Clínica e Investigación en Arteriosclerosis (English Edition)最新文献

Diabetes, especially type 2 (DM2), is considered a risk situation for atherosclerotic cardiovascular disease (ASCVD). Subjects with DM2 have a mortality rate due to ASCVD three times higher than that found in the general population, attributed to hyperglycemia and the frequent association of other cardiovascular risk factors, such as atherogenic dyslipidemia.

Numerous scientific societies have established a risk classification for ASCVD in diabetes based on 3 degrees (moderate, high and very high). The objectives of dyslipidemia control are clearly defined and accepted, and vary depending on the previously established cardiovascular risk.

In moderate or intermediate risk, the guidelines propose a less aggressive intervention, maintaining LDL-C levels <100 mg/dL and NO-HDL-C levels <130 mg/dL, and waiting 10 years until reaching the high-risk category to initiate more aggressive treatment. However, during the decade of follow-up recommended in the guidelines, cholesterol deposition in the arterial wall increases, facilitating the development of an unstable and inflammatory atheromatous plaque, and the development of ASCVD. Alternatively, diabetes could be considered from the outset to be a high-risk situation and the goal should be LDL-C <70 mg/dL. Furthermore, maintaining LDL-C levels <70 mg/dL contributes to reducing and stabilizing atheromatous plaque, avoiding or reducing mortality episodes due to ASCVD during those years of diabetes evolution.

Should we maintain the proposed objectives in subjects with diabetes and moderate risk for a decade until reaching the high cardiovascular risk phase or, on the contrary, should we adopt a more aggressive stance from the beginning seeking to reduce cardiovascular risk in the majority of patients with diabetes? Is it better to wait or prevent with effective therapeutic measures from the first moment?

Objective

Multiple systematic reviews (SR) have been performed on the effects of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), often providing conflicting findings. This overview and network meta-analysis (NMA) aimed to summarize SR findings on the efficacy and safety of PCSK9i and provide an updated NMA.

Materials and methods

MEDLINE (Pubmed), Scopus, Cochrane, Epistemonikos and Google Scholar were searched from inception to September 21, 2023 for SRs of randomized controlled trials (RCTs) and from January 1, 2020 to September 21, 2023 for additional RCTs. Double-independent study selection, data extraction and quality assessment were performed. Qualitative analysis was performed for SRs and a frequentist random-effects model NMA was performed for RCTs.

Results

Totally, 86 SRs and 76 RCTs were included. Alirocumab (77/86 [90%]) and evolocumab (73/86 [85%]) were mostly analyzed. Associations from SRs (35/42 [83%]) and the updated NMA indicated PCSK9i benefit on major adverse cardiovascular events (MACEs). Reductions were also noted for cerebrovascular events (47/66 [71%]), coronary revascularization (29/33 [88%]) and myocardial infarction (41/63 [65%]). Alirocumab was associated with reductions on all-cause mortality (RR = 0.82, 95%CI [0.72,0.94]). Data on any CV event reduction were conflicting (7/16 [44%]). Inclisiran appeared effective only on MACEs (RR = 0.76, 95%CI [0.61,0.94]). No reductions in heart failure were observed (0/16). No increases were identified between PCSK9i and any (0/35) or serious adverse events (0/52). However, PCSK9i were associated with injection-site reactions (20/28 [71%]).

Conclusion

PCSK9i appeared to be effective in CV outcomes and their clinical application was generally safe.

Background

Combined oral contraceptives (COCs), use in individuals are associated with increased risk of thrombotic events. This highlights the significance of assessing the impact of COC on promoting coagulation and endothelial activation in high-fat diet (HFD)-fed Sprague Dawley rats.

Methods

Twenty (20) five-weeks-old female Sprague Dawley rats weighing between 150 and 200 g were subjected to both LFD and HFD-feeding for 8-weeks to determine its influence on basic metabolic status, hemostatic profile, hemodynamic parameters (blood pressure and heart rate), as well as selected biomarkers of coagulation (tissue factor and D-dimer) and endothelial activation (Von Willebrand factor and nitric oxide). Thereafter HFD-fed animals were treated with receive high dose combined oral contraceptive (HCOC) and low dose combine oral contraceptive (LCOC) for 6 weeks.

