Global epidemiology of dyslipidaemias Pirillo, Angela; Casula, Manuela; Olmastroni, Elena ...
Nature reviews cardiology,
10/2021, Letnik:
18, Številka:
10
Journal Article
Recenzirano
Dyslipidaemias are alterations to the plasma lipid profile that are often associated with clinical conditions. Dyslipidaemias, particularly elevated plasma LDL-cholesterol levels, are major risk ...factors for cardiovascular disease, but some forms, such as hypertriglyceridaemia, are associated with severe diseases in other organ systems, including non-alcoholic fatty liver disease and acute pancreatitis. Dyslipidaemias can be genetically determined (primary or familial dyslipidaemias) or secondary to other conditions (such as diabetes mellitus, obesity or an unhealthy lifestyle), the latter being more common. Hypercholesterolaemia is the most common form of dyslipidaemia and is associated with an increased risk of cardiovascular disease, with elevated plasma LDL-cholesterol levels being the 15th leading risk factor for death in 1990, rising to 11th in 2007 and 8th in 2019. The global burden of dyslipidaemias has increased over the past 30 years. Furthermore, the combination of high triglyceride levels and low HDL-cholesterol levels (together with the presence of small, dense LDL particles), referred to as atherogenic dyslipidaemia, is highly prevalent in patients with diabetes or metabolic syndrome and increases their risk of cardiovascular disease. Given the increasing prevalence of diabetes worldwide, treating lipid abnormalities in these patients might reduce their risk of cardiovascular disease.
The subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins is a critical step in the initiation of pro-atherosclerotic processes. Recent genetic and clinical evidence strongly ...supports the concept that the lipid content of the particles is secondary to the number of circulating atherogenic particles that are trapped within the arterial lumen. Since each low-density lipoproteins (LDL) particle contains one apoB molecule, as do intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, apoB level represents the total number of atherogenic lipoproteins, which is independent of particle density, and not affected by the heterogeneity of particle cholesterol content (clinically evaluated by LDL-cholesterol level). From this perspective, apoB is proposed as a better proxy to LDL-cholesterol for assessing atherosclerotic cardiovascular disease risk, especially in specific subgroups of patients, including subjects with diabetes mellitus, with multiple cardiometabolic risk factors (obesity, metabolic syndrome, insulin resistance, and hypertension) and with high triglyceride levels and very low LDL-cholesterol levels. Therefore, given the causal role of LDL-cholesterol in atherosclerotic cardiovascular disease (ASCVD) development, routine measurement of both LDL-cholesterol and apoB is of utmost importance to properly estimate global cardiovascular risk and to determine the 'residual' risk of ASCVD in patients receiving therapy, as well as to monitor therapeutic effectiveness.
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Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity worldwide. Low-density lipoprotein cholesterol (LDL-C) is one of the most important causal factors for ...ASCVD. Based on the evidence of the clinical benefits of lowering LDL-C, the current 2019 European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines provide guidance for optimal management of people with dyslipidaemia. These guidelines include new and revised concepts, with a general tightening of LDL-C goals to be achieved, especially for patients at high and very high cardiovascular risk, based on the results of clinical trials of the recently approved drugs for the treatment of hypercholesterolaemia. However, some issues are still open for discussion. Among others, the concept of lifetime exposure to elevated LDL-C levels will probably drive the pharmacological approach and future guidelines. In addition, other factors such as non-HDL-C, apolipoprotein B, and lipoprotein(a) are becoming increasingly important in determining cardiovascular risk. Finally, there is the question of whether combination therapy should be used as the first step to maximise the effectiveness of the pharmacological approach, avoiding the stepwise approach, which is likely to have a detrimental effect on adherence. Given the ever-changing landscape and the availability of new drugs targeting other important lipids, future guidelines will need to consider all these issues.
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The use of nutraceutical products and functional foods in the cardiovascular and metabolic field is rising in several countries. Preparation and implementation of guidelines are pivotal for ...translating research-derived knowledge and evidence-based medicine to the clinical practice. Based on these considerations, the aim of this paper is to explore if and how nutraceutical products are discussed by the most recent international guidelines related to cardio-metabolic diseases (dyslipidaemia, obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) prevention). Some, but not all, guidelines for dyslipidaemia mention nutraceutical products as potential useful options for the treatment of mild dyslipidaemia, but also indicate the low level of evidence associated to their effects on hard endpoints (myocardial infarction, stroke, CVD-related death). In the most recent guidelines on obesity, it is mentioned that no safe and effective dietary supplement nor nutraceutical product is available for the management of weight loss in this condition, and more high-quality studies are necessary in this field. The examined guidelines for T2DM do not mention any specific nutraceutical approach to this disease, nor to milder forms, such as insulin resistance and pre-diabetes.
The focus on nutraceutical products in the main international guidelines for cardio-metabolic disease management remains limited. Since robust scientific evidence is the background of useful and effective guidelines, the implementation of high-quality clinical research is strongly needed in the field of nutraceutical products for cardio-metabolic diseases.
