Atherosclerosis

2023

DOI: 10.1016/j.atherosclerosis.2023.06.971

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Evidence of an anti-inflammatory effect of PCSK9 inhibitors within the human atherosclerotic plaque

Raffaele Marfella

¹

,

Francesco Prattichizzo

²

,

Celestino Sardu

³

et al.

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Introduction3

Discussion1

The Faces Of Atherosclerosis1

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2023

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Cited by 21 publications

(10 citation statements)

References 47 publications

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“…EAT thickness is a marker for visceral adiposity and related metabolic alterations, and PCSK9 might be one of the factors responsible for the development of atherogenic dyslipidemia. In this context, further studies, including those with newly drugs such as monoclonal antibody against PCSK9 and synthetic small RNA that interferes PCSK9 transcription 46 , 47 , could contribute to acquire a more detailed understanding of the link between PCSK9 and EAT volume and to determine its contribution to dyslipidemia and increased CVD risk associated with T1D.…”

Section: Discussionmentioning

confidence: 99%

PCSK9 plasma concentration is associated with epicardial adipose tissue volume and metabolic control in patients with type 1 diabetes

Sardà,

Colom,

Benitez

et al. 2024

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Patients with type 1 diabetes (T1D) have a greater risk of cardiovascular disease. Proconvertase subtilisin-kexin 9 (PCSK9) is involved in the atherosclerosis process. This study aimed to determine the relationship between PCSK9 levels and epicardial adipose tissue (EAT) volume and cardiometabolic variables in patients with T1D. This was an observational cross-sectional study including 73 patients with T1D. Clinical, biochemical and imaging data were collected. We divided the patients into two groups according to their glycemic control and the EAT index (iEAT) percentile. We performed a correlation analysis between the collected variables and PCSK9 levels; subsequently, we performed a multiple regression analysis with the significant parameters. The mean age was 47.6 ± 8.5 years, 58.9% were men, and the BMI was 26.9 ± 4.6 kg/m2. A total of 31.5%, 49.3% and 34.2% of patients had hypertension, dyslipidemia and smoking habit, respectively. The PCSK9 concentration was 0.37 ± 0.12 mg/L, which was greater in patients with worse glycemic control (HbA1c > 7.5%), dyslipidemia and high EAT volume (iEAT > 75th percentile). The PCSK9 concentration was positively correlated with age (r = 0.259; p = 0.027), HbA1c (r = 0.300; p = 0.011), insulin dose (r = 0.275; p = 0.020), VLDL-C level (r = 0.331; p = 0.004), TG level (r = 0.328; p = 0.005), and iEAT (r = 0.438; p < 0.001). Multiple regression analysis revealed that 25% of the PCSK9 variability was explained by iEAT and HbA1c (p < 0.05). The PCSK9 concentration is associated with metabolic syndrome parameters, poor glycemic control and increased EAT volume in patients with T1D.

“…EAT thickness is a marker for visceral adiposity and related metabolic alterations, and PCSK9 might be one of the factors responsible for the development of atherogenic dyslipidemia. In this context, further studies, including those with newly drugs such as monoclonal antibody against PCSK9 and synthetic small RNA that interferes PCSK9 transcription 46 , 47 , could contribute to acquire a more detailed understanding of the link between PCSK9 and EAT volume and to determine its contribution to dyslipidemia and increased CVD risk associated with T1D.…”

Section: Discussionmentioning

confidence: 99%

PCSK9 plasma concentration is associated with epicardial adipose tissue volume and metabolic control in patients with type 1 diabetes

Sardà,

Colom,

Benitez

et al. 2024

View full text Add to dashboard Cite

Patients with type 1 diabetes (T1D) have a greater risk of cardiovascular disease. Proconvertase subtilisin-kexin 9 (PCSK9) is involved in the atherosclerosis process. This study aimed to determine the relationship between PCSK9 levels and epicardial adipose tissue (EAT) volume and cardiometabolic variables in patients with T1D. This was an observational cross-sectional study including 73 patients with T1D. Clinical, biochemical and imaging data were collected. We divided the patients into two groups according to their glycemic control and the EAT index (iEAT) percentile. We performed a correlation analysis between the collected variables and PCSK9 levels; subsequently, we performed a multiple regression analysis with the significant parameters. The mean age was 47.6 ± 8.5 years, 58.9% were men, and the BMI was 26.9 ± 4.6 kg/m2. A total of 31.5%, 49.3% and 34.2% of patients had hypertension, dyslipidemia and smoking habit, respectively. The PCSK9 concentration was 0.37 ± 0.12 mg/L, which was greater in patients with worse glycemic control (HbA1c > 7.5%), dyslipidemia and high EAT volume (iEAT > 75th percentile). The PCSK9 concentration was positively correlated with age (r = 0.259; p = 0.027), HbA1c (r = 0.300; p = 0.011), insulin dose (r = 0.275; p = 0.020), VLDL-C level (r = 0.331; p = 0.004), TG level (r = 0.328; p = 0.005), and iEAT (r = 0.438; p < 0.001). Multiple regression analysis revealed that 25% of the PCSK9 variability was explained by iEAT and HbA1c (p < 0.05). The PCSK9 concentration is associated with metabolic syndrome parameters, poor glycemic control and increased EAT volume in patients with T1D.