Results

Our results showed that beyond weight gain, HFD-feeding was associated with hyperglycemia, increased mean arterial pressure, and reduced nitric oxide levels when compared with LFD group (p < 0.05). Interestingly, treatment with high dose of COC for 6-weeks did not significantly alter atherothrombotic markers (p > 0.05). However, this study is not without limitation as regulation of these markers remains to be confirmed within the cardiac tissues or endothelial cells of these animals.

Conclusion

HFD-feeding orchestrate the concomitant release of pro-coagulants and endothelial activation markers in rats leading to haemostatic imbalance and endothelial dysfunction. Short-term treatment with COC shows no detrimental effects in these HFD-fed rats. Although in terms of clinical relevance, our findings depict the notion that the risk of CVD in association with COC may depend on the dosage and duration of use among other factors especially in certain conditions. However, additional studies are required to confirm these findings, especially long-term effects of this treatment within the cardiac tissues or endothelial cells of these animals in certain conditions relating to postmenopausal state.

Objectives

Sleep disturbances, including disrupted sleep and short sleep duration, are highly prevalent and are prospectively associated with an increased risk for various chronic diseases, including cardiometabolic, neurodegenerative, and autoimmune diseases.

Material and methods

This is a narrative review of the literature based on numerous articles published in peer-reviewed journals since the beginning of this century.

Results

The relationship between sleep disorders and metabolic dysregulation has been clearly established, mainly in the setting of modern epidemic of cardiometabolic disease, a cluster of conditions include obesity, insulin resistance, arterial hypertension, and dyslipidaemia, all of them considered as main risk factor for atherosclerotic cardiovascular disease (ACVD) and its clinical expression such as ischemic ictus, myocardial infarction and type 2 diabetes. Clinically viable tools to measure sleep duration and quality are needed for routine screening and intervention.

Conclusions

In view of what has been exposed in this review, it is evident that the timing, amount, and quality of sleep are critical to reduce the burden of risk factors for several chronic disease, including ACVD and type 2 diabetes, and most relevant in young people. Future research studies should elucidate the effectiveness of multimodal interventions to counteract the risk of short sleep for optimal patient outcomes across the healthcare continuum, especially in young people.

Introduction

Current guidelines recommend cardiovascular risk assessment as a preventive measure for cardiovascular diseases, whose fundamental etiology is arteriosclerosis. One of the tools used to estimate risk in clinical practice are atherogenic indices (AI), ratios between lipid fractions with well-established reference ranges. Despite its widespread use, there is still limited information on its clinical utility. In recent years, some research has reinforced the role of inflammation in the etiology and chronicity of the atherosclerotic process. The inclusion of inflammatory parameters in the AI ​​calculation could improve its diagnostic performance in the detection of arteriosclerosis. We sought to evaluate a new AI as a ratio between C-reactive protein (CRP) values ​​and high-density lipoprotein cholesterol (HDL) values.

Methods

A total of 282 asymptomatic patients with no history of cardiovascular disease were included in the study. Laboratory tests with lipid profile and CRP, and carotid ultrasound to assess the presence of atheromatosis were performed in all of them. The new AI is established as the ratio between non-ultrasensitive CRP value in mg/dL (multiplied by 100) and HDL value in mg/dL. It was compared with the Castelli I and II indices, and the plasma atherogenic index. The optimal cut-off point of the new AI was value = 1 as determined by ROC curve, with an area under the curve of 0.678 (95% CI 0.60−0.75, P < .001).

Results

Mean age of patients was 60.4 ± 14.5 years. 118 patients (41.8% of total) had carotid arteriosclerosis. When evaluating the diagnostic performance of different AIs, we found that CRP·100/HDL ratio showed the highest values ​​of sensitivity and positive predictive value (0.73 and 0.68, respectively) compared to the Castelli I and II indices, and the plasma atherogenic index. It was also the only predictor of carotid atheromatosis both when considering its values ​​quantitatively [with OR 1.4 (95% CI 1.1−1.7, P = .005)], and qualitatively [with OR 2.9 (95% CI 1.5–5.5, P < .001) in patients with a CRP·100/HDL ratio >1].

