Reduced Serum Vitamin D Levels Are Associated with Insulin Resistance in Patients with Obstructive Sleep Apnea Syndrome.

Background and objectives: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular and metabolic risk factors, such as insulin resistance. Furthermore, OSAS has been associated with decreased levels of vitamin D (Vit D). The aim of the study was to assess the association between Vit D levels (expressed as 25(OH)D serum levels) and insulin resistance in patients with OSAS. Materials and Methods: Serum 25(OH)D levels were measured in consecutive subjects who had undergone polysomnography and pulmonary function testing. OSAS patients were divided into those with (homeostatic model assessment [HOMA-IR] ≥ 2) and without insulin resistance (HOMA-IR < 2). Results: Overall, 92 patients (81 males) were included in the study. OSAS patients with insulin resistance significantly differed from those without insulin resistance in terms of the body-mass index (BMI) (36.3 ± 5.8 compared to 32 ± 5.6 kg/m2, respectively, p = 0.001), apnoea-hypopnoea index (AHI) (57.4 ± 28.9 compared to 40.9 ± 27.9 events/h, respectively, p = 0.009) and indices of hypoxia during sleep. Patients with OSAS and insulin resistance had lower levels of serum 25 (OH) D compared with OSAS but without insulin resistance (19.3 ± 11.5 vs 26.7 ± 12.2 ng/mL, respectively, p = 0.005). Regression analysis demonstrated a negative association of 25(OH)D levels (ß = -0.048, odds ratio [OR]: 0.953, 95% confidence interval [CI]: 0.913-0.995, p = 0.030) and a positive association of BMI (ß = 0.110, OR: 1.116, 95% CI: 1.007-1.237, p = 0.036) with insulin resistance. Conclusions: Vit D insufficiency was significantly more frequent among OSAS patients with insulin resistance. Both low 25(OH)D levels and high BMI were associated with the risk of insulin resistance in this population.

Pleiotropic effects of proprotein convertase subtilisin/kexin type 9 inhibitors?

PURPOSE OF REVIEW: Current data suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may affect many metabolic pathways beyond lowering LDL cholesterol. The aim of the present manuscript is to present these so-called pleiotropic effects of PCSK9 inhibitors. RECENT FINDINGS: PCSK9 may affect the activity of other receptors beyond LDL receptors (LDLR), such as cluster of differentiation 36 (CD36), very-low-density-lipoprotein (VLDL) receptors, apolipoprotein (Apo) E receptors, LDLR-related protein 1 (LRP-1) and ATP-Binding Cassette Transporter (ABCA1). Thus, a role of PCSK9 in the development of atherosclerosis, in vascular wall inflammation and in platelet function has been suggested. Additionally, PCSK9 inhibitors may affect lipid variables beyond LDL cholesterol, carbohydrate variables, as well as they may affect brain and kidney function. Additionally, a controversial role of PCSK9 in sepsis, hepatitis C infection and Alzheimer's disease has been suggested. SUMMARY: These possible pleiotropic effects of PCSK9 inhibitors need further research, as they may affect cardiovascular risk and provide further insights in the development of atherosclerosis and other diseases such as Alzheimer's disease or chronic viral infection and sepsis.

Treatment of Hypertension in Chronic Kidney Disease.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is recognized as a worldwide epidemic. Hypertension commonly coexists with CKD and its prevalence is progressively increasing as kidney function declines. RECENT FINDINGS: For patients with established CKD and/or diabetes with albuminuria, the updated hypertension guidelines have recommended a blood pressure (BP) goal < 130/80 mmHg. Blood pressure level above 130/80 mmHg in CKD patients requires lifestyle modifications and multiple antihypertensive medications. According to recent guidelines, angiotensin-converting enzyme (ACE) inhibitors should be the drugs of first choice. Angiotensin II receptor blockers (ARBs) should be used if the ACE inhibitor is not tolerated. Non-dihydropyridine CCBs consistently reduce albuminuria and slow the decline in kidney function. Dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD patients but always in combination with a RAAS blocker. Diuretics are commonly used and represent the cornerstone in the management of CKD patients. All the other agents are used when treatment with the other primary agents have failed. In patients with CKD, an intensive BP goal < 130/80 mmHg has been recommended. We review current treatment options.

