Variant ASGR1 Associated with a Reduced Risk of Coronary Artery Disease.

BACKGROUND: Several sequence variants are known to have effects on serum levels of non-high-density lipoprotein (HDL) cholesterol that alter the risk of coronary artery disease. METHODS: We sequenced the genomes of 2636 Icelanders and found variants that we then imputed into the genomes of approximately 398,000 Icelanders. We tested for association between these imputed variants and non-HDL cholesterol levels in 119,146 samples. We then performed replication testing in two populations of European descent. We assessed the effects of an implicated loss-of-function variant on the risk of coronary artery disease in 42,524 case patients and 249,414 controls from five European ancestry populations. An augmented set of genomes was screened for additional loss-of-function variants in a target gene. We evaluated the effect of an implicated variant on protein stability. RESULTS: We found a rare noncoding 12-base-pair (bp) deletion (del12) in intron 4 of ASGR1, which encodes a subunit of the asialoglycoprotein receptor, a lectin that plays a role in the homeostasis of circulating glycoproteins. The del12 mutation activates a cryptic splice site, leading to a frameshift mutation and a premature stop codon that renders a truncated protein prone to degradation. Heterozygous carriers of the mutation (1 in 120 persons in our study population) had a lower level of non-HDL cholesterol than noncarriers, a difference of 15.3 mg per deciliter (0.40 mmol per liter) (P=1.0×10(-16)), and a lower risk of coronary artery disease (by 34%; 95% confidence interval, 21 to 45; P=4.0×10(-6)). In a larger set of sequenced samples from Icelanders, we found another loss-of-function ASGR1 variant (p.W158X, carried by 1 in 1850 persons) that was also associated with lower levels of non-HDL cholesterol (P=1.8×10(-3)). CONCLUSIONS: ASGR1 haploinsufficiency was associated with reduced levels of non-HDL cholesterol and a reduced risk of coronary artery disease. (Funded by the National Institutes of Health and others.).

Prognostic role of genetic polymorphisms of the interleukin-6 signaling pathway in patients with severe heart failure.

Heart failure (HF) is associated with perturbations of the interleukin-6 (IL-6) signaling pathway. A total of 559 Danish subjects with severe chronic HF enrolled in the previously reported Echocardiography and Heart Outcome Study were genotyped for three SNPs in IL6, nine in the IL-6 receptor gene (IL6R), and two in the IL-6 signal transducer gene (IL6ST). After a mean follow-up of 5.0 years, 5 SNPs in IL6R introns (rs12083537, rs6684439, rs4845622, rs4537545, and rs7529229) and a SNP in the IL6R coding region (rs2228145, also known as Asp358Ala) were associated with adverse outcomes, e.g., hazard ratios (HRs) for cardiovascular death and all-cause death 1.38 (CI: 1.09-1.76; P = 0.008) and 1.37 (CI: 1.10-1.70; P = 0.004) for rs6684439 heterozygotes, and 1.39 (CI: 1.09-1.77; P = 0.007) and 1.37 (CI: 1.10-1.70; P = 0.005) for rs4845622 heterozygotes, respectively. We conclude that SNPs in the IL-6 signaling pathway may be independent predictors of fatal outcomes in patients with severe HF.

Imiquimod-Induced Psoriasis-Like Skin Lesions Do Not Accelerate Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice.

Psoriasis is a chronic inflammatory skin disorder associated with several comorbidities, including atherosclerosis. Disease mechanisms that may affect both psoriasis and atherosclerosis include activation of T helper 1 and T helper 17 cells. Imiquimod application is an established mouse model of psoriasis-like skin inflammation. The cardiac glycoside digoxin inhibits the master transcription factor of T helper 17 differentiation, retinoid acid receptor-related orphan nuclear receptor γt, and attenuates IL-17-dependent pathologies in mice. We investigated whether cyclic imiquimod-induced psoriasis-like skin inflammation affects atherosclerosis in low-density lipoprotein receptor-deficient mice and whether digoxin modifies either disease. Topical imiquimod application increased ear thickness, keratinocyte proliferation, and accumulation of CD3+ T cells in the skin of low-density lipoprotein receptor-deficient mice. Also, imiquimod affected the mice systemically with induction of splenomegaly as well as increased plasma levels of IL-17A and serum amyloid A. Overall, imiquimod reduced atherosclerosis in the aortic arch en face, but it did not affect atherosclerosis in the aortic root. Digoxin significantly reduced the imiquimod-induced ear thickening, had divergent effects on imiquimod-induced systemic inflammation, and did not affect atherosclerosis. In conclusion, cyclic imiquimod applications can be used for long-term induction of psoriasis-like skin lesions, but they attenuate atherosclerosis in low-density lipoprotein-deficient mice. In this model, digoxin reduces skin inflammation, but it has no effect on atherosclerosis.

