Central and Eastern Europe (CEE) is a largely understudied region, despite having the highest cardiovascular disease mortality in Europe. This analysis aimed to assess the proportion of patients in CEE who achieved their LDL-C goals based on individual cardiovascular risk recommended by the 2016 and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines.

The DA VINCI study was a cross-sectional observational study of primary and secondary prevention patients receiving lipid-lowering therapy across Europe between June 2017 and November 2018.

In total, 2154 patients were enrolled from the Czech Republic (n = 509), Hungary (n = 319), Poland (n = 460), Romania (n = 259), Slovakia (n = 123) and Ukraine (n = 484). At LDL-C measurement, most patients were on either moderate- or high-intensity statin monotherapy (53% and 32%, respectively). Despite this, only 44% of patients achieved risk-based LDL-C goals recommended by the 2016 ESC/EAS guidelines, ranging from 21% in Ukraine to 50% in Hungary and Romania. Only 24% of patients overall achieved the risk-based LDL-C goals recommended by the 2019 ESC/EAS guidelines, ranging from 11% in Ukraine to 32% in Poland.

Among patients receiving lipid-lowering therapy, more than half did not achieve their 2016 LDL-C goals. In one of the first comparative analyses evaluating 2019 risk-based goal attainment among countries in CEE, three-quarters of patients did not meet their 2019 LDL-C goals, highlighting a significant gap between guidelines and clinical practice for lipid management in CEE.

Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I).

Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl^-1 (men) or ≤50 mg dl^-1 (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42.

The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l^-1 , 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl^-1 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl^-1 , 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl^-1 , 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 μg ml^-1 , 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity.

The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.

During phylogenesis, all fatty acids (FA) were initially transported to cells by apoA-I high-density lipoproteins (HDL) in polar lipids. Later, active cellular uptake of saturated, monoenoic and unsaturated FA occurred via triglycerides (TG) in low-density lipoproteins (LDL). Active uptake of polyenoic FA (PUFA) required the following: a) PUFA re-esterified from polar phospholipids into nonpolar cholesteryl polyesters (poly-CLE), b) a novel protein, cholesteryl ester transfer protein (CETP), initiated poly-CLE transformation from HDL to LDL. CETP formed blood HDL-CETP-LDL complexes in which poly-CLE spontaneously came from polar lipids of TG in HDL to nonpolar TG in LDL. Then ligand LDLs formed and the cells actively absorbed PUFA via apoB-100 endocytosis. Some animal species (rats, mice, dogs) developed a spontaneous CETP-minus mutation followed by population death from atherosclerosis. However, there was another active CETP-independent uptake formed during phylogenesis; the cells internalized poly-CLE in HDL. Since apoA-I had no domain-ligand, another apoE/A-I ligand formed; the cells began synthesizing apoE/A-1 receptors. In cells of rabbits and primates absorbed cells PUFA consecutively: HDL-->LDL-->apoB-100 endocytosis; those of rats and dogs did HDL directly: HDL-->anoE/A-I endocytosis. In the rabbits, CETP was high, apoE in HDL was low, and the animals were sensitive to exogenous hypercholesterolemia. In the rats, CETP was low and ApoE in HDL-was high, and the animals were resistant to hypercholesterolemia. Reduced bioavailability of PUFA during their consecutive cellular uptake and develdpment of intercellular PUFA deficiency are fundamental to the pathogenesis of atherosclerosis.

Dyslipidemia is a common contributory cause of cardiovascular disease. Vaccinium arctostaphylos L. (Caucasian whortleberry) fruit is rich of anthocyanins. Anthocyanins may exert cardioprotective effects by various mechanisms such as favorably modulating dyslipidemia. Therefore, in this randomized double-blind placebo-controlled clinical trial with hyperlipidemic (hypercholesterolemic and/or hypertriglyceridemic) patients aged 20-60 years, the effects of taking a standardized whortleberry fruit hydroalcoholic extract (one 350 mg capsule every 8 h for 2 months) on fasting blood levels of lipids, creatinine and liver enzymes including SGOT and SGPT were evaluated in 40 patients and compared with the placebo group (n = 40). The extract lowered the blood levels of total cholesterol (P < 0.001), triglyceride (P = 0.002) and low-density lipoprotein cholesterol (LDL-C) (P = 0.002), but increased the blood high-density lipoprotein cholesterol (HDL-C) levels (P < 0.001) without any significant effects on the blood levels of SGOT, SGPT and creatinine (P > 0.05) compared with the placebo group at the endpoint. Whortleberry reduced total cholesterol, triglyceride and LDL-C 27.6%, 19.2% and 26.3%, respectively, but increased HDL-C 37.5% compared with baseline. No adverse effects were reported. Short-term treatment with whortleberry fruit appears safe and improves lipid profile in hyperlipidemic patients.