NMR-Based Lipid Profiling of High Density Lipoprotein Particles in Healthy Subjects with Low, Normal, and Elevated HDL-Cholesterol.

Recent studies suggest that the cholesterol content of HDL (high density lipoproteins) may provide limited information on their antiatherogenic properties and that the composition and particles' structure provide more information on their functionality. We used NMR-based (nuclear magnetic resonance-based) lipidomics to study the relationships of serum HDL-C (HDL-cholesterol) levels with the lipid composition of HDL particles in three groups of subjects selected on the basis of their HDL-C levels. Subjects with low and high HDL-C levels exhibited differences in HDL lipidome compared to those with normal HDL-C levels. In pattern recognition analysis, the discrimination power among all groups was of high significance. The low HDL-C group presented enrichment of the core in triglycerides and depletion in cholesterol esters, whereas the high HDL-C group showed a decrease in triglycerides content. Additionally, as HDL-C increases, all lipid classes are esterified with higher percentage of unsaturated than saturated fatty acids. In addition to the aforementioned differences, the surface layer is enriched in sphingomyelin and free cholesterol in the high HDL-C level group. NMR-based lipidomic analysis of HDL can be particularly useful since it provides insights into molecular features and helps in the characterization of the atheroprotective function of HDL lipoproteins and in the identification of novel biomarkers of cardiovascular risk.

Statins and mortality: the untold story.

Statins are first-line evidence-based drugs for the management of dyslipidaemias and to reduce the risk of cardiovascular events. However, statin clinical trials have shown marginally significant benefits on mortality, especially in the primary prevention setting. A major limitation of those trials is their relatively short follow-up. A reduced number of fatal events within a 5-year follow-up make mortality benefits unlikely to arise. This is particularly relevant for the primary prevention trials, where the risk of cardiovascular death is low. The short follow-up is a limitation for safety assessments too. However, extended major statin trials failed to detect any major safety concerns. Safety and efficacy assessments are even more complicated considering the differences of cardiovascular risk status in primary prevention individuals, and also given some potential ethnic and inter-individual genetic variations in response to statin treatment. Considerable evidence suggests a favourable risk-benefit balance for statin treatment. It can be assumed that statins reduce mortality in the long term by preventing cardiovascular events with complications that reduce lifespan. Unfortunately, this hypothesis cannot be proven as there is no current ethical basis on designing long-term placebo-controlled statin trials. Nevertheless, by effectively reducing disabilities related to cardiovascular events, statins have major benefits for public health. Therefore, clinicians should not withhold statin treatment awaiting proof of mortality benefits, as this may remain an 'untold story'.

Does Supplementation with Omega-3 PUFAs Add to the Prevention of Cardiovascular Disease?

PURPOSE OF REVIEW: Omega-3 fatty acids are increasingly used for the protection of cardiovascular disease. The main but not the sole mechanism of action is the reduction of triglyceride levels. In this review, we summarize the effect of omega-3 supplements on all-cause and cardiovascular mortality, myocardial infarction, and stroke from the relevant randomized controlled trials. RECENT FINDINGS: Twenty-one randomized controlled trials assessed omega-3 supplementation on mortality and cardiovascular-related outcomes. From these studies, as well as from the relevant meta-analyses, we found that omega-3 supplements do not exert a consistent benefit for cardiovascular protection. There is uncertainty of a clear profit from omega-3 supplementation in cardiovascular disease.

The current role of thiazolidinediones in diabetes management.