Validation of the HCM Risk-SCD model in patients with hypertrophic cardiomyopathy following alcohol septal ablation.

Aims: The HCM Risk-SCD model for prediction of sudden cardiac death (SCD) in hypertrophic cardiomyopathy recommended by the 2014 European Society of Cardiology (ESC) guidelines has not been validated after septal reduction therapy. The aim of this study was to validate the HCM Risk-SCD model in patients undergoing alcohol septal ablation (ASA) and to compare its performance to previous models. Methods and result: A total of 844 ASA patients without prior SCD event were included. The primary endpoint was a composite of SCD and appropriate implantable cardioverter defibrillator (ICD) therapy, identical to the HCM Risk-SCD endpoint. A distinction between periprocedural (≤30 days) and long-term (>30 days) SCD was made to discern procedure-related adverse arrhythmic events caused by the ASA-induced myocardial infarction from long-term SCD risk. Twenty patients reached the SCD endpoint within the first 30 days. During a follow-up of 6.5 ± 4.2 years, another 46 patients reached the SCD endpoint. The predicted 5-year SCD risk according to the HCM Risk-SCD model was 5.1%, and the observed 5-year SCD risk was 4.0%. The C-statistics for the use of the HCM Risk-SCD model was 0.61 (P = 0.02), the C-statistics for the use of the 2003 American College of Cardiology/ESC guidelines was 0.59 (P = 0.051), and the C-statistic for the use of the 2011 American College of Cardiology Foundation/American Heart Association guidelines was 0.58 (P = 0.054). Maximal left ventricular wall thickness, syncope after ASA, and fulfilling the 2014 ESC recommendations for primary ICD implantation according to the HCM Risk-SCD model, respectively, predicted SCD during long-term follow-up. Conclusion: The HCM Risk-SCD model can be used for SCD prediction in patients undergoing ASA.

Effects of recreational football on women's fitness and health: adaptations and mechanisms.

The review describes the fitness and health effects of recreational football in women aged 18-65 years. The review documents that 2 × 1 h of recreational football training for 12-16 weeks causes marked improvements in maximal oxygen uptake (5-15%) and myocardial function in women. Moreover, mean arterial blood pressure was shown to decrease by 2-5 mmHg in normotensive women and 6-8 mmHg in hypertensive women. This review also show that short-term (< 4 months) and medium-term (4-16 months) recreational football training has major beneficial impact on metabolic health profile in women, with fat losses of 1-3 kg and improvements in blood lipid profile. Lastly, 2 × 1 h per week of recreational football training for women elevates lower extremity bone mineralisation by 1-5% and whole-body bone mineralization by 1-2% within 4-12-month interventions. These training adaptations are related to the high heart rates, high number of fast runs, and multiple changes of direction and speed occurring during recreational football training for untrained women. In conclusion, regular small-sided football training for women is an intense and versatile type of training that combines elements of high-intensity interval training (HIIT), endurance training and strength training, thereby providing optimal stimuli for cardiovascular, metabolic and musculoskeletal fitness. Recreational football, therefore, seems to be an effective tool for prevention and treatment of lifestyle diseases in young and middle-aged women, including hypertension, type 2 diabetes and osteopenia. Future research should elucidate effects of football training for elderly women, and as treatment and rehabilitation of breast cancer patients and other women patient groups.

