Mogens Lytken Larsen

The role of personality variables and social support in distress and perceived health in patients following myocardial infarction

OBJECTIVESn(1) To investigate whether patients with low versus high social support and satisfaction with support report less distress and health complaints following a first myocardial infarction (MI). (2) To examine whether personality traits mediate social support and its effect on distress and health complaints.nnnMETHODSnA questionnaire was distributed to 112 consecutive patients with a first MI 4-6 weeks postinfarction. Objective clinical measures were obtained from the patients medical records.nnnRESULTSnPatients with low social support were at increased risk of depression and posttraumatic stress disorder (PTSD). Patients less satisfied with support were at increased risk of anxiety, depression, PTSD, and reported more health complaints. Generally, larger effect sizes were found for satisfaction with support compared with social support per se in relation to distress and health complaints. Neuroticism was identified as an independent predictor of all types of distress and health complaints when including both traits and social support variables in multivariable analyses, adjusted for demographic and clinical variables. Satisfaction with support only remained an independent predictor of depression.nnnCONCLUSIONnThese results suggest that personality traits may mediate social support and its effect on distress and health complaints. Hence, it may be important to include personality variables when investigating social support in relation to distress and health. In clinical practice, screening for particular personality traits could identify patients at risk of distress and recurrent cardiac events.

Posttraumatic stress disorder in first-time myocardial infarction patients.

OBJECTIVESnThe objectives of this study were to investigate the prevalence of posttraumatic stress disorder in patients with a first myocardial infarction compared with a random sample of healthy controls and to determine variables associated with the disorder.nnnDESIGNnA questionnaire was distributed to 112 consecutive patients 4 to 6 weeks after infarction and to 115 healthy controls selected randomly from the general population. Objective clinical measures were obtained from the patients medical records.nnnRESULTSnTwenty-five (22%) patients qualified for a diagnosis of posttraumatic stress disorder (PTSD) compared with 8 (7%) controls with patients being more than a three-fold (OR: 3.84; 95% CI: 1.65 to 8.94) risk of having the disorder. When adjusting for other variables, the risk was reduced to above a two-fold risk (OR: 2.71; 95% CI: 0.99-7.41). In patients and controls, depression and neuroticism were associated with a diagnosis of PTSD adjusting for other variables. In patients, anxiety was associated with a diagnosis of PTSD adjusting for other variables. Left ventricular ejection fraction and symptoms of angina pectoris were not related to a diagnosis of PTSD in the patient group.nnnCONCLUSIONSnGiven that previous research has shown that persons with PTSD are at increased risk of cardiovascular diseases, cardiac patients with the disorder may be at a higher risk of recurrent cardiac events. Although longitudinal studies are needed to confirm such a relationship, this disorder should not be overlooked because of its potential role in reinfarctions and mortality.

A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets : The Treat-to-Target (3T) Study

