Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)

We aimed to explore the effect of PCSK9 inhibitor based on the background of statin on carotid intraplaque neovascularization (IPN) assessed by serial contrast-enhanced ultrasound (CEUS) analysis in Chinese patients with premature coronary artery disease (PCAD).

41 patients were included to receive treatments with biweekly evolocumab (n = 22) or placebo (n = 19) in addition to statin therapy for 52 weeks. All patients were newly diagnosed with PCAD and treatments were initiated at baseline of the observations. Baseline and 52-week CEUS were acquired to measure the max plaque height (MPH) and IPN. The primary outcome was the 52-week IPN changes, the secondary endpoints included the 52-week MPH changes and major adverse cardiovascular events.

The mean ± SD age of the participants was 46.76 ± 8.56 years, and 61% (25/41) of patients were on statins before the start of the study. There was no statistically significant difference in the history of statins treatment and the initiated lipid-lowering therapy of atorvastatin and rosuvastatin between groups (p > 0.05). At 52 weeks, the evolocumab group showed a lower LDL level (0.84 ± 0.45 mmol/L vs. 1.58 ± 0.51 mmol/L, p < 0.001) and a greater decrease in percent reduction of LDL-C level (−65% vs. −32%) and a higher percent of achieving lipid-lowering target (95% vs. 53%, p < 0.05) compared with the placebo group. At 52 weeks, IPN (evolocumab group: 0.50 ± 0.60 vs. 1.50 ± 0.80, p < 0.001; placebo group: 0.79 ± 0.54 vs. 1.26 ± 0.65, p < 0.05) and MPH (evolocumab group: 2.01 ± 0.44 mm vs. 2.57 ± 0.90 mm, p < 0.05, placebo group: 2.21 ± 0.58 mm vs. 2.92 ± 0.86 mm, p < 0.05) reduced significantly in both groups from baseline to 52-week follow-up. IPN and MPH were decreased by both treatments. Still, there was no significant difference in delta (52 weeks - baseline) MPH by an ANOVA analysis between the two groups [evolocumab group: −0.56 mm (2.01 mm–2.57 mm); placebo group: −0.71 mm (2.21 mm–2.92 mm), p > 0.05]. In the evolocumab group, the change in the mean reduction of IPN from baseline [-1.00 (0.50–1.50) vs. −0.47 (0.79–1.26), p < 0.05] and the incidence of patients with carotid IPN decrease were significantly greater reduction (90% vs. 58%, p < 0.05).

If compared to placebo, the PCSK9 inhibitor evolocumab combined with statins resulted in a greater decrease in LDL-C and plaque neovascularization in Chinese patients with PCAD.

High-density lipoprotein (HDL) has traditionally been acknowledged as "good cholesterol" owing to its significant association with a decreased risk of atherosclerosis. This association is primarily attributed to HDL's direct involvement in cholesterol efflux capacity, which plays a pivotal role in reverse cholesterol transport. A novel active compound from Nannochloropsis microalgae termed lyso-DGTS, a lipid that contains EPA fatty acids, was previously isolated and found to increase paraoxonase 1 activity and enhance HDL-mediated cholesterol efflux and HDL-induced endothelial nitric oxide release. Here, the effect of different lyso-DGTS derivatives and analogs on HDL-mediated cholesterol efflux from macrophages was examined, and the mechanism was explored. Structure–activity relationships were established to characterize the essential lipid moieties responsible for HDL-mediated cholesterol efflux from macrophages. Lyso-DGTS, 1-carboxy-N-N-N-trimethyl-3-oleamidopropan-1-aminium, and lyso-platelet-activating factor increased HDL-mediated cholesterol efflux from macrophages dose-dependently, mainly via the ABCA1-mediated cholesterol efflux pathway. The effect of lyso-DGTS derivatives and analogs on the surface polarity of HDL was examined using the Laurdan generalized polarization (GP) assay. A reverse Pearson linear regression was obtained between Laurdan GP values and HDL-mediated cholesterol efflux. Because the incorporation of bioactive lipids into the surface phospholipid layer of HDL leads to a decrease in Laurdan GP, these bioactive lipids may induce lower phospholipid ordering and greater free space on the HDL particle surface, thereby enhancing apolipoprotein A1 binding to the ABCA1 receptor and improving ABCA1 cholesterol-mediated efflux. Our findings suggest a beneficial effect of lyso-DGTS and its bioactive lipid derivatives on increasing HDL-mediated cholesterol efflux activity from macrophages, which may impact atherosclerosis attenuation.

Familial hypercholesterolemia (FH) is associated with lifelong elevated plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). Clinical recommendations and treatments have emerged to facilitate the management of FH patients. Their impact on the burden of FH is however not well documented.

To compare the burden of FH between patients hospitalized for a CHD event 25 years apart in the French-Canadian founder population.

Lipid profiles, cardiovascular risk factors, treatments and FH status of 2,029 patients consecutively hospitalized for an acute CHD event between 2017 and 2022 (2022 Cohort) were compared to those of 2,506 patients with angiographically-confirmed CHD who were admitted between 1995 and 1998 (1998 Cohort).