Coronary microvascular dysfunction and myocardial contractile reserve in women with angina and no obstructive coronary artery disease.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a potential cause of myocardial ischemia and may affect myocardial function at rest and during stress. We investigated whether CMD was associated with left ventricular diastolic and systolic function at rest and during pharmacologically induced hyperemic stress. METHODS: In a prospective cohort study, we included 963 women with angina, left ventricular ejection fraction (LVEF) >45%, and an invasive coronary angiogram without significant stenosis (<50%). Parameters of left ventricular diastolic function, LVEF, speckle tracking-derived global longitudinal strain (GLS), and coronary flow velocity reserve (CFVR) were assessed by transthoracic echocardiography at rest and during dipyridamole stress. The GLS and LVEF reserves were defined as the absolute increases in GLS and LVEF during stress. RESULTS: Coronary flow velocity reserve (CFVR) was measured in 919 women of whom 26% had CMD (defined as CFVR < 2). Coronary microvascular dysfunction (CMD) was associated with higher age and a higher resting heart rate. Women with CMD had a reduced GLS reserve (P = .005), while we found no association between CFVR and LVEF at rest, GLS at rest, or the LVEF reserve, respectively. Global longitudinal strain (GLS) reserve remained associated with CFVR (P = .002) in a multivariable regression analysis adjusted for age, hemodynamic variables, and GLS at rest. In age-adjusted analysis, women with low CFVR had no signs of left ventricular diastolic dysfunction measured by echocardiography at rest. CONCLUSION: The GLS reserve was significantly lower in women with CMD. The mechanisms underlying the association between CMD and GLS reserve warrant further study.

Ventricular repolarization alterations in women with angina pectoris and suspected coronary microvascular dysfunction.

OBJECTIVES: CMD could be the explanation of angina pectoris with no obstructive CAD and may cause ventricular repolarization changes. We compared T-wave morphology and QTc interval in women with angina pectoris with a control group as well as the associations with CMD. METHODS: Women with angina pectoris and no obstructive coronary artery disease (n=138) and age-matched controls were compared in regard to QTc interval and morphology combination score (MCS) based on T-wave asymmetry, flatness and presence of T-wave notch. CMD was assessed as a coronary flow velocity reserve (CFVR) by transthoracic echocardiography. RESULTS: Women with angina pectoris had significantly longer QTc intervals (429±20ms) and increased MCS (IQR) (0.73 [0.64-0.80]) compared with the controls (419±20ms) and (0.63 [(0.53-0.73]), respectively (both p<0.001). CFVR was associated with longer QTc interval (p=0.02), but the association was attenuated after multivariable adjustment (p=0.08). CONCLUSION: This study suggests that women with angina pectoris have alterations in T-wave morphology as well as longer QTc interval compared with a reference population. CMD might be an explanation.

Patients with rosacea have increased risk of dementia.

OBJECTIVE: Rosacea is a common chronic inflammatory skin disorder where upregulation of matrix metalloproteinases (MMPs) and antimicrobial peptides (AMPs) is observed. Notably, inflammation, MMPs, and AMPs are also involved in the etiopathogenesis of neurodegenerative disorders including certain forms of dementia such as Alzheimer disease (AD). Based on several clinical observations, we investigated the association between rosacea and dementia, including AD in Danish registers. METHODS: All Danish citizens aged ≥18 years between January 1, 1997 and December 31, 2012 were linked at the individual level through administrative registers. Cox regression was used to calculate unadjusted and adjusted hazard ratios (HRs). RESULTS: The study comprised a total of 5,591,718 individuals, including 82,439 patients with rosacea. A total of 99,040 individuals developed dementia (any form) in the study period, of whom 29,193 were diagnosed with AD. The adjusted HRs of dementia and AD were 1.07 (95% confidence interval [CI] = 1.01-1.14), and 1.25 (95% CI = 1.14-1.37), respectively, in patients with rosacea. Stratified by sex, the HRs of AD were 1.28 (95% CI = 1.15-1.45) and 1.16 (95% CI = 1.00-1.35) in women and men, respectively. When results were stratified by age at study entry, the risk of AD was only significantly increased in individuals ≥60 years old (adjusted HR = 1.20, 95% CI = 1.08-1.32). When analyses were limited to patients with a hospital dermatologist diagnosis of rosacea only, the adjusted HRs of dementia and AD were 1.42 (95% CI = 1.17-1.72) and 1.92 (95% CI = 1.44-2.58), respectively. INTERPRETATION: Rosacea is significantly associated with dementia, particularly AD. Increased focus on symptoms of cognitive dysfunction in older patients with rosacea may be relevant. Ann Neurol 2016;79:921-928.