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•Recently, the REDUCE-IT study has reopened the debate about the CV benefit of omega-3 fatty acids.•n-3 PUFA supplementation significantly reduced cardiac mortality, major adverse ...cardiovascular events, and myocardial infarction.•These effects are seen only with dose >1 g/day and in patients at higher CV risk.•n-3 PUFA significantly reduced cardiac mortality, major adverse cardiovascular events, and myocardial infarction.
The recent publication of the REDUCE-IT study has reopened the debate about the efficacy of omega-3 fatty acids in reducing the risk of cardiovascular (CV) events. This meta-analysis aims at investigating the effect of omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA) administration on CV outcomes in published randomized clinical trials (RCTs), with a focus on the role of dose, type of n-3 PUFA, and different CV risk at baseline.
This meta-analysis was conducted according to the PRISMA reporting guidelines. PubMed, Cochrane and EMBASE were searched since inception to March 2020. Inclusion criteria were: (1) RCTs; (2) including subjects with previous CV events; (3) administration of n-3 PUFA ≥ 1 g/day dosage for ≥1 year; (4) effects on all-cause mortality, cardiac death, major adverse cardiovascular events (MACE), fatal/nonfatal myocardial infarction (MI), or fatal/nonfatal stroke reported. Odds ratios (ORs) with 95 % confident intervals (95 %CI) were estimated.
16 RCTs were included in the meta-analysis accounting for 81,073 participants. Supplementation of n-3 PUFA was associated with a significant risk reduction of cardiac mortality (OR 0.91 95 % CI, 0.85−0.98), MACE (OR 0.90 95 % CI, 0.82−0.99), and MI (OR 0.83 95 % CI, 0.71−0.98). In subgroup analyses, the risk reduction of cardiac mortality and MI was confirmed only in RCTs that enrolled patients in secondary prevention (-21 % and -31 %, respectively). Moreover, only the administration of more than 1 g per day of n-3 PUFA was effective in reducing the risk of cardiac death (-35 %), MACE (-24 %), and MI (-33 %). Finally, EPA + DHA supplementation was only associated with a significant risk reduction of cardiac death compared with EPA administered alone (-8 %). Conversely, the efficacy of EPA administered alone seemed to be greater in terms of risk reduction of MACE (-25 %) or MI (-30 %) than the combined EPA + DHA supplementation.
The pharmacological approach with n-3 PUFA significantly improves cardiovascular outcomes, with higher benefit achieved by patients in secondary CV prevention, using more than 1 g/day, and taking EPA administered alone.
For a long time, high-density lipoprotein cholesterol (HDL-C) has been regarded as a cardiovascular disease (CVD) protective factor. Recently, several epidemiological studies, while confirming low ...plasma levels of HDL-C as an established predictive biomarker for atherosclerotic CVD, indicated that not only people at the lowest levels but also those with high HDL-C levels are at increased risk of cardiovascular (CV) mortality. This “U-shaped” association has further fueled the discussion on the pathophysiological role of HDL in CVD. In fact, genetic studies, Mendelian randomization approaches, and clinical trials have challenged the notion of HDL-C levels being causally linked to CVD protection, independent of the cholesterol content in low-density lipoproteins (LDL-C). These findings have prompted a reconsideration of the biological functions of HDL that can be summarized with the word “HDL functionality”, a term that embraces the many reported biological activities beyond the so-called reverse cholesterol transport, to explain this lack of correlation between HDL levels and CVD. All these aspects are summarized and critically discussed in this review, in an attempt to provide a background scenario for the “HDL story”, a lipoprotein still in search of a role.
Background: The prevention and treatment of obesity and its cardio-metabolic complications are relevant issues worldwide. Among lifestyle approaches, very low-calorie ketogenic diets (VLCKD) have ...been shown to lead to rapid initial weight loss, resulting in better long-term weight loss maintenance. As no information on VLCKD studies carried on in a real-world setting are available, we conducted this multi-centre study in a real-world setting, aiming at assessing the efficacy and the safety of a specific multiphasic VLCKD program in women with overweight or obesity. Methods: A multi-center, prospective, uncontrolled trial was conducted in 33 outpatient women (age range 27–60 y) with overweight or obesity (BMI: 30.9 ± 2.7 kg/m2; waist circumference: 96.0 ± 9.4 cm) who started a VLCKD dietary program (duration: 24 weeks), divided into four phases. The efficacy of VLCKD was assessed by evaluating anthropometric measures and cardiometabolic markers; liver and kidney function biomarkers were assessed as safety parameters. Results: The VLCKD program resulted in a significant decrease of body weight and BMI (−14.6%) and waist circumference (−12.4%). At the end of the protocol, 33.3% of the participants reached a normal weight and the subjects in the obesity range were reduced from 70% to 16.7%. HOMA-IR was markedly reduced from 3.17 ± 2.67 to 1.73 ± 1.23 already after phase 2 and was unchanged thereafter. Systolic blood pressure decreased after phase 1 (−3.5 mmHg) and remained unchanged until the end of the program. Total and LDL cholesterol and triglycerides were significantly reduced by VLCKD along with a significant HDL cholesterol increase. Liver, kidney and thyroid function markers did not change and remained within the reference range. Conclusions: The findings of a multi-center VLCKD program conducted in a real-world setting in a cohort of overweight/obese women indicate that it is safe and effective, as it results in a major improvement of cardiometabolic parameters, thus leading to benefits that span well beyond the mere body weight/adiposity reduction.