BACKGROUNDnGuidelines for the prevention of coronary heart disease call for low-density lipoprotein cholesterol (LDL-C) reduction as the primary target of treatment and reduction of triglycerides (TG) as an additional target.nnnOBJECTIVEnThe purpose of this study was to investigate the ability of atorvastatin and simvastatin to reduce LDL-C and TG concentrations and to meet 3 target lipid levels: LDL-C <or=2.6 mmol/L; TG <or=1.5 mmol/L; and both LDL-C <or=2.6 mmol/L and TG <or=1.5 mmol/L.nnnMETHODSnThe Treat-to-Target (3T) Study was a 52-week, multicenter, randomized, parallel-group study. Using the double-blind, double-dummy technique, adult patients aged 35 to 75 years with cardiovascular disease and dyslipidemia, defined as LDL-C concentration >or=4.0 mmol/L (>or=155 mg/dL), were randomized in a 1:1 ratio to receive once-daily oral treatment with 20 mg atorvastatin or 20 mg simvastatin. Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National Cholesterol Education Program level of LDL-C (<or=2.6 mmol/L [100 mg/dL]) was not reached at 8 weeks.nnnRESULTSnThe intent-to-treat analysis included 552 patients (418 men, 134 women) randomized to receive atorvastatin and 535 (404 men, 131 women) randomized to receive simvastatin. The number of patients enrolled in the study allowed the evaluation fo the drugs effects on TG. Patient demogrpahic characteristics were similar for the 2 treatment groups, and there were no differences in baseline lipid values. Compared with simvastatin, atorvastatin produced significantly greater reductions in LDL-C (8 weeks: -46% vs -40%, P < 0.001; 52 weeks: -49% vs -44%, P < 0.001) and in TG (8 weeks: -23% vs -14%, P < 0.001; 52 weeks: -24% vs -16%, P < 0.001). Compared with simvastatin-treated patients, a significantly greater number of atorvastatin-treated patients reached the LDL-C target after 8 weeks (45% vs 24%; P < 0.001). Fewer atorvastatin patients needed to have their dose doubled; nevertheless more atorvastatin patients reached the LDL-C target after 52 weeks (61% vs 41%; P < 0.001). Both statins were well tolerated. Muscular symptoms occurred in 12 patients (2.2%) in the atorvastatin group and in 13 patients (2.4%) in the simvastatin group.nnnCONCLUSIONSnAtorvastatin 20 or 40 mg/d for up to 1 year of treatment was significantly more effective than simvastatin 20 or 40 mg/d in reducing LDL-C and TG levels and at achieving recommended lipid targets in this selected patient population with cardiovascular disease and dyslipidemia. Both statis were well tolerated.

Detection of large deletions in the LDL receptor gene with quantitative PCR methods

BackgroundFamilial Hypercholesterolemia (FH) is a common genetic disease and at the molecular level most often due to mutations in the LDL receptor gene. In genetically heterogeneous populations, major structural rearrangements account for about 5% of patients with LDL receptor gene mutations.MethodsIn this study we tested the ability of two different quantitative PCR methods, i.e. Real-Time PCR and Multiplex Ligation-Dependent Probe Amplification (MLPA), to detect deletions in the LDL receptor gene. We also reassessed the contribution of major structural rearrangements to the mutational spectrum of the LDL receptor gene in Denmark.ResultsWith both methods it was possible to discriminate between one and two copies of the LDL receptor gene exon 5, but the MLPA method was cheaper, and it was far more accurate and precise than Real-Time PCR. In five of 318 patients with an FH phenotype, MLPA analysis revealed five different deletions in the LDL receptor gene.ConclusionThe MLPA method was accurate, precise and at the same time effective in screening a large number of FH patients for large deletions in the LDL receptor gene.

Genomic characterization of five deletions in the LDL receptor gene in Danish Familial Hypercholesterolemic subjects

BackgroundFamilial Hypercholesterolemia is a common autosomal dominantly inherited disease that is most frequently caused by mutations in the gene encoding the receptor for low density lipoproteins (LDLR). Deletions and other major structural rearrangements of the LDLR gene account for approximately 5% of the mutations in many populations.MethodsFive genomic deletions in the LDLR gene were characterized by amplification of mutated alleles and sequencing to identify genomic breakpoints. A diagnostic assay based on duplex PCR for the exon 7 – 8 deletion was developed to discriminate between heterozygotes and normals, and bioinformatic analyses were used to identify interspersed repeats flanking the deletions.ResultsIn one case 15 bp had been inserted at the site of the deleted DNA, and, in all five cases, Alu elements flanked the sites where deletions had occurred. An assay developed to discriminate the wildtype and the deletion allele in a simple duplex PCR detected three FH patients as heterozygotes, and two individuals with normal lipid values were detected as normal homozygotes.ConclusionThe identification of the breakpoints should make it possible to develop specific tests for these mutations, and the data provide further evidence for the role of Alu repeats in intragenic deletions.