Erectile Dysfunction in Male Adults With Atopic Dermatitis and Psoriasis.

INTRODUCTION: Patients with psoriasis have increased risk of cardiovascular disease, but data on atopic dermatitis (AD) are less clear-cut. However, it is well-established that erectile dysfunction (ED) can serve as a risk marker for coronary disease. AIM: To investigate the incidence, prevalence, and risk of ED in men with psoriasis and AD. METHODS: The sample included all Danish men at least 30 years old. In patients with AD and psoriasis, we determined disease severity based on use of systemic therapy. We performed a cross-sectional study (January 1, 2008) using logistic regression to estimate the prevalence and odds ratio of ED. Moreover, in a cohort study design, patients were followed from January 1, 2008 through December 31, 2012, and Cox regression models were used to estimate adjusted hazard ratios of new-onset ED. Models were adjusted for potential confounding factors, including age, socioeconomic status, health care consumption, smoking, alcohol abuse, diabetes, and cholesterol-lowering drug use. MAIN OUTCOME MEASURES: The outcome was initiation of pharmacotherapy used for treatment of ED. RESULTS: The sample consisted of 1,756,679 Danish men (age range = 30-100 years), of which 2,373 and 26,536 had adult AD (mild = 1,072; severe = 1,301) and psoriasis (mild = 21,775; severe = 4,761), respectively. Mean ages (SDs) were 53.0 (14.6), 46.7 (12.0), and 56.3 (13.8) years for the general population, patients with AD, and patients with psoriasis, respectively. Prevalences of ED were 8.7%, 6.7%, and 12.8% for the general population, patients with AD, and patients with psoriasis, respectively. Adjusted odds ratios (logistic regression) of ED were decreased in patients with AD (0.68; 0.57-0.80) but increased in those with psoriasis (1.15; 1.11-1.20). Adjusted odds ratios for mild and severe AD were 0.63 (0.48-0.82) and 0.72 (0.58-0.88), respectively, and those for psoriasis these were 1.16 (1.11-1.21) and 1.13 (1.03-1.23). Adjusted hazard ratios (Cox regression) were 0.92 (0.76-1.11) for AD and 1.14 (1.08-1.20) for psoriasis. The ED risk was not increased in men with mild AD (0.85; 0.63-1.14) or severe AD (0.97; 0.76-1.24) but was significantly increased in men with mild psoriasis (1.13; 1.09-1.20) and severe psoriasis (1.17; 1.04-1.32). CONCLUSION: We found an increased prevalence and risk of ED in men with psoriasis, whereas the risk was comparable to (and even slightly lower than) the general population for men with AD. Egeberg A, Hansen PR, Gislason GH, et al. Erectile Dysfunction in Male Adults With Atopic Dermatitis and Psoriasis. J Sex Med 2017;14:380-386.

Physical Fitness and Body Composition in 8-10-Year-Old Danish Children Are Associated With Sports Club Participation.

Larsen, MN, Nielsen, CM, Ørntoft, CØ, Randers, M, Manniche, V, Hansen, L, Hansen, PR, Bangsbo, J, and Krustrup, P. Physical fitness and body composition in 8-10-year-old Danish children are associated with sports club participation. J Strength Cond Res 31(12): 3425-3434, 2017-We investigated whether physical fitness and body composition in 8-10-year-old Danish children are associated with sports club participation. The study included 423 schoolchildren, comprising 209 girls and 214 boys, of whom 67 and 74%, respectively, were active in sports clubs. Yo-Yo intermittent recovery level 1 for children (YYIR1C), balance, jump and coordination tests, together with dual-energy X-ray absorptiometry, were used to determine exercise capacity and body composition. Children active in sports clubs had better (p < 0.05) YYIR1C (33%, 767 ± 26 vs. 575 ± 29 m), 20-m sprint (3%, 4.33 ± 0.03 vs. 4.48 ± 0.04 seconds), coordination (6%, 68 ± 1 vs. 72 ± 1 second), and balance test performances (9%, 19.3 ± 0.5 vs. 21.2 ± 0.7 falls·min) and lower fat mass index (16%, 3.8 ± 0.1 vs. 4.5 ± 0.2 kg[fat]·m) than children not active in sports clubs. Ball game players had better (p < 0.05) YYIR1C (38%, 925 ± 39 vs. 671 ± 28 m), 20-m sprint (4%, 4.25 ± 0.03 vs. 4.42 ± 0.04 seconds), and coordination test performances (5%, 65 ± 1 vs. 69 ± 1 second), along with higher (p < 0.05) lean body mass (5%, 24.00 ± 0.22 vs. 22.83 ± 0.25 kg) and whole-body BMD (2%, 0.90 ± < 0.01 vs. 0.88 ± <0.01 g·cm) compared with children active in other sports. The study showed that 8[FIGURE DASH]10-year-old Danish children engaged in sports-club activity, especially ball game players, have better exercise capacity and superior body composition compared with children not active in sports clubs.