With the advent of highly active antiretroviral therapy (HAART), Cardiovascular Disease (CVD) has emerged as the leading cause of death in Human Immunodeficiency Virus (HIV) infected patients. An atherogenic lipoprotein phenotype has been described in HIV- infected patients with a predominance of small, low density lipoprotein (SLDL) particles with accompanying elevated triglycerides and reduced high density lipoprotein cholesterol. This randomized controlled pilot study was conducted to evaluate the efficacy of Extended Release Niacin (ERN) in improving the lipid profile in HIV patients. A total of 17 HIV positive subjects on HAART therapy with High Density Lipoprotein Cholesterol (HDL) levels below 40mg/dl and Low Density Lipoprotein Cholesterol (LDL) below 130mg/dl were enrolled. Nine were randomized to be treated with ERN titrated from a starting level of 500mg/night and titrated to a level of 1500mg/night. Eight patients were assigned to the control arm. No placebo was used. Lipoprotein profiles of the subjects were analyzed at baseline and at the end of 12 weeks using Nuclear Magnetic Resonance (NMR) spectroscopy. At the end of 12 weeks, NMR spectroscopic analysis revealed a significant increase in overall LDL size (1.2% in ERN treated subjects vs 2.0% decrease in control patients, P=.04) and a decrease in small LDL particle concentration (17.0% in ERN treated subjects vs 21.4% increase in control patients, P=.03) in subjects receiving ERN as compared to those in the control group. Only 1 subject receiving ERN developed serious flushing which was attributed to an accidental overdose of the drug. This pilot study demonstrates that ERN therapy in HIV-infected patients with low HDL is safe and effective in improving the lipoprotein profile in these patients.

Hyperlipidemia is a common metabolic disorder contributing to morbidities and mortalities due to cardiovascular and cerebrovascular diseases. Conventional antihyperlipidemic drugs have limited efficacies and important side effects, so that alternative lipid lowering agents are needed. Salvia officinalis L. (sage) leaves have PPAR γ agonistic, pancreatic lipase and lipid absorption inhibitory, antioxidant, lipid peroxidation inhibitory and antiinflammatory effects. Thus, in this randomized double-blind placebo-controlled clinical trial with 67 hyperlipidemic (hypercholesterolemic and/or hypertriglyceridemic) patients aged 56.4 ± 30.3 years (mean ± SD), the effects of taking sage leaf extract (one 500 mg capsule every 8 h for 2 months) on fasting blood levels of lipids, creatinine and liver enzymes including SGOT and SGPT were evaluated in 34 patients and compared with the placebo group (n = 33). The extract lowered the blood levels of total cholesterol (p < 0.001), triglyceride (p = 0.001), LDL (p = 0.004) and VLDL (p = 0.001), but increased the blood HDL levels (p < 0.001) without any significant effects on the blood levels of SGOT, SGPT and creatinine (p > 0.05) compared with the placebo group at the endpoint. No adverse effects were reported. The results suggest that sage may be effective and safe in the treatment of hyperlipidemia.

Despite the use of currently available lipid-lowering therapies, a significant proportion of patients with severe hypercholesterolaemia do not reach treatment goals and consequently remain at increased risk for cardiovascular disease (CVD). On the basis of clinical experience, these patients tend to have the most severe forms of familial hypercholesterolaemia or markedly elevated LDL cholesterol (LDL-C) levels but are unable to tolerate statin therapy.

LDL apheresis is currently the best treatment option (or treatment rescue) to bring these patients closer to therapeutic LDL objectives, and has been shown to reduce the risk of CVD along with LDL-C levels. However, criteria for LDL apheresis eligibility and the percentage of patients receiving treatment vary widely from country to country across Europe. Despite the proven benefits of LDL apheresis, access to this procedure remains limited because of its high cost and low availability, reflecting inherent limitations of this treatment modality.