Among the epidemics of modern time, type 2 diabetes mellitus (T2DM) is one of the main contributors to overall morbidity as well as mortality. A number of different treatment options are available for the management of diabetes. Among them thiazolidinediones (TZDs) is an interesting drug class since it does not target the result of T2DM, i.e., hyperglycemia but rather some of the core mechanisms of the disease. Indeed, glitazones increase insulin sensitivity by activating the peroxisome proliferator-activated receptor γ, which plays an important role in regulating various metabolic parameters. Although TZDs have an established efficacy in T2DM treatment, their usage during the past years was questioned following the emergence of some alarming data regarding their safety and especially the cardiovascular safety of rosiglitazone. As a result, there is often some skepticism about the current role of TZDs in T2DM management. This mainly affects rosiglitazone even leading to its withdrawal from several markets in contrast to pioglitazone, which has shown a beneficial cardiovascular profile. A comprehensive assessment of the benefit-to-risk ratio of TZDs is required in order to better understand the place of these drugs in T2DM management.

NMR-based lipidomic analysis of blood lipoproteins differentiates the progression of coronary heart disease.

Abnormal lipid composition and metabolism of plasma lipoproteins play a crucial role in the pathogenesis of coronary heart disease (CHD). A (1)H NMR-based lipidomic approach was used to investigate the correlation of coronary artery stenosis with the atherogenic (non-HDL) and atheroprotective (HDL) lipid profiles in 99 patients with CHD of various stages of disease and compared with 60 patients with normal coronary arteries (NCA), all documented in coronary angiography. The pattern recognition models created from lipid profiles predicted the presence of CHD with a sensitivity of 87% and a specificity of 88% in the HDL model and with 90% and 89% in the non-HDL model, respectively. Patients with mild, moderate, and severe coronary artery stenosis were progressively differentiated from those with NCA in the non-HDL model with a statistically significant separation of severe stage from both mild and moderate. In the HDL model, the progressive differentiation of the disease stages was statistically significant only between patients with mild and severe coronary artery stenosis. The lipid constituents of lipoproteins that mainly characterized the initial stages and then the progression of the disease were the high levels of saturated fatty acids in lipids in both HDL and non-HDL particles, the low levels of HDL-phosphatidylcholine, HDL-sphingomyelin, and omega-3 fatty acids and linoleic acid in lipids in non-HDL particles. The conventional lipid marker, total cholesterol, found in low levels in HDL and in high levels in non-HDL, also contributed to the onset of the disease but with a much lower coefficient of significance. (1)H NMR-based lipidomic analysis of atherogenic and atheroprotective lipoproteins could contribute to the early evaluation of the onset of coronary artery disease and possibly to the establishment of an appropriate therapeutic option.

Emerging drugs for hyperlipidaemia: an update.

INTRODUCTION: Hypercholesterolaemia is a significant risk factor for cardiovascular disease (CVD), a major cause of morbidity and mortality. Up to now, the appropriate management has been aggressive hypolipidaemic therapy, particularly with statins, aiming at certain low-density lipoprotein cholesterol (LDL-C) levels for each patient population. This strategy has reduced CVD-related morbidity and mortality. However, many cardiovascular events still occur, probably as a consequence of lipid disorders other than high LDL-C concentration or other risk factors. Because statins do not eliminate the residual CVD risk, there seems to be place for novel lipid modifying drugs with different mechanisms of action. AREAS COVERED: This review is an update since 2010 regarding lipid-modifying drugs in development and their potent role in clinical practice. It focuses on cholesterol ester transfer protein inhibitors, mainly anacetrapib and evacetrapib, microsomal triglyceride transfer protein inhibitors, antisense oligonucleotides, pre-protein convertase subtilisin kexin-9 inhibitors and high-density lipoprotein mimetics. EXPERT OPINION: Several novel lipid-modifying drugs may be beneficial for certain patient populations. However, ongoing and future studies with clinical outcomes will clarify their actual role in clinical practice.

Fenofibrate and the kidney: an overview.