Prognostic impact of carboxylesterase 1 gene variants in patients with congestive heart failure treated with angiotensin-converting enzyme inhibitors.

OBJECTIVE: Most angiotensin-converting enzyme inhibitors (ACEIs) are prodrugs activated by carboxylesterase 1 (CES1). We investigated the prognostic importance of CES1 gene (CES1) copy number variation and the rs3815583 single-nucleotide polymorphism in CES1 among ACEI-treated patients with congestive heart failure (CHF). METHODS: Danish patients with chronic CHF enrolled in the previously reported Echocardiography and Heart Outcome Study were categorized according to their CES1 variants and followed up for up to 10 years. Risk for cardiovascular death and all-cause death was modeled by Cox proportional hazard analyses. RESULTS: A total of 491 ACEI-treated patients were included in the analyses. After a mean follow-up of 5.5 years, we found no difference in the risk for cardiovascular death and all-cause death between patients having three [hazard ratios (HRs) 1.06 (95% confidence interval (CI) 0.77-1.45) and 1.16 (95% CI 0.88-1.52)] or four [HRs 0.88 (95% CI 0.39-2.01) and 1.37 (95% CI 0.74-2.54)] CES1 copies and those with two copies, respectively. Similarly, no difference in the risk for cardiovascular and all-cause death was found for patients heterozygous [HRs 0.91 (95% CI 0.70-1.19) and 0.88 (95% CI 0.69-1.12)] or homozygous [HRs 0.58 (95% CI 0.30-1.15) and 0.82 (95% CI 0.48-1.39)] for the rs3815583 minor allele versus patients homozygous for the major allele. The active promoter of CES1A2 and the rs71647871 single-nucleotide polymorphism minor allele were detected at very low frequencies. CONCLUSION: This study did not support the use of CES1 copy number variation or rs3815583 as a predictor of fatal outcomes in ACEI-treated patients with CHF.

Assessment of the risk of cardiovascular disease in patients with rosacea.

BACKGROUND: Recent studies have shown a higher prevalence of cardiovascular (CV) risk factors in patients with rosacea. However, it remains unknown whether rosacea represents an independent CV risk factor. OBJECTIVE: We evaluated the risk of myocardial infarction, stroke, CV death, major adverse CV events, and all-cause mortality, respectively. METHODS: Between January 1, 1997, and December 31, 2012, a total of 4948 patients with rosacea were identified and matched with 23,823 control subjects. We used Poisson regression to calculate incidence rate ratios. RESULTS: Adjusted incidence rate ratios were 0.75 (95% confidence intervals [CI] 0.57-1.00) for myocardial infarction, 1.08 (95% CI 0.86-1.35) for ischemic stroke, 1.01 (95% CI 0.61-1.67) for hemorrhagic stroke, 0.99 (95% CI 0.80-1.24) for CV death, 0.99 (95% CI 0.86-1.15) for major adverse CV events, and 0.95 (95% CI 0.85-1.06) for all-cause mortality. LIMITATIONS: We were unable to distinguish between the different subtypes and severities of rosacea. CONCLUSIONS: In this population-based study, rosacea was not associated with increased risk of adverse CV outcomes or death.

Family history predicts major adverse cardiovascular events (MACE) in young adults with psoriasis.

