Dyslipidemia is a primary risk factor for cardiovascular disease (CVD). Exercise training (EXTr) improves some lipid markers but not others; the literature is dated and analyses may be underpowered.

To clarify which lipid markers are altered with ExTr and establish if information size had yet reached futility.

We conducted a systematic review/meta-analysis, with meta-regression, to establish expected effect size in lipid profile with aerobic (AT), resistance (RT) and combined (CT = AT + RT) ExTr. We conducted trial sequence analysis (TSA) to control for type I and II error and establish if information size had reached futility.

We included 148 relevant randomized controlled trials (RCTs) of ExTr, with 227 intervention groups, total 8673 participants; exercise 5273, sedentary control 3400. Total cholesterol (TC) MD - 5.90 mg/dL (95% confidence interval (CI) - 8.14, - 3.65), high-density lipoprotein cholesterol (HDL) 2.11 (95% CI 1.43, 2.79), low-density lipoprotein cholesterol (LDL) - 7.22 (95% CI - 9.08, - 5.35), triglycerides - 8.01 (95% CI - 10.45, - 5.58) and very low-density lipoprotein cholesterol (VLDL) - 3.85 (95% CI - 5.49, - 2.22) all showed significant but modest 3.5-11.7%, improvements following ExTr. TSA indicated all analyses exceeded minimum information size to reach futility. CT was optimal for dyslipidemia management. Meta-regression showed every extra weekly aerobic session reduced TC - 7.68 mg/dL and for every extra week of training by - 0.5 mg/dL. Each minute of session time produced an additional 2.11 mg/dL HDL increase.

TSA analysis revealed sufficient data exist to confirm ExTr will improve all five lipid outcomes. CT is optimal for lipid management. The modest effect observed may moderate dyslipidemia medication for primary prevention. Prediction intervals suggest TC, HDL, LDL and TGD are only improved in one-quarter of studies.

Lowering the blood concentration of low-density lipoprotein cholesterol (LDL-C), is a cornerstone in preventing atherosclerotic cardiovascular disease (ASCVD). Current European guidelines recommends LDL-C < 1.4 mmol/L for secondary prevention in high-risk patients. The aim of this study is to investigate monitoring and treatment of hypercholesterolemia one year after a ASCVD event.

Danish patients with hypercholesterolemia and an incident ASCVD event from 2015 to 2020 were included in this nationwide cohort study. Patients' LDL-C measurements and lipid-lowering treatment were followed for one year after ASCVD event, or until death or migration. Imputation was used to estimate absolute LDL-values when patients were unmeasured.

A total of 139,043 patients were included in the study with a mean follow-up time of 10.4 months. During the one-year period, 120,020 (86%) patients had their LDL-C measured at least once, 83,723 (60%) patients were measured at least twice. During the period one to six months after ASCVD event 25,999 (19%) achieved an LDL-C < 1.4 mmol/L, 93,349 (67%) failed to achieve an LDL-C < 1.4 mmol/L, and 196,950 (14%) had died or migrated. Missing LDL-C values were estimated via imputation. At the end of month twelve, 60,583 (44%) patients were in statin monotherapy, 2926 (2%) were treated with other lipid-lowering treatment, 42,869 (31%) were in no treatment, and 32,665 (23%) had died or migrated.

Many Danish patients are not appropriately followed-up with LDL-C measurements, and a substantial number of patients are not in lipid-lowering treatment one year after an ASCVD event.

Lipid-lowering therapy (LLT) in patients with cardiovascular disease (CVD) is insufficient despite clear guideline recommendations. Lipid clinics have specialized in patients with dyslipidemia, but the magnitude and reduction of low-density lipoprotein cholesterol (LDL-C) in lipid clinics has not yet been studied in depth.

To assess LDL-C reduction in very high-risk CVD patients achieved in a lipid clinic through different forms of LLT in comparison to standard care without the initiation of PSCK9 inhibitors.

Data from 96 lipid clinic patients were analyzed retrospectively and compared to 84 standard care patients. Very high-risk patients were defined according to the European Society of Cardiology (ESC). Different combinations of LLT focusing on statins and ezetimibe were investigated. Achievement of LDL-C treatment goals according to ESC guidelines as well as LDL-C reduction were assessed.

Baseline and follow-up data of 180 very high-risk CVD patients (mean age 67.7 (±9.8) y; 60.6% male) were used. Achievement of the LDL-C goal in lipid clinic patients increased significantly from 14.6% at baseline to 41.7% at the latest visit (p<0.001) while standard care patients improved from 21.4% to 33.3% (p=0.08). The largest relative LDL-C reduction via an adjustment in LLT was achieved by initiation of high-intensity statins (50.8 ± 4.9%, n = 5, p < 0.05).