“…A greater emphasis should be placed on ‘hardening of the vessels’ affected by atherosclerosis and improving arterial compliance to improve the prognosis, reduce symptoms, and strengthen the blood supply to target organs (brain, kidney, lower limb muscles, etc.) [ 66 , 67 , 68 , 69 ]. Surgical and endovascular interventions should be reserved for emergencies and life-threatening situations.…”

Section: The Faces Of Atherosclerosismentioning

confidence: 99%

A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients—A Review: Part I—Epidemiology, Risk Factors, and Atherosclerosis-Related Diversities in Elderly Patients

Piechocki,

Przewłocki,

Pieniążek

et al. 2024

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Atherosclerosis is a generalized and progressive disease. Ageing is a key risk factor for atherosclerosis progression that is associated with the increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in adults ≥ 75 years of age. Atherosclerotic occlusive disease affects everyday activity and quality of life, and it is associated with reduced life expectancy. Although there is evidence on coronary artery disease management in the elderly, there is insufficient data on the management in older patients presented with atherosclerotic lesions outside the coronary territory. Despite this, trials and observational studies systematically exclude older patients, particularly those with severe comorbidities, physical or cognitive dysfunctions, frailty, or residence in a nursing home. This results in serious critical gaps in knowledge and a lack of guidance on the appropriate medical treatment and referral for endovascular or surgical interventions. Therefore, we attempted to gather data on the prevalence, risk factors, and management strategies in patients with extra-coronary atherosclerotic lesions.

“…MI is primarily caused by coronary artery embolism, whereas AF mainly results from structural changes induced by ischemia and over-inflammation [ 2 , 4 , 5 ]. The mechanisms of atherosclerosis, as well as over-oxidation and inflammation, are mainly responsible for atherosclerotic plaque instability, rupture, and acute coronary events [ 6 , 7 ]. Furthermore, patients with recurrent AF exhibited elevated inflammation marker levels, while the persistence of AF was found to exert a detrimental influence on atrial over-inflammation, oxidation, and fibrosis through epigenetic regulation [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Opposite causal effects of birthweight on myocardial infarction and atrial fibrillation and the distinct mediating pathways: a Mendelian randomization study

Kong,

Wang,

Ye

et al. 2023

Cardiovasc Diabetol

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Background Previous observational studies have documented an inverse association of birthweight with myocardial infarction (MI) but a positive association with atrial fibrillation (AF). However, the causality of these associations and the underlying mediating pathways remain unclear. We aimed to investigate the causal effects of birthweight, incorporating both fetal and maternal genetic effects, on MI and AF, and identify potential mediators in their respective pathways. Methods We performed Mendelian randomization (MR) analyses using genome-wide association study summary statistics for birthweight (N = 297,356 for own birthweight and 210,248 for offspring birthweight), MI (Ncase=61,000, Ncontrol=577,000), AF (Ncase=60,620, Ncontrol=970,216), and 52 candidate mediators (N = 13,848-1,295,946). Two-step MR was employed to identify and assess the mediation proportion of potential mediators in the associations of birthweight with MI and AF, respectively. As a complement, we replicated analyses for fetal-specific birthweight and maternal-specific birthweight. Results Genetically determined each 1-SD lower birthweight was associated with a 40% (95% CI: 1.22–1.60) higher risk of MI, whereas each 1-SD higher birthweight was causally associated with a 29% (95% CI: 1.16–1.44) higher risk of AF. Cardiometabolic factors, including lipids and lipoproteins, glucose and insulin, blood pressure, and fatty acids, each mediated 4.09-23.71% of the total effect of birthweight on MI, followed by body composition and strength traits (i.e., appendicular lean mass, height, and grip strength) and socioeconomic indicators (i.e., education and household income), with the mediation proportion for each factor ranging from 8.08 to 16.80%. By contrast, appendicular lean mass, height, waist circumference, childhood obesity, and body mass index each mediated 15.03-45.12% of the total effect of birthweight on AF. Both fetal-specific birthweight and maternal-specific birthweight were inversely associated with MI, while only fetal-specific birthweight was positively associated with AF. Psychological well-being and lifestyle factors conferred no mediating effect in either association. Conclusions Cardiometabolic factors mainly mediated the association between lower birthweight and MI, while body composition and strength traits mediated the association between higher birthweight and AF. These findings provide novel evidence for the distinct pathogenesis of MI and AF and advocate adopting a life-course approach to improving fetal development and subsequent causal mediators to mitigate the prevalence and burden of cardiovascular diseases.

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