Major guidelines recommend the initiation of a beta-blocker therapy after an acute myocardial infarction (AMI). We aimed to map the treatment pathway of beta-blockers for AMI survivors during the ...first wave of COVID-19 pandemic in Italy and to investigate predictors for treatment non-initiation.
Healthcare utilization databases of Lombardy Region were investigated. Subjects aged ≥18 years who were hospitalised with AMI in the period February-March-April of 2018, 2019, and 2020 were included, and followed for 30 days from the discharge date, to investigate whether they presented a first prescription of beta-blockers. A multivariate logistic model was performed to evaluate the effect of several covariates on the probability of not receiving a post-AMI beta-blocker therapy.
The cohorts comprised 2259, 2383, and 1932 individuals who were hospitalised with AMI in the 3-month period in 2018, 2019, and 2020, respectively. Overall in 2020, about 58-60% of individuals with AMI received a prescription of beta-blockers within 1 month after the discharge. A continuous decreasing trend over time was observed. Men were 30% more likely to start the treatment than women, increasing age was associated with significant increasing probability of not receiving a post-infarction beta-blocker therapy, while having received an antihypertensive or lipid-lowering treatment, or having been hospitalized for heart failure prior to the AMI hospitalization reduced the likelihood of not being treated with beta-blockers.
The initiation of beta-blocker treatment after AMI remains an under-prescribed practice, that does not seem to have been further affected by the first wave of the COVID-19 pandemic.
Drugs for peptic ulcer and gastro-esophageal reflux disease (GERD) are among the most widely prescribed, frequently without appropriate indications. This represents an important issue, as it leads to ...risk of adverse events for patients and unnecessary costs for National Health Service.
To assess the prescription appropriateness of drugs for GERD, in the frame of the "Evaluation of the effectiveness of a Low-cost informative intervention to improve the Appropriate PrescripTiOn of Proton PumP Inhibitors in older people in primary care: a cluster-randomized controlled study" (LAPTOP-PPI) (Clinicaltrial.gov: NCT04637750).
The appropriateness of drug prescription was assessed on data collected in administrative databases, by integrating information on concomitant medications, outpatient medical and laboratory procedures and hospital discharge diagnoses, according to the reimbursement criteria provided by the Italian Medicine Agency. We analyzed data of community-dwelling people aged 65 years and over, living in the areas of Bergamo (Northern Italy) and Caserta (Southern Italy), from July 1 to 31 December 2019.
Among 380,218 patients, 175,342 (46.1%) received at least one prescription of drugs for GERD. All in all, we found that only 41.2% of patients received appropriate prescriptions.
Given the potential risk of adverse drug reactions, especially in older people, educational interventions should be prompted for physicians, in order to improve the quality of prescription of drugs for GERD and, in turn, avoid unfavorable health outcomes and unnecessary costs.
Adherence to the Mediterranean diet (MedDiet) is recommended for cardiovascular disease prevention. However, recent epidemiological studies report a shift toward lower adherence to MedDiet. We have ...conducted a prospective cohort study to evaluate changes in individual determinants of MedDiet adherence over time. Clinical information and MedDiet adherence score (MEDAS) were collected in 711 subjects (mean age 68 ± 10 years; 42% males), enrolled in the PLIC study (Progression of Intimal Atherosclerotic Lesions in Carotid arteries), during two visits conducted, on average, 4.5 years apart. MEDAS score worsening and improvements (absolute change, ΔMEDAS) and the variation in the proportion of subjects reporting to meet each MEDAS criteria were assessed. Overall, 34% of the subjects improved their MedDiet adherence (ΔMEDAS: +1.87 ± 1.13), by consuming more olive oil, legumes and fish and use of dishes seasoned with sofrito and 48% subjects worsened their MedDiet adherence (ΔMEDAS: -2.02 ± 1.14) by consuming less fruit, legumes, fish and nuts, with higher rates of worsening in women and subjects aged 50-65 years. Subjects who improved the score were more obese, had higher plasma glucose levels, and metabolic syndrome at the basal visit. In summary, we report an overall decrease in MedDiet adherence, evaluated during a timeframe heavily affected by the COVID-19 pandemic, underlining the need for better dietary interventions.
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