Treatment in a lipid clinic leads to a superior LDL-C goal achievement in very high-risk CVD patients as compared to standard care with the highest reduction under LLT with high-intensity statins and ezetimibe. Referral algorithms have to be established for high-risk patients.

Statins are associated with new-onset type 2 diabetes (T2D), mainly in patients with metabolic syndrome (MetS). The fatty liver index (FLI) is used as a prognostic score for the diagnosis of non-alcoholic fatty liver disease (NAFLD), which is common in patients with MetS. We aimed to investigate the association of FLI with new-onset T2D in patients initiating statin therapy.

A retrospective observational study including 1241 individuals with dyslipidemia and followed up for ≥3 years. Patients with T2D and those receiving lipid-lowering treatment at the baseline visit were excluded. Models with clinical and laboratory parameters were used to assess the association of FLI with incident T2D.

Among the 882 eligible subjects, 11% developed T2D during the follow-up (6 years; IQR: 4-10 years). After adjusting for sex, age and MetS parameters, a multivariate analysis revealed that age (HR:1.05; 95%CI: 1.01-1.09, p < 0.05), fasting plasma glucose (HR: 1.09; 95%CI: 1.06-1.13, p < 0.001) and FLI (HR: 1.02; 95%CI: 1.01-1.04, p < 0.01) were independently associated with T2D risk. The subjects with probable NAFLD (FLI ≥ 60) had a three-fold increased T2D risk compared with the subjects with FLI < 60 (HR: 3.14; 95%CI: 1.50-6.59, p = 0.001). A ROC curve analysis showed that FLI had a significant, although poor, predictive value for assessing T2D risk (C-Statistic: 0.67; 95%CI: 0.58-0.77, p = 0.001). Higher FLI values were associated with reduced T2D-free survival (log-rank = 15.46, p < 0.001).

FLI is significantly and independently associated with new-onset T2D risk in patients initiating statin therapy.

Assess achievement of low-density lipoprotein cholesterol (LDL-C) targets in European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines.

Systematic literature review.

Medline, EMBASE, Cumulated Index to Nursing and Allied Health Literature.

Observational studies reporting LDL-C levels/target attainment, measured between 1 August 2006 to 31 August 2017, in European adults with established cardiovascular disease (CVD), diabetes with target organ damage, familial hypercholesterolaemia (FH) or 10-year risk of fatal CVD ≥ 5% (assessed by Systematic Coronary Risk Evaluation [SCORE]).

Two reviewers independently extracted relevant studies and assessed study quality using the Risk of Bias for Non-Randomised Studies-Interventions (ROBINS-I) tool. Primary outcome was the proportion of patients achieving LDL-C targets in the 2011/2016 ESC/EAS guidelines. Where available, patient characteristics were presented as means weighted by sample size. The proportions of patients achieving LDL-C targets in the 5 years before and after publication of the 2011 guidelines were compared using a chi-square test.

Across 81 eligible studies (303,534 patients), achievement of LDL-C < 1.8 mmol/L was poor among patients with established CVD (16%; range 9-56%) and at very high risk of CVD (SCORE ≥ 10% [18%; 14-25%]). In individuals with FH, SCORE 5-10%, or diabetes and target organ damage, LDL-C < 2.5 mmol/L was achieved by 15% (9-22%), 46% (21-55%) and 13% (6-34%), respectively. Comparing the 5 years before/after publication of the 2011 guidelines, target achievement increased significantly over time but remained suboptimal (LDL-C < 1.8, 22% versus 15%; LDL-C < 2.5, 68% versus 61%; both p < 0.001; established CVD group only).

These data show suboptimal LDL-C control among European patients at high risk of CVD. Those at greatest overall risk (clinically established CVD or at least a 10% 10-year risk of fatal CVD) had the lowest achievement of 2011/2016 EAS/ESC LDL-C targets. With lower LDL-C targets advocated in 2019 ESC/EAS guidelines, this unmet need will increase.

PROSPERO registration number; CRD77844.

This study compares two methods of providing CVD risk score on the percentage of appropriate statin therapy for primary prevention of CVD in family medicine clinics, according to the American Heart Association guidelines.

Participants were non-diabetic patients aged 40 to 75 with a recently ordered low-density lipoprotein (LDL) level, not on statin therapy and free of CVD. The first intervention is passive with a display of the score on the EMR in the vital signs section and lasted for three months. The second intervention is collaborative where the nurses calculate the risk score and displayed it to the physician along with therapy recommendations. Electronic health records were reviewed to randomly select medical charts of eligible patients.

