Effectiveness and safety of alirocumab and evolocumab for hypercholesterolemia in a population with high cardiovascular risk.

BACKGROUND AND AIMS: The criteria for the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) more restrictive than those approved were established in Catalonia by the Health System (CatSalut) to improve their efficiency, with different LDL-C values from which to start treatment according to risk factors. The aim of the study is to analyse adherence to these criteria and results. METHODS: A retrospective study of patients treated with PCSK9i at Vall d'Hebron University Hospital between 2016 and 2021 was performed using data from the Registry of Patients and Treatments and medical records. The degree of agreement with the CatSalut criteria, LDL-C-responders (decrease ≥30%), cardiovascular events and discontinuations were analysed. RESULTS: A total of 193 patients treated with PCSK9i were followed for a median of 27 months (IQR 23). The median age was 61 (IQR 15); 62.7% were men. Seventy percent of the patients had non-familial hypercholesterolemia. Treatment was for secondary prevention of cardiovascular disease in 82.4% of cases. The median LDL-C decreased from 139 (IQR 52) to 59 (IQR 45) mg/dL. The percentage of LDL-C reduction was 61.0% (IQR 30). In 72.5% of patients, all CatSalut criteria for starting treatment were met. The rate of responders was 85.4%. During follow-up, 19 patients (9.8%) had a cardiovascular event, and 15 (7.7%) discontinued treatment, in two cases due to toxicity. CONCLUSION: PCSK9i were used according to CatSalut criteria in three out of four cases. In this high-risk population, incidence of cardiovascular events was similar to that in clinical trials.

Effect of statin therapy on SARS-CoV-2 infection-related mortality in hospitalized patients.

AIM: Assessing the effect of statin therapy (ST) at hospital admission for COVID-19 on in-hospital mortality. METHODS AND RESULTS: Retrospective observational study. Patients taking statins were 11 years older and had significantly more comorbidities than patients who were not taking statins. A genetic matching (GM) procedure was performed prior to analysis of the mortality risk. A Cox proportional hazards model was used for the cause-specific hazard (CSH) function, and a competing-risks Fine and Gray (FG) model was also used to study the direct effects of statins on risk. Data from reverse transcription-polymerase chain reaction-confirmed 2157 SARS-CoV-2-infected patients [1234 men, 923 women; age: 67 y/o (IQR 54-78)] admitted to the hospital were retrieved from the clinical records in anonymized manner. Three hundred and fifty-three deaths occurred. Five hundred and eighty-one patients were taking statins. Univariate test after GM showed a significantly lower mortality rate in patients on ST than the matched non-statin group (19.8% vs. 25.4%, χ2 with Yates continuity correction: P = 0.027). The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared with the GM non-statin group (17.4%; P = 0.045). The Cox model applied to the CSH function [HR = 0.58(CI: 0.39-0.89); P = 0.01] and the competing-risks FG model [HR = 0.60 (CI: 0.39-0.92); P = 0.02] suggest that statins are associated with reduced COVID-19-related mortality. CONCLUSIONS: A lower SARS-CoV-2 infection-related mortality was observed in patients treated with ST prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.

Long-term exposure to PM10 above WHO guidelines exacerbates COVID-19 severity and mortality.

BACKGROUND: Age, sex, race and comorbidities are insufficient to explain why some individuals remain asymptomatic after SARS-CoV-2 infection, while others die. In this sense, the increased risk caused by the long-term exposure to air pollution is being investigated to understand the high heterogeneity of the COVID-19 infection course. OBJECTIVES: We aimed to assess the underlying effect of long-term exposure to NO2 and PM10 on the severity and mortality of COVID-19. METHODS: A retrospective observational study was conducted with 2112 patients suffering COVID-19 infection. We built two sets of multivariate predictive models to assess the relationship between the long-term exposure to NO2 and PM10 and COVID-19 outcome. First, the probability of either death or severe COVID-19 outcome was predicted as a function of all the clinical variables together with the pollutants exposure by means of two regularized logistic regressions. Subsequently, two regularized linear regressions were constructed to predict the percentage of dead or severe patients. Finally, odds ratios and effects estimates were calculated. RESULTS: We found that the long-term exposure to PM10 is a more important variable than some already stated comorbidities (i.e.: COPD/Asthma, diabetes, obesity) in the prediction of COVID-19 severity and mortality. PM10 showed the highest effects estimates (1.65, 95% CI 1.32-2.06) on COVID-19 severity. For mortality, the highest effect estimates corresponded to age (3.59, 95% CI 2.94-4.40), followed by PM10 (2.37, 95% CI 1.71-3.32). Finally, an increase of 1 µg/m3 in PM10 concentration causes an increase of 3.06% (95% CI 1.11%-4.25%) of patients suffering COVID-19 as a severe disease and an increase of 2.68% (95% CI 0.53%-5.58%) of deaths. DISCUSSION: These results demonstrate that long-term PM10 burdens above WHO guidelines exacerbate COVID-19 health outcomes. Hence, WHO guidelines, the air quality standard established by the Directive 2008/50/EU, and that of the US-EPA should be updated accordingly to protect human health.