There is a need to both better define the patient population eligible for LDL apheresis and to create unified European guidelines governing the use of apheresis. In addition to improving access to apheresis where appropriate, new therapies are needed to further decrease LDL-C and reduce the ongoing CVD risk in patients with severe hypercholesterolaemia.

Because of methodological limitations and conflicting results of studies conducted thus far, the possible involvement of human adipose tissue in pleiotropic effects of statins and fibrates requires better understanding. Samples of visceral and subcutaneous adipose tissue obtained from 23 mixed dyslipidemic patients and 23 normolipidemic subjects were treated in vitro for 48 h with atorvastatin, fenofibric acid or both these agents. Visceral and subcutaneous fat of mixed dyslipidemic patients released more leptin, resistin, interleukin-6, tumor necrosis factor alpha (TNFalpha and plasminogen activator inhibitor-1 (PAI-1), and less adiponectin than respective adipose tissue of patients without lipid abnormalities. In both groups of patients, visceral and subcutaneous tissue varied in the amount of secreted adipokines. In dyslipidemic patients both drugs administered alone affected adipose tissue adiponectin and resistin secretion. Additionally, atorvastatin decreased PAI-1 while fenofibric acid reduced leptin release. A combined administration of atorvastatin and fenofibric acid changed the release of all studied markers by visceral fat but did not affect interleukin-6 and TNFalpha release by subcutaneous tissue. In normolipidemic subjects the effect on adipokine release was more pronounced in visceral fat, in which it was strongest if the drugs were given together. Adipose tissue hormonal activity differs between mixed dyslipidemic and normolipidemic patients and between visceral and subcutaneous adipose tissue. Atorvastatin and fenofibrate exhibit their pleiotropic effects in part by changing the adipokine release by human adipose tissue, regardless of its origin. These effects are stronger in patients with mixed dyslipidemia and are particularly pronounced if atorvastatin and fenofibric acid are given together.

Although statin therapy represents a cornerstone of cardiovascular disease (CVD) prevention, a major residual CVD risk (60-70% of total relative risk) remains, attributable to both modifiable and non-modifiable risk factors. Among the former, low levels of HDL-C together with elevated triglyceride (TG)-rich lipoproteins and their remnants represent major therapeutic targets. The current pandemic of obesity, metabolic syndrome, and type 2 diabetes is intimately associated with an atherogenic dyslipidemic phenotype featuring low HDL-C combined with elevated TG-rich lipoproteins and small dense LDL. In this context, there is renewed interest in pharmacotherapeutic strategies involving niacin and fibrates in monotherapy and in association with statins. This comprehensive, critical review of available data in dyslipidemic subjects indicates that niacin is more efficacious in raising HDL-C than fibrates, whereas niacin and fibrates reduce TG-rich lipoproteins and LDL comparably. Niacin is distinguished by its unique capacity to effectively lower Lp(a) levels. Several studies have demonstrated anti-atherosclerotic action for both niacin and fibrates. In contrast with statin therapy, the clinical benefit of fibrates appears limited to reduction of nonfatal myocardial infarction, whereas niacin (frequently associated with statins and/or other agents) exerts benefit across a wider range of cardiovascular endpoints in studies involving limited patient numbers. Clearly the future treatment of atherogenic dyslipidemias involving the lipid triad, as exemplified by the occurrence of the mixed dyslipidemic phenotype in metabolic syndrome, type 2 diabetes, renal, and auto-immune diseases, requires integrated pharmacotherapy targeted not only to proatherogenic particles, notably VLDL, IDL, LDL, and Lp(a), but also to atheroprotective HDL.

Cardiovascular disease (CVD) continues to be a leading cause of death worldwide. Elevated serum cholesterol is one of the classical risk factors for CVD, which also include age, hypertension, smoking, diabetes mellitus, obesity and family history. Several therapeutic drug classes have been developed to treat hypercholesterolemia; yet, an important percentage of patients do not reach their treatment goals. Therefore, new cholesterol-lowering medications that have sites of action different from that of drugs available at present need to be developed. This review summarizes new information about cytochrome P450 enzymes 7A1, 27A1 and 46A1. These enzymes play key roles in cholesterol elimination and have the potential to serve as targets for cholesterol-lowering.