BACKGROUND: Fenofibrate has been used for the management of atherogenic dyslipidaemia for many years. Reports of fenofibrate-associated increases in serum creatinine (SCr) levels raised concerns regarding deleterious effects on renal function. DESIGN: In this narrative review, we discuss available literature on the effect of fenofibrate on the kidney. RESULTS: Most clinical studies showed a rapid (within weeks) raising effect of fenofibrate on SCr levels. This was often accompanied by declined estimated glomerular filtration rate. Risk predictors of this adverse effect might include increased age, impaired renal function and high-dose treatment. Also, the concomitant use of medications affecting renal hemodynamics (e.g. angiotensin-converting enzyme-inhibitors (ACEi) and angiotensin receptor blockers) may predispose to fenofibrate-associated increased SCr levels. Interestingly, SCr increases by fenofibrate were transient and reversible even without treatment discontinuation. Furthermore, fenofibrate was associated with a slower progression of renal function impairment and albuminuria in a long-term basis. Also, fenofibrate might be protective against pathological changes in diabetic nephropathy and hypertensive glomerulosclerosis. In this context, it is uncertain whether fenofibrate-associated increase in SCr levels mirrors true renal function deterioration. Several theories have been expressed. The most dominant one involved the inhibition of renal vasodilatory prostaglandins reducing renal plasma flow and glomerular pressure. Increased creatinine secretion or reduced creatinine clearance by fenofibrate was also suggested. These hypotheses should be settled by further studies. CONCLUSIONS: Fenofibrate may not be a nephrotoxic drug. However, a close monitoring of SCr levels is relevant especially in high-risk patients. Increases in SCr levels ≥30% can impose treatment discontinuation.

High-dose intravenous immunoglobulin in the treatment of adult patients with bullous pemphigoid.

High-dose intravenous immunoglobulin (IVIg) has only been sporadically used in the treatment of bullous pemphigoid (BP), as it is suggested as an adjuvant to systemic corticosteroids in progressive disease or when life-threatening complications are of concern with other therapeutic interventions. The aim of the present study was to report our observations in the treatment of adult BP patients with IVIg, in association with a focused literature review. In our Department we identified five patients (4 women, 1 man) who had received IVIg for BP relatively early in the course of their disease. These cases were added to the 36 adequately documented ones reported in the literature. Most of these patients (33/41) responded to treatment with IVIg and 7/33 responders remained clear one year after the onset of IVIg. However, the time for effective disease control after IVIg treatment depended positively on disease duration before treatment (P<0.01). In conclusion, despite the limited experience with its use, IVIg seems to be a useful therapeutic alternative to conventional modalities for selected BP patients, particularly if it is initiated promptly after BP diagnosis.

Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis.

CONTEXT: Considerable controversy exists regarding the association of omega-3 polyunsaturated fatty acids (PUFAs) and major cardiovascular end points. OBJECTIVE: To assess the role of omega-3 supplementation on major cardiovascular outcomes. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through August 2012. STUDY SELECTION: Randomized clinical trials evaluating the effect of omega-3 on all-cause mortality, cardiac death, sudden death, myocardial infarction, and stroke. DATA EXTRACTION: Descriptive and quantitative information was extracted; absolute and relative risk (RR) estimates were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic and I2. Subgroup analyses were performed for the presence of blinding, the prevention settings, and patients with implantable cardioverter-defibrillators, and meta-regression analyses were performed for the omega-3 dose. A statistical significance threshold of .0063 was assumed after adjustment for multiple comparisons. DATA SYNTHESIS: Of the 3635 citations retrieved, 20 studies of 68,680 patients were included, reporting 7044 deaths, 3993 cardiac deaths, 1150 sudden deaths, 1837 myocardial infarctions, and 1490 strokes. No statistically significant association was observed with all-cause mortality (RR, 0.96; 95% CI, 0.91 to 1.02; risk reduction [RD] -0.004, 95% CI, -0.01 to 0.02), cardiac death (RR, 0.91; 95% CI, 0.85 to 0.98; RD, -0.01; 95% CI, -0.02 to 0.00), sudden death (RR, 0.87; 95% CI, 0.75 to 1.01; RD, -0.003; 95% CI, -0.012 to 0.006), myocardial infarction (RR, 0.89; 95% CI, 0.76 to 1.04; RD, -0.002; 95% CI, -0.007 to 0.002), and stroke (RR, 1.05; 95% CI, 0.93 to 1.18; RD, 0.001; 95% CI, -0.002 to 0.004) when all supplement studies were considered. CONCLUSION: Overall, omega-3 PUFA supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association.