162 charts were randomly selected out of 547 eligible charts and included in the analysis, including 60 charts for the baseline group. Among moderate-risk patients, the percentage of appropriate statin initiation was 0% at baseline and after intervention 1; yet it increased to (33.3% [7.5-70.1, 95% CI]) after intervention 2. Among high risk patients, percentage of appropriate statin initiation was 9.1% [0.1-41.3, 95% CI], 11.1% [1.4, 34.7, 95% CI] and 28.6% [8.4, 58.1, 95% CI] during baseline, intervention 1 and intervention 2, respectively.

The provision of the CVD risk score alone as clinical decision support is not enough to improve statin initiation for primary prevention. The nurse collaboration can improve guideline-concordant statin initiation.

Elevated uric acid (UA) is a recognized risk factor for chronic kidney disease (CKD). This study aimed to investigate whether this association exists in dyslipidemic patients receiving multifactorial treatment.

An observational study conducted in Greece including 1,269 dyslipidemic individuals followed-up in a lipid clinic for ≥3 years. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI equation and CKD was defined as ≤60 mL/min/1.73 m². The correlation was assessed between UA levels and the CKD risk after adjusting for potential confounding factors, after defining the following UA quartiles: Q1: < 4, Q2: 4-5, Q3: 5-6, and Q4: > 6 mg/dL.

After excluding patients with baseline eGFR <60 mL/min/1.73 m², gout and those taking UA-lowering drugs, 1,095 individuals were eligible; of those, 91% and 69% were treated with statins and anti-hypertensive drugs, respectively. During their follow-up (6 years; IQR = 4-10), 11.9% of the subjects developed CKD, whereas the median annual eGFR decline was 0.69 mL/min/1.73 m² (IQR = 0.45-2.33). Multivariate analysis showed that baseline UA levels (HR = 1.26; 95% CI = 1.09-1.45, p = .001), female gender (HR = 1.74; 95% CI = 1.14-2.65, p = .01), age (HR = 1.10; 95% CI = 1.07-1.12, p < .001), diabetes (HR = 1.67; 95% CI = 1.05-2.65, p = .03), cardiovascular disease (HR = 1.62; 95% CI = 1.02-2.58, p = .04), decreased baseline renal function (eGFR <90 mL/min/1.73 m²) (HR = 2.38; 95% CI = 1.14-4.81, p = .02), and low-density lipoprotein cholesterol reduction (HR = 0.995; 95% CI = 0.991-0.998, p = .01) were associated with incident CKD. Additionally, patients with UA ≥6 mg/dL exhibited a higher risk of incident CKD compared with those in the lowest UA quartile (HR = 2.01; 95% CI = 1.11-3.65, p = .02).

Higher UA levels are correlated with a higher risk of incident CKD in dyslipidemic individuals taking multifactorial treatment.

Routinely fasting is not necessary for measuring the lipid profile according to the latest European consensus. However, LDL-C tends to be lower in the non-fasting state with risk of misclassification. The extent of misclassification in secondary cardiovascular prevention with a non-fasting lipid profile was investigated.

329 patients on lipid lowering therapy for secondary cardiovascular prevention measured a fasting and non-fasting lipid profile. Cut-off values for LDL-C, non-HDL-C and apolipoprotein B were set at <1.8mmol/l, <2.6mmol/l and <0.8g/l, respectively. Study outcomes were net misclassification with non-fasting LDL-C (calculated using the Friedewald formula), direct LDL-C, non-HDL-C and apolipoprotein B. Net misclassification <10% was considered clinically irrelevant. Mean age was 68.3±8.5years and the majority were men (79%). Non-fasting measurements resulted in lower LDL-C (-0.2±0.4mmol/l, P<0.001), direct LDL-C (-0.1±0.2mmol/l, P=0.001), non-HDL-C (-0.1±0.4mmol/l, P=0.004) and apolipoprotein B (-0.02±0.10g/l, P=0.004). 36.0% of the patients reached a fasting LDL-C target of <1.8mmol/l with a significant net misclassification of 10.7% (95% CI 6.4-15.0%) in the non-fasting state. In the non-fasting state net misclassification with direct LDL-C was 5.7% (95% CI 2.1-9.2%), 4.0% (95% CI 1.0-7.4%) with non-HDL-C and 4.1% (95% CI 1.1-9.1%) with apolipoprotein B.

Use of non-fasting LDL-C as treatment target in secondary cardiovascular prevention resulted in significant misclassification with subsequent risk of undertreatment, whereas non-fasting direct LDL-C, non-HDL-C and apolipoprotein B are reliable parameters.