At the time of admission, 24.6 % of CHD patients had LDL-C levels >5.0 mmol/L in 1998 compared to 1.4 % in 2022, and FH was diagnosed in 9.6 % of patients in the 1998 cohort compared to 5.5 % in 2022 (p<0.001). FH patients hospitalized for a CHD event were older in 2022 than in 1998 (p <0.001). The prevalence of premature CHD requiring a hospitalization significantly decreased from 1998 to 2022 (64.3% vs. 44.1 %, p<0.001). At the moment of admission, 18.2 % of FH patients had LDL-C concentration <2.0 mmol/L in 2022 vs 0 % in 1998 (p <0.001).

Over 25 years, FH patients tend to be older and contribute to a lower proportion of hospitalizations for CHD in the French-Canadian founder population. Despite significant improvement in diagnosis and treatment, FH management remains however sub-optimal.

The secondary preventive medical remedies used in the U.S. general population, particularly those with numerous co-morbidities, are poorly understood. We aimed to assess health outcomes and the extent of their adherence to guideline-based secondary prevention medications among U.S. coronary heart disease (CHD) patients.

We analysed information from the U.S. National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 on people in the United States aged 18 to 85 who had a personal history of coronary heart disease (CHD). Logistic regression analyses were used to identify characteristics related to healthcare access that were linked with not taking any indicated drugs among CHD and other co-morbidity patients in the U.S.

We gathered 4256 CHD patients aged 18 and above. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), statins, and antiplatelet medications were taken by 50.94%, 48.26%, 53.41 %, and 19.78% of the population, respectively. Surprising, not received recommended drugs was reached up to 21.12%, and taking all four drugs was only 7.64%. In conclusion, the logistic regression analysis revealed that the chance of not taking prescribed drugs increased with age (18–39), race (Hispanic and Non-Hispanic Black), low income, lack of insurance, and the absence of co-morbidities (hypertension, heart failure, and diabetes mellitus).

The gap between the proposed secondary preventative measures and their actual execution remains sizable. In order to achieve ‘Healthy Aging’, a systematic approach for prevention of CHD is urgently needed.

The presented paper describes a new isolation method of recovery and analysis of selected drugs developed for preclinical research.

The method uses the RP-HPLC technique (in a single chromatographic separation) and serves the recovery and analysis of selected drugs from neoplastic cells. It enables the determination of cytostatics statins, fibrates, and pioglitazone. Chromatographic separations of the tested compounds were carried out on a Gemini-NX 5 µ C18 (4.6 × 150 mm i.d.) column, in a gradient system with a mobile phase consisting of ACN (0.1% TFA) and water (0.1% TFA) at ambient temperature. The separations were carried out at a flow of 1 ml/min and UV detection of 220 nm. The inter-day and intra-day precision and accuracy of the method were determined. Extending the extraction time at reduced temperature resulted in a significant increase in the recovery of the pharmaceuticals in comparison with traditional extraction methods.

The presence of the tested pharmaceuticals at defined retention times was confirmed by mass spectrometry. A recovery procedure for the tested compounds from biological material (medium, cell pellets) was developed at a level ranging between 93 and 99%. The utility of the new HPLC method has been confirmed in drug absorption studies as screening tests for the analysis of the new therapeutic compositions on melanoma cell lines.

La incidencia de las enfermedades arterioscleróticas ha aumentado en los países desarrollados. La dislipemia es un factor de riesgo cardiovascular mayor y el descenso del LDLc es el objetivo terapéutico. Hay que individualizar los objetivos en cada paciente y las estatinas han demostrado ser un tratamiento coste-efectivo tanto en prevención primaria como en secundaria. La aparición de los inhibidores de PSCK9, más potentes y por tanto consiguiendo un mayor descenso de las cifras de LDLc, son un avance en el tratamiento de la enfermedad cardiovascular. La publicación en 2019 de las Guías de Dislipemias (Sociedad Europea de Cardiología /Sociedad Europea de Arteriosclerosis) con el nivel de evidencia y fuerza de recomendación, pueden ayudar en la toma de decisiones y beneficios para nuestros pacientes en la práctica clínica diaria.

The incidence of atherosclerotic cardiovsacular disease (ASCVC) has increased in the developed countries. Dyslipidemia is a primary major risk factor for ASCVD and LDL lowering is one of the main objectives. Although treatment goals for dyslipidemias should be personalized in every patient, statins are cost-effective in primary and secondary prevention of ASCVD. New treatments with higher power and greater decreases in LDL, PSCK9 inhibitors, have made a new breakthrough in ASCVD treatment. The 2019 Guidelines for de Management of Dyslipidaemias: Lipid Modification to reduce Cardiovascular Risk (European Society of Cardiology/European Atherosclerosis Society) with the level of evidence and the strength of the recommendations can facilitate the best decisions and benefits to our patients in clinical practice.