Low HDL and high triglycerides predict COVID-19 severity.

Lipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain the association of the plasma lipid profile with SARS-CoV-2 infection clinical evolution. Observational cross-sectional study including 1411 hospitalized patients with COVID-19 and an available standard lipid profile prior (n: 1305) or during hospitalization (n: 297). The usefulness of serum total, LDL, non-HDL and HDL cholesterol to predict the COVID-19 prognosis (severe vs mild) was analysed. Patients with severe COVID-19 evolution had lower HDL cholesterol and higher triglyceride levels before the infection. The lipid profile measured during hospitalization also showed that a severe outcome was associated with lower HDL cholesterol levels and higher triglycerides. HDL cholesterol and triglyceride concentrations were correlated with ferritin and D-dimer levels but not with CRP levels. The presence of atherogenic dyslipidaemia during the infection was strongly and independently associated with a worse COVID-19 infection prognosis. The low HDL cholesterol and high triglyceride concentrations measured before or during hospitalization are strong predictors of a severe course of the disease. The lipid profile should be considered as a sensitive marker of inflammation and should be measured in patients with COVID-19.

Changes in lipid profile between flare and remission of patients with systemic lupus erythematosus: a prospective study.

OBJECTIVE: To determine the lipid profile of patients with systemic lupus erythematosus (SLE) according to the disease activity, and to calculate the percentage of patients that diverged from optimal values. METHODS: Serum was collected from 52 patients with SLE at flare and at remission. SLE disease activity was measured by using the SLE Disease Activity Index (SLEDAI). Clinical and biological measures were evaluated in both situations. Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), and triglyceride (TG) levels were analyzed after overnight fasting. We also calculated the atherogenic ratios of TC/HDLC and LDLC/HDLC. RESULTS: SLE patients had significantly higher median TC/HDLC and LDLC/HDLC ratios at flare than during remission: 4.5 +/- 1.5 versus 3.9 +/- 1.0 (p = 0.007) and 2.7 +/- 1.1 versus 2.4 +/- 0.8 (p = 0.015), respectively. The differences persisted after adjustments based on kidney disease and treatment but not after adjusting by creatinine clearance < 60 ml/min/1.73 m(2) in remission. The variation between flare and remission of the percentage of SLE patients with high-risk levels of lipid profile to desirable values, and vice versa, was statistically significant for the LDLC/HDLC ratio (9 vs 1; p = 0.021). CONCLUSION: Our results reflect a higher risk of atherosclerosis phenomena in SLE patients during flare than during clinical remission. This might explain the propensity to develop coronary heart disease in patients with SLE.

Serum levels of soluble CD40 ligand at flare and at remission in patients with systemic lupus erythematosus.

OBJECTIVE: To perform a prospective evaluation of soluble CD40 ligand (sCD40L) levels according to the activity of systemic lupus erythematosus (SLE). METHODS: Two serum samples were taken from 53 patients with SLE: at flare and at remission. Clinical and biological measures (sCD40L levels were measured by a commercial ELISA) were evaluated in both situations. RESULTS: Patients with SLE had significantly lower median levels of sCD40L during flare than during remission [3365 (6157) vs 7125 (4122) pg/ml; p < 0.001]. The multivariate analysis to explain those patients with lower values of sCD40L during flare than during remission included 3 variables: 2 related to flare (prednisone dose received 192,000 x 10(6)/l) and one related to lower changes in SLE Disease Activity Index (SLEDAI) score. We regrouped patients with the 2 characteristics related to flare as Group 4, and the others were Group 123. All patients with low SLEDAI scores at flare had statistically significant lower sCD40L levels during flare than during remission. When flare SLEDAI scores were higher than the 50th percentile, patients of Group 123 showed the same behavior and even more diminished levels of sCD40L during flare than patients of Group 123 with low SLEDAI scores (p = 0.023); and patients of Group 4 showed no differences in the values of sCD40L between flare and remission (p = 0.241). CONCLUSION: sCD40L plays a biologically active role, with decreased levels at flare at low SLEDAI scores. At high SLEDAI scores there are mechanisms that involve platelets and that are inhibited by high doses of prednisone that lead to increased serum values of sCD40L at flare.