To evaluate the presence of the so called "statin escape" phenomenon among hyperlipidemic subjects attending a lipid clinic.

This was a retrospective analysis of 1240 hyperlipidemic individuals followed-up for ≥ 3 years. We excluded those individuals meeting one of the following criteria: Use of statin therapy at baseline visit, discontinuation of statin treatment at most recent visit, change in statin treatment during follow-up and poor compliance to treatment. Statin escape phenomenon was defined as an increase in low-density lipoprotein cholesterol (LDL-C) levels at the most recent visit by > 10% compared with the value at 6 mo following initiation of statin treatment.

Of 181 eligible subjects, 31% exhibited the statin escape phenomenon. No major differences regarding baseline characteristics were found between statin escapers and non-statin escapers. Both escapers and non-escapers had similar baseline LDL-C levels [174 (152-189) and 177 (152-205) mg/dL, respectively]. In comparison with non-escapers, statin escapers demonstrated lower LDL-C levels at 6 mo after treatment initiation [88 (78-97) mg/dL vs 109 (91-129) mg/dL, P < 0.05], but higher levels at the most recent visit [103 (96-118) mg/dL vs 94 (79-114) mg/dL, P < 0.05].

These data confirm the existence of an escape phenomenon among statin-treated individuals. The clinical significance of this phenomenon remains uncertain.

Prior studies conducted in Greece consistently indicate that dyslipidemia is suboptimally managed, while the burden of cardiovascular disease (CVD) and related risk factors is rising.

CHALLENGE was a multicenter, cross-sectional study carried out following the publication of guidelines advocating stricter low-density lipoprotein cholesterol (LDL-C) targets. It primarily aimed to depict LDL-C target attainment, and to assess the cardiovascular risk status and quality of life (QoL) of patients treated in a primary or secondary CVD prevention setting who had received any medical intervention for cardiovascular risk modification within 6months of enrollment.

Between December 2012 and April 2013, 500 patients (55% males) aged (mean±SD) 62.0±11.7years, participated in the study. Cardiovascular risk according to the 2011 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines was 'very high', 'high', and 'moderate' in 61.2%, 23.4%, and 15.4%, respectively. Overall, 92.0% of patients were on lipid-lowering treatment, yet only 23.3% had attained their ESC/EAS-defined LDL-C target. LDL-C target attainment was more likely among 'moderate' versus 'very high' cardiovascular risk patients (odds ratio: 4.04; 95% confidence interval: 2.32-7.06; p<0.001). QoL improved as cardiovascular risk decreased (EQ-VAS 71.8±16.2 in the 'very high' versus 78.3±15.1 and 80.3±15.7 in the 'high' and 'moderate' risk groups; p<0.001). Time constraints and difficulties in implementation in daily practice were the investigator's main barriers for guideline utilization.

During contemporary management of dyslipidemia in Greece, LDL-C target attainment is suboptimal. There is an undoubted need for improvement and implementation of cardiovascular risk assessment in routine clinical practice.

To assess the correlation of Apolipoprotein B (Apo-B) with low-density (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) in untreated individuals attending a lipid clinic.

This was a retrospective study conducted in Greece and including 1000 dyslipidemic subjects. We included individuals not taking lipid-lowering therapy at baseline visit and divided them in 2 groups: subjects diagnosed with diabetes or fulfilling the criteria of metabolic syndrome (MetS) and hyperlipidemic subjects without diabetes or MetS. The correlations (r(2)) of Apo-B with LDL-C and non-HDL-C were assessed in these 2 groups. Further analyses were performed according to the baseline triglyceride (TG) levels (<and ≥200 mg/dL).

From 821 eligible subjects, 51% were diagnosed with diabetes or MetS. The correlations between Apo-B and LDL-C or non-HDL-C were similar for the individuals with TG < 200 mg/dL. Specifically, Apo-B was significantly correlated with LDL-C (r(2) = 0.755, p < 0.01, for those with diabetes or MetS; r(2) = 0.848, p < 0.01, for non-diabetic and no MetS hyperlipidemic subjects). The corresponding correlations between Apo-B and non-HDL-C for the 2 groups were 0.743 and 0.838, respectively (p < 0.01). Although these correlations remained significant for the individuals with high TG levels (≥200 mg/dL), the correlation factor was markedly decreased mostly in those with diabetes or MetS (r(2) = 0.600, p < 0.01, for the correlation between Apo-B and LDL-C; r(2) = 0.604, p < 0.01, for the correlation between Apo-B and non-HDL-C); in contrast, the corresponding correlations were stronger in the non-diabetic and no MetS hyperlipidemic individuals (r(2) = 0.710 and 0.714, respectively, p < 0.01).