Lipid management in UK general practice targets the achievement of total cholesterol (TC) targets in high-risk individuals. Statins alone have a modest effect on non-LDL-C components of the lipid profile, leaving these patients at significant residual cardiovascular (CV) risk. Improving risk further would require the addition of non-statin therapies. This analysis explores what proportion of the UK population with cardiovascular disease (CVD) and TC levels at or below target may still be at risk because of residual dyslipidaemia.

CV risk profiles were extracted from a research database of 602,222 patients from 98 UK general practices. Patients were categorised according to their prior CV history and use of statins. Mean values and proportions achieving treatment targets were assessed for TC, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) and triglycerides (TG).

In all, 48 499 patients with pre-existing CVD or diabetes were identified. 73% of statin-treated patients and 63% of untreated patients had a TC < or =5 mmol/L. 28.6% of patients treated to a TC target had LDL-C>3 mmol/L. Amongst those with both TC and LDL-C treated to target, 22.5% had low HDL-C and 37.2% had high triglyceride (TG). Within this group, more women than men had abnormal HDL-C (25.4 vs. 20.7%; p<0.0001). Patients with diabetes were more likely than non-diabetics to have abnormalities of both HDL-C (28.9 vs. 16.4%; p<0.0001) and triglyceride (44.9 vs. 29.5%; p<0.0001) despite normal TC and LDL-C.

Around 60% of high-risk patients have residual dyslipidaemias despite achieving the Quality and Outcomes Framework (QOF) TC target. New patterns of treatment are required in order to extend lipid management beyond simple total cholesterol lowering.

Reduction in total cholesterol (TC) and LDL-cholesterol (LDL-C) forms one of the principal objectives of most cardiovascular secondary prevention strategies. Many patients being treated with statins, however, have significant residual dyslipidaemia, with many having suboptimal HDL-cholesterol (HDL-C) levels. The addition of nicotinic acid to a statin has been shown to improve this profile, although clinical outcome evidence is currently lacking. This study set out to model the impact of nicotinic acid therapy on cardiovascular risk in these patients, based on Framingham risk assessments on a cohort of patients drawn from UK general practitioner records.

Cardiovascular risk profiles were extracted from a research database of 602,222 patients from 98 UK general practices. 23 262 statin-treated patients with established cardiovascular disease or diabetes were identified and their 4-year Framingham risk was estimated. Patients who had either TC or HDL-C outside the desirable range then had their lipid profile adjusted in accordance with the likely performance of nicotinic acid, and the Framingham risk was then re-assessed.

Baseline 4-year coronary risk in the group as a whole was 11.5% (95%CI: 11.4-11.6). After adjustment of the lipid profile, this was reduced to 9.7% (95%CI: 9.6-9.8), a reduction in risk of 15.9% (95%CI: 15.1-16.6). When modelling was limited to those with diabetes or an abnormal treated lipid profile, the magnitude of change was increased to 23-29% depending on sex and subgroup.

Risk factor modelling suggests that raising HDL-C levels using nicotinic acid in statin-treated patients is likely to yield significant incremental clinical benefits. The results of clinical trials currently under way are awaited with interest.

The prominent use of fibric acid derivatives has lessened over the years because of unimpressive results in major clinical trials, safety concerns, and the emergence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Clofibrate was widely used in the 1970s, but after publication of results from two major trials demonstrating only modest reductions in the rate of coronary heart disease (CHD) and concerns regarding an increase in the frequency of gallstones and overall mortality, its use subsided dramatically. With the introduction of gemfibrozil in the 1980s came a renewed interest in the class, which was also supported by the published results of the Helsinki Heart Study; however, despite a significant reduction in CHD events and a sound safety profile, overall mortality was comparable to that with placebo. Again, in the 1990s, awareness of the fibrates was heightened with the availability of fenofibrate and the findings of another major trial using gemfibrozil, the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT), which demonstrated impressive results in reducing cardiovascular events. To further strengthen the VA-HIT results, numerous post hoc analyses were performed on the data of major trials of fibrate therapy among patients with mixed dyslipidemia, with similar findings. Recently, however, data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were published, indicating mixed results. Nearly 40 years after the introduction of the fibrates, practitioners are still contemplating the role of these agents in the treatment of CHD.