The role of statins in chronic kidney disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality not only amongst the general population, but also in patients with chronic kidney disease (CKD). Persons with CKD are much more likely to die of CVD than to experience kidney failure. Clinical trials have demonstrated that statins are gaining widespread acceptance as a principal therapy for the primary and secondary prevention of atherosclerosis and CVD. In CKD patients the role of statins in primary prevention of CVD remains to be clarified. The absolute benefit of treatment with a statin seems to be greater among nondialysis-dependent-CKD patients. Studies in end-stage renal disease patients on dialysis did not confirm these results. Recently, however, the Study of Heart and Renal Protection (SHARP) has suggested that statins with ezetimibe may be beneficial even in dialysis patients. Clinical studies with statins on proteinuria reduction and renal disease progression have yielded conflicting results. Some studies have shown a prominent reduction in proteinuria, while other studies have shown that statins had no effect or may cause proteinuria at high doses. This review examines the clinical evidence of the observed benefits of kidney function with the use of this drug category in CKD patients.

Emerging options in the treatment of dyslipidemias: a bright future?

INTRODUCTION: Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Low-density lipoprotein cholesterol (LDL-C) reduction has been demonstrated to decrease CVD-related morbidity and mortality. However, several patients do not reach LDL-C target levels with the currently available lipid lowering agents, particularly statins. Lipid and non-lipid parameters other than LDL-C may account for the residual CVD risk after adequate LDL-C lowering with statins. AREAS COVERED: This review focuses on the efficacy and safety of emerging drugs aiming at high-density lipoprotein cholesterol (HDL-C) elevation (i.e., recombinant or plasma-derived wild-type apolipoprotein (apo) A-I, apo A-I mimetic peptides, reconstituted mutant HDL, partially delipidated HDL and cholesterol ester transfer protein inhibitors), microsomal triglyceride transfer protein inhibitors and antisense oligonucleotides. EXPERT OPINION: Several lipid modifying agents in development may potently reduce the residual CVD risk. Ongoing and future studies with clinical outcomes will clarify their efficacy in clinical practice.

Evaluation of established coronary heart disease on the basis of HDL and non-HDL NMR lipid profiling.

A (1)H NMR-based lipid profiling approach was used to investigate the prediction of coronary heart disease (CHD) and examine the confounding effect of factors such as gender, triglycerides, HDL-cholesterol and age levels on the prediction of disease. The HDL and non-HDL lipid profiles in 47 patients with triple vessel disease (TVD) and 41 patients with normal coronary arteries (NCA) both documented angiographically were generated. The presence of CHD was predicted with a sensitivity and specificity of 52% and 75% for HDL model and 78% and 80% for non-HDL, respectively. The lipid constituents of HDL lipoproteins which contributed to the separation between the two groups were the saturated fatty acids, cholesterol, total omega-3 fatty acids, degree of unsaturation, diallylic protons from polyunsaturated fatty acids, linoleic acid and, to a lesser extent, the number of fatty acids, triglycerides, unsaturated fatty acids and phosphatidylcholine. Respectively, for non-HDL, lipoproteins were the saturated fatty acids, number of fatty acids, cholesterol, unsaturated fatty acids and phosphatidylcholine. Gender, triglycerides, HDL-cholesterol and age influenced the lipid constituents of HDL and non-HDL lipoproteins that contributed to the separation between subgroups and confounded the predictive power of the models. NMR-based lipid profiling analysis could contribute to the identification of noninvasive markers for the presence and the development of the disease.