Apo-B correlation with both LDL-C and non-HDL-C is reduced in individuals with high TG levels and in particular for those with diabetes or MetS.

To assess the risk of progression from normoglycemia or prediabetes to overt diabetes among individuals treated with statins alone or in combination with ezetimibe.

This was a retrospective study conducted in Greece including 877 subjects treated for dyslipidemia. We included individuals without overt diabetes at baseline and divided them in 2 subgroups according to their baseline fasting glucose: <100 (normal glucose) and 100 to 125 mg/dL (prediabetes). High and moderate-intensity statin therapy was defined according to the expected low-density lipoprotein cholesterol reduction (≥50% and 30 to <50%, respectively). We identified the predictors of incident diabetes and assessed the risk of new-onset diabetes among subgroups on various intensity statin or no statin treatment at all. Similar analyses were performed across different potency of statin monotherapy or combination of statin plus ezetimibe treatment.

A total of 877 subjects were eligible and followed-up for a median of 7 years. There were no differences between statins regarding diabetes development. However, a higher risk of incident diabetes was observed in prediabetic individuals receiving high-intensity statin therapy compared with those on moderate intensity (adjusted odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.06-4.24, P < .05) and those not taking a statin (adjusted OR = 4.90; 95% CI = 1.16-20.66, P < .05). The addition of ezetimibe to statin treatment did not increase the risk of incident diabetes in prediabetic individuals (adjusted OR = 0.89; 95% CI = 0.36-2.22, P > .05). Baseline fasting glucose, presence of metabolic syndrome, family history of diabetes, and follow-up duration were independent predictors of new-onset diabetes.

High-intensity statin treatment is associated with a higher risk of incident diabetes in prediabetic individuals, whereas the addition of ezetimibe to statin therapy has a neutral effect on glucose metabolism.

Familial hypercholesterolemia (FH) is undoubtedly associated with premature coronary heart disease, but it is debatable whether FH increases the risk for stroke.

To meta-analyze available evidence regarding the incidence of stroke in individuals with heterozygous (He) FH.

We conducted a systematic review and a meta-analysis of epidemiological studies, including English-language publications until June 2015; four observational studies, with 3374 participants with HeFH, were included in the analysis. Cerebrovascular disease comprised of ischemic stroke or transient ischemic attack. Since studies did not include any control subjects, the corresponding general population of the same reference area and period of time for each HeFH study served as control group. Analyses were performed according to the period of time during which the studies were conducted: prestatin and statin era (before and after 1987 when lovastatin was launched).

In the prestatin era, individuals with HeFH exhibited a higher risk for stroke compared with the general population [odds ratio (OR) = 7.658, 95% confidence interval (CI): 6.059-9.678, p < 0.01]. In contrast, FH subjects had a lower odds for stroke following the generalization of statin therapy (OR = 0.251, 95% CI: 0.176-0.358, p < 0.01).

Taking into account the small number of studies and methodological issues, HeFH was associated with a higher risk of cerebrovascular disease compared with the general population in the prestatin era, which was significantly reduced after the introduction of statin therapy.

To examine target attainment of lipid-lowering, antihypertensive and antidiabetic treatment in the elderly in a specialist setting of a University Hospital in Greece.

This was a retrospective study including consecutive subjects ≥ 65 years old (n = 465) with a follow-up ≥ 3 years. Low-density lipoprotein cholesterol (LDL-C), blood pressure (BP) and glycated hemoglobin (HbA1c) goal achievement were recorded according to European Society of Cardiology/European Atherosclerosis Society (ESC/EAS), European Society of Hypertension (ESH)/ESC and European Association for the Study of Diabetes (EASD) guidelines.

The LDL-C targets were attained by 27%, 48% and 62% of very high, high and moderate risk patients, respectively. Those receiving statin + ezetimibe achieved higher rates of LDL-C goal achievement compared with those receiving statin monotherapy (48% vs. 33%, P < 0.05). Of the diabetic subjects, 71% had BP < 140/85 mmHg, while 78% of those without diabetes had BP < 140/90 mmHg. A higher proportion of the non-diabetic individuals (86%) had BP < 150/90 mmHg. Also, a higher proportion of those with diabetes had HbA1c < 8% rather than < 7% (88% and 47%, respectively). Of note, almost one out of three non-diabetic individuals and one out of ten diabetic individuals had achieved all three treatment targets.

Even in a specialist setting of a University Hospital, a high proportion of the elderly remain at suboptimal LDL-C, BP and HbA1c levels. The use of drug combinations could improve multifactorial treatment target attainment, while less strict targets could be more easily achieved in this population.