Conclusions

The new PCR·100/HDL index showed the best diagnostic performance in the detection of carotid atheromatosis compared to other classic AIs in this Spanish population of asymptomatic patients.

“The lower, the better” is the recommended approach in the management of high LDL cholesterol. Unfortunately, this does not always achieve as in the case of a 69-year-old woman referred to our Institute for her lipid profile (LDL cholesterol 412 mg/dl), bilateral xanthelasma and cutaneous xanthomas. With a maximized and personalized lipid-lowering therapies (rosuvastatin, ezetimibe, PCSK9i and lipoprotein apheresis), after only six months, the patient showed an impressive regression in her cutaneous xanthomas.

Background

Cardiovascular disease (CVD) represents the primary cause of death and disability globally, with elevated cholesterol as one of the leading risk factors for CVD. We describe the clinical characteristics, treatment patterns, and effectiveness of evolocumab in treating hyperlipidemia.

Methods

Observational study conducted through a chart review of patients with hyperlipidemia receiving evolocumab as part of clinical management in Colombia.

Results

This study included 115 patients treated with evolocumab. A total of 101 patients (87.8%) had a history of CVD, 13 (11.3%) familial hypercholesterolemia (FH), and 23 (20%) type 2 diabetes. Thirty-nine patients reported intolerance to any statin (33.9%). The median value of LDL-C before initiation of evolocumab was 147 mg/dL (IQR: 122.5–183.7 mg/dL). Within the first 3 months of treatment, LDL-C value dropped to a median value of 53 mg/dL (IQR: 34.0–95.5 mg/dL), showing a reduction of 63.9%. The median LDL-C values remained below 45 mg/dL until the end of follow-up. Among the patients with available data, up to 61% achieved an LDL-C level below 55 mg/dL at the 10–12-month follow-up. A total of 72% of patients were persistent with treatment. Safety results showed a low frequency of hospitalizations (≤2%) and treatment-emergent adverse drug reactions (5.2%). No serious adverse events were reported.

Conclusions

Evolocumab was associated with reductions in LDL-C levels, with a relative decrease of 63.9% within the first 3 months of treatment. Low rates of interruptions due to adverse events and adequate medication persistence was reported.

Objective

To examine the frequency of severe hypercholesterolemia (HS) and its clinical profile, and the phenotype of familial hypercholesterolemia (FH), in the primary-care setting in a large health area of ​​the Community of Madrid (CAM).

Material and methods

Multicenter study of subjects with a health card assigned to 69 health centers (Northwest/CAM area). HS was defined as cholesterol ≥ 300 mg/dL or LDL-cholesterol ≥ 220 mg/dL in any analysis performed (1-1-2018 to 12-30-2021); and FH phenotype as c-LDL ≥ 240 mg/dL (≥160 mg/dL if lipid-lowering treatment) with triglycerides < 200 mg/dL and TSH < 5 uIU/ml.

Results

156,082 adults ≥ 18 years with an available lipid profile were analyzed. 6187 subjects had HS (3.96% of the laboratory tests studied, 95%CI 3.87%–4.06%). The mean evolution time of the diagnosis of hyperlipidemia in the computerized clinical record was 10.8 years; 36.5% had hypertension; 9.5% diabetes and 62.9% overweight/obesity. 83.7% were taking lipid-lowering drugs (65,7% low/moderate and 28.6% high/very high intensity). 6.1% had cardiovascular disease (94.2% treated with lipid-lowering agents), with LDL-cholesterol <55, <70 and <100 mg/dl of 1.8%, 5.8% and 20.2%, respectively. (vs 1%, 2.3% and 11.2% if no cardiovascular disease). 1600 subjects had FH phenotype (1.03%, 0.98%–1.08%).

Conclusions

Four out of 100 patients analyzed in primary care have HS, with high treatment level, but insufficient intensity, and poor achievement of treatment goals. One in 100 have the FH phenotype. The identification of both dyslipidemias by computerized records would allow their more precise and early detection and establish cardiovascular preventive strategies.