Rosuvastatin-associated adverse effects and drug-drug interactions in the clinical setting of dyslipidemia.

HMG-CoA reductase inhibitors (statins) are the mainstay in the pharmacologic management of dyslipidemia. Since they are widely prescribed, their safety remains an issue of concern. Rosuvastatin has been proven to be efficacious in improving serum lipid profiles. Recently published data from the JUPITER study confirmed the efficacy of this statin in primary prevention for older patients with multiple risk factors and evidence of inflammation. Rosuvastatin exhibits high hydrophilicity and hepatoselectivity, as well as low systemic bioavailability, while undergoing minimal metabolism via the cytochrome P450 system. Therefore, rosuvastatin has an interesting pharmacokinetic profile that is different from that of other statins. However, it remains to be established whether this may translate into a better safety profile and fewer drug-drug interactions for this statin compared with others. Herein, we review evidence with regard to the safety of this statin as well as its interactions with agents commonly prescribed in the clinical setting. As with other statins, rosuvastatin treatment is associated with relatively low rates of severe myopathy, rhabdomyolysis, and renal failure. Asymptomatic liver enzyme elevations occur with rosuvastatin at a similarly low incidence as with other statins. Rosuvastatin treatment has also been associated with adverse effects related to the gastrointestinal tract and central nervous system, which are also commonly observed with many other drugs. Proteinuria induced by rosuvastatin is likely to be associated with a statin-provoked inhibition of low-molecular-weight protein reabsorption by the renal tubules. Higher doses of rosuvastatin have been associated with cases of renal failure. Also, the co-administration of rosuvastatin with drugs that increase rosuvastatin blood levels may be deleterious for the kidney. Furthermore, rhabdomyolysis, considered a class effect of statins, is known to involve renal damage. Concerns have been raised by findings from the JUPITER study suggesting that rosuvastatin may slightly increase the incidence of physician-reported diabetes mellitus, as well as the levels of glycated hemoglobin in older patients with multiple risk factors and low-grade inflammation. Clinical trials proposed no increase in the incidence of neoplasias with rosuvastatin treatment compared with placebo. Drugs that antagonize organic anion transporter protein 1B1-mediated hepatic uptake of rosuvastatin are more likely to interact with this statin. Clinicians should be cautious when rosuvastatin is co-administered with vitamin K antagonists, cyclosporine (ciclosporin), gemfibrozil, and antiretroviral agents since a potential pharmacokinetic interaction with those drugs may increase the risk of toxicity. On the other hand, rosuvastatin combination treatment with fenofibrate, ezetimibe, omega-3-fatty acids, antifungal azoles, rifampin (rifampicin), or clopidogrel seems to be safe, as there is no evidence to support any pharmacokinetic or pharmacodynamic interaction of rosuvastatin with any of these drugs. Rosuvastatin therefore appears to be relatively safe and well tolerated, sharing the adverse effects that are considered class effects of statins. Practitioners of all medical practices should be alert when rosuvastatin is prescribed concomitantly with agents that may increase the risk of rosuvastatin-associated toxicity.

Apolipoprotein B-to-A1 ratio as a predictor of acute ischemic nonembolic stroke in elderly subjects.