BACKGROUND: Patients with psoriasis may have increased risk of major adverse cardiovascular (CV) events (MACE), and a family history of CV disease (CVD) is an independent risk factor for MACE. OBJECTIVE: We investigated the risk of first-time MACE in patients with psoriasis with or without a family history of CVD. METHODS: Between January 1, 1997, and December 31, 2011, we identified 2,722,375 individuals, including 25,774 and 4504 patients with mild and severe psoriasis, through administrative registers. Incidence rate ratios were estimated by Poisson regression. RESULTS: Mean baseline age was 26.6 (SD 8.6) years. A family history of CVD was found among 16,080 (62.4%) and 3009 (66.8%) patients with mild and severe psoriasis, respectively. In patients with psoriasis and a family history of CVD, the adjusted incidence rate ratios (95% CI) of MACE were 1.28 (1.12-1.46) and 1.62 (1.14-2.30) for mild and severe disease, respectively. In patients with psoriasis but without a family history of CVD, there was no increased risk of MACE. LIMITATIONS: Results may not apply to late-onset psoriasis. CONCLUSIONS: A family history of CVD predicted the risk of first-time MACE in young adults with psoriasis. The findings call for increased focus on a family history of CVD in CV risk assessment of patients with psoriasis.

Effects of tofacitinib on cardiovascular risk factors and cardiovascular outcomes based on phase III and long-term extension data in patients with plaque psoriasis.

BACKGROUND: Psoriasis is a systemic inflammatory condition that is associated with a higher risk of cardiovascular (CV) disease. Tofacitinib is being investigated as a treatment for psoriasis. OBJECTIVE: We sought to evaluate the effects of tofacitinib on CV risk factors and major adverse CV events (MACEs) in patients with plaque psoriasis. METHODS: Changes in select CV risk factors and the incidence rate (IR) of MACEs were evaluated in patients who were treated with tofacitinib. RESULTS: Tofacitinib treatment was associated with small, dose-dependent increases in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, while the total/HDL cholesterol ratio was unchanged. There were no changes in blood pressure and glycated hemoglobin levels; C-reactive protein levels decreased. The IRs of a MACE were low and similar for both tofacitinib doses. Among 3623 subjects treated with tofacitinib, the total patient-years of exposure was 5204, with a median follow-up of 527 days, and the IR of MACEs was 0.37 (95% confidence interval, 0.22-0.57) patients with events per 100 patient-years. LIMITATIONS: There was relatively short follow-up time for patients who had MACEs. CONCLUSIONS: While treatment with tofacitinib is associated with a small increase in cholesterol levels, the total/HDL cholesterol ratio does not change, there are no unfavorable changes in several CV risk factors, and the incidence of MACEs is low.

Psoriasis and New-onset Depression: A Danish Nationwide Cohort Study.

Psoriasis is associated with an increased risk of depression, but results are inconsistent. This study examined the risk of new-onset depression in patients with psoriasis in a nationwide Danish cohort including some 5 million people in the period 2001-2011. A total of 35,001 patients with mild psoriasis and 7,510 with severe psoriasis were identified. Incidence rates per 1,000 person-years and incidence rate ratios (IRRs) were calculated. Incidence rates for depression were 20.0 (95% confidence interval 19.9-20.0), 23.9 (23.1-24.7) and 31.6 (29.5-33.8) for the reference population, mild, and severe psoriasis, respectively. Adjusted for age, sex, and inclusion year, IRRs were 1.08 (1.04-1.12) in mild and 1.36 (1.27-1.46) in severe psoriasis. After adjustment for comorbidity, the IRR was significant in only patients < 50 years with severe psoriasis (IRR 1.23 (1.03-1.46)). In conclusion, the risk of new-onset depression in psoriasis is mediated primarily by comorbidities, except in younger individuals with severe psoriasis, in whom psoriasis itself may be a risk factor.

Use of secondary prevention pharmacotherapy after first myocardial infarction in patients with diabetes mellitus.

