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Altered coagulation has been reported in people living with HIV (PLWH) with ongoing viral replication and may predispose to cardiovascular diseases. However, less is known about coagulation in PLWH with undetectable viral replication. In a cross-sectional observational study, we investigated whether HIV infection with undetectable viral replication is independently associated with activated partial thromboplastin time (APTT) and coagulation factor II–VII–X concentrations out of reference. Logistic regression analyses were used to assess the association of HIV infection with APTT and coagulation factor II–VII–X, after adjusting for age, sex, smoking status, alcohol consumption, BMI, diabetes and hsCRP. 936 PLWH with undetectable viral replication from the Copenhagen Co-morbidity in HIV infection study (COCOMO-study) and 2955 uninfected controls were included. Higher prevalence of short APTT was found in PLWH compared to controls (13.5% vs. 7.6%, P < 0.001). Furthermore, higher prevalence of low coagulation factor II–VII–X was found in PLWH than in controls (9.6% vs. 7.4%, P = 0.022). HIV was independently associated with short APTT (adjusted odds ratio (aOR) 2.3 (95% CI 1.7–2.9), P < 0.001) and low coagulation factor II–VII–X (aOR 1.4 (95% CI 1.0–1.9), P = 0.046). Few participants among PLWH and controls had both short APTT and low coagulation factor II–VII–X, 2.1% vs. 0.8%, respectively. We found evidence of both procoagulant (short APTT) and anticoagulant (low coagulation factor II–VII–X) alterations in PLWH with undetectable viral replication, and our findings suggest that two different coagulation phenotypes exist in participants with treated HIV infection. [ABSTRACT FROM AUTHOR]

New treatment opportunities are emerging in the field of lipid-lowering therapy through gene-silencing approaches. Both antisense oligonucleotide inhibition and small interfering RNA technology aim to degrade gene mRNA transcripts to reduce protein production and plasma lipoprotein levels. Elevated levels of LDL, remnant lipoproteins, and lipoprotein(a) all cause cardiovascular disease, whereas elevated levels of triglyceride-rich lipoproteins in some patients can cause acute pancreatitis. The levels of each of these lipoproteins can be reduced using gene-silencing therapies by targeting proteins that have an important role in lipoprotein production or removal (for example, the protein products of ANGPTL3, APOB, APOC3, LPA, and PCSK9). Using this technology, plasma levels of these lipoproteins can be reduced by 50-90% with 2-12 injections per year; such dramatic reductions are likely to reduce the incidence of cardiovascular disease or acute pancreatitis in at-risk patients. The reported adverse effects of these new therapies include injection-site reactions, flu-like symptoms, and low blood platelet counts. However, newer-generation drugs are more efficiently delivered to liver cells, requiring lower drug doses, which leads to fewer adverse effects. Although these findings are promising, robust evidence of cardiovascular disease reduction and long-term safety is needed before these gene-silencing technologies can have widespread implementation. Before the availability of such evidence, these drugs might have roles in patients with unmet medical needs through orphan indications. [ABSTRACT FROM AUTHOR]

Role and importance of vitamin D deficiency in long-term prognosis of chronic obstructive pulmonary disease (COPD) still remains undetermined. We tested the hypothesis that among individuals with COPD, those with low concentrations of 25-hydroxyvitamin D have a poorer prognosis compared to those with normal concentrations. We studied 35,153 individuals from the general population aged 20-100 years with 25-hydroxyvitamin D measurements and spirometry, the Copenhagen City Heart Study [median follow-up 21 years (range 13 days-36 years)] and the Copenhagen General Population Study [7.1 years (3 days-13 years)]. Spirometric COPD (n = 5178; 15% of all) was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.70 in individuals without asthma and clinical COPD (n = 2033; 6%) as FEV1/FVC < 0.70 and FEV1 < 80% of predicted in ever-smokers aged > 40 years without asthma and with cumulative tobacco consumption ≥ 10 pack-years. In spirometric COPD, median age at death in years was 70.2 (95% confidence interval [CI] 64.4-71.2) for individuals with 25-hydroxyvitamin D < 12.5 nmol/L and 80.3 (74.4-83.4) for those with ≥ 50 nmol/L. In clinical COPD, corresponding values were 69.0 (63.3-70.9) and 76.2 (73.8-78.0). In spirometric COPD, multivariable adjusted hazard ratios for individuals with 25-hydroxyvitamin D < 12.5 nmol/L versus those with ≥ 50 nmol/L were 1.35 (95% CI 1.09-1.67) for all-cause mortality, 1.63 (1.00-2.64) for respiratory mortality, 1.14 (0.76-1.70) for cardiovascular mortality, 1.37 (0.90-2.06) for cancer mortality, and 1.61 (1.04-2.49) for other mortality. In clinical COPD, corresponding values were 1.39 (1.07-1.82), 1.57 (0.91-2.72), 0.88 (0.51-1.53), 1.63 (0.99-2.67), and 2.00 (1.12-3.56). Low concentrations of 25-hydroxyvitamin D were associated with an increased risk of death in individuals with COPD. No clear pattern of association could be observed for cause of death; however, there may be an increased risk of respiratory, cancer, and other mortality. It is likely that low concentrations of 25-hydroxyvitamin D is a marker of poor health in COPD. [ABSTRACT FROM AUTHOR]