Among traditional cardiovascular risk factors, apolipoprotein (apo)B/apoA1 ratio is considered to have the strongest predictive value for ischemic stroke. Nevertheless, there are imsufficient data to support this ratio as an independent risk predictor of ischemic stroke in elderly individuals. In this case-control study, we evaluated apoB/apoA1 ratio as a predictor of ischemic stroke in a cohort of elderly subjects. A total of 163 patients aged>70 years (88 men) admitted due to a first-ever acute ischemic/nonembolic stroke and 166 volunteers (87 men) with no history of cardiovascular disease were included. The association between apoB/apoA1 ratio and stroke was determined by multivariate logistic regression modeling after adjusting for potential confounding factors, including lipid parameters. Stroke patients exhibited a higher apoB/apoA1 ratio than controls (1.04±0.33 vs 0.86±0.22; P<.001). In univariate analysis, crude odds ratio (OR) for apoB/apoA1 ratio was 1.27 per 0.1 increase (95% confidence interval [CI]=1.15-1.39; P<.001). Compared with subjects with an apoB/apoA1 ratio in the lowest quartile, those within the highest quartile had a 6.3-fold increase in the odds of suffering an ischemic stroke (95% CI=3.17-12.48; P<.001). This association remained significant after controlling for potential confounders, including sex, age, smoking status, body mass index, waist circumference, glucose and insulin levels, the presence of hypertension and diabetes mellitus, and lipid profile parameters (adjusted OR=3.02; 95% CI=1.16-7.83; P=.02). Our findings support elevated apoB/apoA1 ratio as an independent predictor of ischemic stroke in individuals over age 70.

Cardioprotective Properties of HDL: Structural and Functional Considerations.

BACKGROUND: As Mendelian Randomization (MR) studies showed no effect of variants altering HDL-cholesterol (HDL-C) levels concerning Cardiovascular Disease (CVD) and novel therapeutic interventions aiming to raise HDL-C resulted to futility, the usefulness of HDL-C is unclear. OBJECTIVE: As the role of HDL-C is currently doubtful, it is suggested that the atheroprotective functions of HDLs can be attributed to the number of HDL particles, and their characteristics including their lipid and protein components. Scientific interest has focused on HDL function and on the causes of rendering HDL particles dysfunctional, whereas the relevance of HDL subclasses with CVD remains controversial. METHODS: The present review discusses changes in quality as much as in quantity of HDL in pathological conditions and the connection between HDL particle concentration and cardiovascular disease and mortality. Emphasis is given to the recently available data concerning the cholesterol efflux capacity and the parameters that determine HDL functionality, as well as to recent investigations concerning the associations of HDL subclasses with cardiovascular mortality. RESULTS: MR studies or pharmacological interventions targeting HDL-C are not in favor of the hypothesis of HDL-C levels and the relationship with CVD. The search of biomarkers that relate with HDL functionality is needed. Similarly, HDL particle size and number exhibit controversial data in the context of CVD and further studies are needed. CONCLUSION: There is no room for the old concept of HDL as a silver bullet,as HDL-C cannot be considered a robust marker and does not reflect the importance of HDL particle size and number. Elucidation of the complex HDL system, as well as the finding of biomarkers, will allow the development of any HDL-targeted therapy.

Arterial Stiffness, Cognitive Dysfunction and Adherence to Antihypertensive Agents. Is there a Link to Hypertensive Patients?

The incidence of hypertension (HTN) and its cardiovascular (CV) complications are increasing throughout the world. Blood pressure (BP) control remains unsatisfactory worldwide. Medical inertia and poor adherence to treatment are among the factors that can partially explain, why BP control rate remains low. The introduction of a method for measuring the degree of adherence to a given medication is now a prerequisite. Complex treatment regimes, inadequate tolerance and frequent replacements of pharmaceutical formulations are the most common causes of poor adherence. In contrast, the use of stable combinations of antihypertensive drugs leads to improved patient adherence. We aim to review the relationships between arterial stiffness, cognitive function and adherence to medication in patients with HTN. Large artery stiffening can lead to HTN. In turn, arterial stiffness induced by HTN is associated with an increased CV and stroke risk. In addition, HTN can induce disorders of brain microcirculation resulting in cognitive dysfunction. Interestingly, memory cognitive dysfunction leads to a reduced adherence to drug treatment. Compliance with antihypertensive treatment improves BP control and arterial stiffness indices. Early treatment of arterial stiffness is strongly recommended for enhanced cognitive function and increased adherence.