BACKGROUND: Despite recommended pharmacotherapies the use of secondary prevention therapy after myocardial infarction (MI) remains suboptimal. Patients with diabetes mellitus (DM) have worse prognosis after MI compared to patients without DM and aggressive secondary prevention pharmacotherapy in this population is therefore warranted. We examined the changes in use of evidence-based secondary prevention pharmacotherapy in patients with and without DM discharged after first MI. METHODS: All patients aged 30 years or older admitted with first MI in Denmark during 1997-2006 were identified by individual-level linkage of nationwide registries of hospitalizations. Univariate and multivariate logistic regression models were used to identify patient characteristics associated with initiation of acetylsalicylic acid, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, ß-blockers, and clopidogrel within 90 days, and statins within 180 days of discharge, respectively. RESULTS: A total of 78,230 patients were included, the mean age was 68.3 years (SD 13.0), 63.5% were men and 9,797 (12.5%) had diabetes. Comparison of claimed prescriptions in the period 1997-2002 and 2003-2006 showed significant (p < 0.001) increases in claims for acetylsalicylic acid (38.9% vs. 69.7%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (38.7% vs. 50.4%), ß-blockers (69.2% vs. 77.9%), clopidogrel (16.7% vs. 66.3%), and statins (41.3% vs. 77.3%). During 2003-2006, patients with DM claimed significantly less acetylsalicylic acid (odds ratio [OR] 0.81 [95% confidence interval [CI] 0.74-0.88) and clopidogrel (OR 0.91 [95% CI 0.83-1.00]) than patients without DM. CONCLUSIONS: Despite sizeable increase in use of evidence-based secondary prevention pharmacotherapy after MI from 1997 to 2006, these drugs are not used in a substantial proportion of subjects and patients with DM received significantly less antiplatelet therapy than patients without DM. Increased focus on initiation of secondary prevention pharmacotherapy after MI is warranted, especially in patients with DM.

Effect of weight loss on the cardiovascular risk profile of obese patients with psoriasis.

Psoriasis is associated with obesity and other cardiovascular risk factors including endothelial dysfunction. We aimed to investigate the effects of weight loss on the cardiovascular risk profile of obese patients with psoriasis. A randomised controlled study was conducted in which we measured the microvascular endothelial function with peripheral arterial tonometry (PAT), selected plasma markers of endothelial function, and traditional cardiovascular risk factors in 60 obese patients with psoriasis. The participants were randomised to either low-energy diet (n = 30) providing 800-1,000 kcal/day for 8 weeks followed by 8 weeks of reduced food intake reaching 1,200 kcal/day or normal healthy foods (n = 30) for 16 weeks. The intervention group lost significantly more weight than controls, which resulted in significant reductions of diastolic blood pressure, resting heart rate, total cholesterol, VLDL cholesterol, triglyceride, plasma glucose, glycated haemoglobin, and tissue plasminogen activator inhibitor. Microvascular endothelial function assessed by PAT remained unchanged. We conclude that certain components of the cardiovascular risk profile of obese patients with psoriasis can be significantly improved by weight reduction.

The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

Long-term cardiovascular risk of nonsteroidal anti-inflammatory drug use according to time passed after first-time myocardial infarction: a nationwide cohort study.

BACKGROUND: The cardiovascular risk after the first myocardial infarction (MI) declines rapidly during the first year. We analyzed whether the cardiovascular risk associated with using nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with the time elapsed following first-time MI. METHODS AND RESULTS: We identified patients aged 30 years or older admitted with first-time MI in 1997 to 2009 and subsequent NSAID use by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. We calculated the incidence rates of death and a composite end point of coronary death or nonfatal recurrent MIs associated with NSAID use in 1-year time intervals up to 5 years after inclusion and analyzed risk by using multivariable adjusted time-dependent Cox proportional hazards models. Of the 99 187 patients included, 43 608 (44%) were prescribed NSAIDs after the index MI. There were 36 747 deaths and 28 693 coronary deaths or nonfatal recurrent MIs during the 5 years of follow-up. Relative to noncurrent treatment with NSAIDs, the use of any NSAID in the years following MI was persistently associated with an increased risk of death (hazard ratio 1.59 [95% confidence interval, 1.49-1.69]) after 1 year and hazard ratio 1.63 [95% confidence interval, 1.52-1.74] after 5 years) and coronary death or nonfatal recurrent MI (hazard ratio, 1.30 [95% confidence interval,l 1.22-1.39] and hazard ratio, 1.41 [95% confidence interval, 1.28-1.55]). CONCLUSIONS: The use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after first-time MI. We advise long-term caution in the use of NSAIDs for patients after MI.