeneity at the low-density lipoprotein ...receptor ( LDLR) locus. Despite more than a decade of genetic testing, knowledge about intronic disease-causing mutations has remained limited because of lack of available genomic sequences. Based on the finding from bioinformatic analysis that Alu repeats represent 85% of LDLR intronic sequences outside exon-intron junctions, we designed a strategy to improve the exploration of genomic regions in the vicinity of exons in 110 FH subjects from an admixed population. In the first group of 42 patients of negative mutation carriers, as previously established by former screening strategies (denaturing gradient gel electrophoresis, DNA sequencing with former primers overlapping splice-sites, Southern Blotting), about half ( n=22) were found to be carriers of at least one heterozygous mutation. Among a second group of 68 newly recruited patients, 27% of mutation carriers ( n=37) had a splicing regulatory mutation. Overall, out of the 54 mutations identified, 13 were intronic, and 18 were novel, out of which nearly half were intronic. Two novel intronic mutations (IVS8-10G-->A within the polypyrimidine tract and IVS7+10G-->A downstream of donor site) might create potential aberrant splice sites according to neural-network computed estimation, contrary to 31 common single nucleotide variations also identified at exon-intron junctions. This new strategy of detecting the most likely disease-causing LDLR mutations outside of Alu-rich genomic regions reveals that intronic mutations may have a greater impact than previously reported on the molecular basis of FH.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We analyzed the effects of a docosahexaenoic acid (DHA) supplementation in patients affected with late onset Stargardt disease (STGD).
DHA (840 mg/day) was given to 20 STGD patients for six months. A ...complete ophthalmologic examination, including best-corrected visual acuity (BCVA) and multifocal electroretinogram (mfERG), was performed at inclusion day 0 (D0) and at month 6 (M6).
Overall, no statistical differences have been observed at M6 vs D0 as regards BCVA and mfERG (P > 0.05). Mild Improvement of BCVA and improvement of mfERG was noted in seven/40 eyes of four/20 patients. In the first patient, the peak of the a wave increased from 66 nV/deg(2) to 75.4 nV/deg(2) in the right eye (RE) and 24.5 nV/deg(2) to 49.1 nV/deg(2) in the left eye (LE). The peak of the b wave improved from 122 nV/deg(2) to 157 nV/deg(2) in the RE, and 102 nV/deg(2) to 149 nV/deg(2) in the LE. In the second patient peaks of the a and b waves respectively increased from 11.8 nV/deg(2) to 72.1 nV/deg(2) and 53 nV/deg(2) to 185 nV/deg(2) in the RE. In the third patient the peak of the a wave increased from 37 nV/deg(2) to 43 nV/deg(2) in the RE, and from 31 nV/deg(2) to 45 nV/deg(2) in the LE; the peak of the b wave improved from 70 nV/deg(2) to 89 nV/deg(2) in the RE, and from 101 nV/deg(2) to 108 nV/deg(2) in the LE. In the fourth patient, the peak of the a wave increased from 39 nV/deg(2) to 42 nV/deg(2) in the RE, and from 40 nV/deg(2) to 43 nV/deg(2) in the LE; the peak of the b wave improved from 86 nV/deg(2) to 94 nV/deg(2) in the RE, and from 87 nV/deg(2) to 107 nV/deg(2) in the LE.
DHA seems to influence some functional parameters in patients affected with STGD. However, no short-term benefit should be expected from DHA supplementation.
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