The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials.

AIMS: The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events. METHODS AND RESULTS: We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84-0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85-0.99) but not HF death (213/57 734 vs. 220/57 836; RR 0.97, 95% CI 0.80-1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68-1.11) or not (RR 0.91, 95% CI 0.84-0.98). CONCLUSION: In primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not.

Should we expand the concept of coronary heart disease equivalents?

PURPOSE OF REVIEW: This narrative review discusses the associations between metabolic and inflammatory diseases, as well as radiotherapy and chemotherapy with coronary heart disease (CHD) and related risk factors, to support (or not) their potential role as CHD equivalents. RECENT FINDINGS: Although not regarded as CHD equivalents, several metabolic and inflammatory disorders are associated with an increased risk of CHD morbidity and/or mortality. These conditions include metabolic syndrome, impaired glucose metabolism, nonalcoholic fatty liver disease, obstructive sleep apnoea syndrome, erectile dysfunction, periodontitis, inflammatory bowel diseases, systemic vasculitis and HIV infection, as well as chemotherapy and radiotherapy. SUMMARY: More research should be carried out to identify which conditions can be added to the list of CHD equivalents.

Serum adipokine levels in patients with type 1 diabetes are associated with degree of obesity but only resistin is independently associated with atherosclerosis markers.

PURPOSE: The role of adipokines in causing inflammation and insulin resistance in normal weight and obese patients is generally well studied. However, there are often conflicting results regarding their levels in type 1 diabetes mellitus (T1DM) patients and their relationship to micro- and macrovascular disease. We therefore investigated which serum adipokine levels are independently associated with markers of early atherosclerosis and microvascular complications in patients with T1DM. METHODS: A cross-sectional study was performed in the Diabetes Outpatient Clinic of Hippokrateion General Hospital, Thessaloniki, Greece. Sixty T1DM patients (30 females, mean age 38.8 ± 10.6 years, mean diabetes duration 17.4 ± 9.9 years) were included. Plasma adiponectin, leptin, and resistin, carotid artery intima media thickness (cIMT), and arterial stiffness (pulse wave velocity, PWV/SpygmoCor CP System and Mobil-O-Graph 24 h PWA) were assessed. RESULTS: Leptin and resistin levels were significantly higher in overweight and obese patients (p = 0.002 and p = 0.039, respectively). Adiponectin was the only adipokine negatively correlated with BMI (rs = - 0.41, p = 0.001). We report a bivariate association between serum adiponectin levels and retinopathy (p = 0.007). Resistin was the only adipokine that showed significant correlation with systolic (rs = 0.42, p = 0.001) and diastolic (rs = 0.29, p = 0.024) hypertension and PWV (p = 0.035). CONCLUSIONS: Serum adipokine levels demonstrate similar bivariate associations with anthropometric variables in patients with T1DM to those in normal weight subjects. Although microvascular complications are associated with serum adipokine levels by bivariate analysis, only resistin, an inflammatory marker, is independently associated with arterial stiffness in patients with T1DM.

Right ventricular performance in patients with heart failure with mildly reduced ejection fraction: the forgotten ventricle.

Right ventricular (RV) function is a major determinant of prognosis and adverse outcomes in patients with heart failure (HF). It is largely unknown if HF with mildly reduced ejection fraction (HFmrEF) patients have some special characteristics in RV function (RVF) that may distinguish them from HF with reduced or preserved ejection fraction (HFrEF or HFpEF) patients. Standard echocardiography was performed to estimate RVF [tricuspid annular systolic velocity (TDSV), plane systolic excursion (TAPSE), TAPSE to pulmonary artery systolic pressure (TAPSE/PASP) and RV myocardial performance index (MPI-TEI index)] in a cross-sectional study. In 306 participants, the RV systolic function evaluated with TAPSE and TDSV was impaired in 39.1 and 24.2%, respectively. TAPSE, TAPSE/PASP and TDSV were lower in HFmrEF compared with HFpEF and higher compared with HFrEF (p < 0.001 for among-groups comparison). RV diastolic dysfunction varied between 12.6 and 43.8% depending on the echocardiographic parameter. Diastolic RVF determined by tricuspid inflow E/A wave ratio (Et/At) was impaired in less patients with HFmrEF compared with those with HFpEF or HFrEF (25.9% vs 48.4% vs 56.3%; p = 0.030, respectively). RV diastolic dysfunction by et'/at' (tissue Doppler tricuspid valve annulus e' and a' waves) was impaired in less patients with HFmrEF compared with HFrEF (11.8% vs 33.3%; p = 0.019). A multivariate regression analysis revealed a significant association between RV and LV systolic dysfunction. The present study shows a high prevalence of RV dysfunction in HFmrEF patients. Study findings provides some new insights on RV and LV systolic dysfunction coupling whereas RV diastolic dysfunction was not dependent on LV systolic dysfunction.

Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis.

BACKGROUND: Long-term statin treatment reduces the frequency of cardiovascular events, but safety and efficacy in patients with abnormal liver tests is unclear. We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study population. METHODS: GREACE was a prospective, intention-to-treat study that randomly assigned by a computer-generated randomisation list 1600 patients with coronary heart disease (aged <75 years, with serum concentrations of LDL cholesterol >2·6 mmol/L and triglycerides <4·5 mmol/L) at the Hippokration University Hospital, Thessaloniki, Greece to receive statin or usual care, which could include statins. The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests (defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal) compared with patients with abnormal liver tests who did not receive a statin. This risk reduction was compared with that for patients treated (or not) with statin and normal liver tests. FINDINGS: Of 437 patients with moderately abnormal liver tests at baseline, which were possibly associated with non-alcoholic fatty liver disease, 227 who were treated with a statin (mainly atorvastatin 24 mg per day) had substantial improvement in liver tests (p<0·0001) whereas 210 not treated with a statin had further increases of liver enzyme concentrations. Cardiovascular events occurred in 22 (10%) of 227 patients with abnormal liver tests who received statin (3·2 events per 100 patient-years) and 63 (30%) of 210 patients with abnormal liver tests who did not receive statin (10·0 events per 100 patient-years; 68% relative risk reduction, p<0·0001). This cardiovascular disease benefit was greater (p=0·0074) than it was in patients with normal liver tests (90 [14%] events in 653 patients receiving a statin [4·6 per 100 patient-years] vs 117 [23%] in 510 patients not receiving a statin [7·6 per 100 patient-years]; 39% relative risk reduction, p<0·0001). Seven (<1%) of 880 participants who received a statin discontinued statin treatment because of liver-related adverse effects (transaminase concentrations more than three-times the upper limit of normal). INTERPRETATION: Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease. FUNDING: None.

Ertugliflozin + metformin as a treatment option for type 2 diabetes.

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce blood glucose and glycosylated hemoglobin (HbA1c), the risk of hospitalization for heart failure (HF) and the incidence of serious adverse kidney function events (chronic kidney disease, CKD) in patients with type 2 diabetes mellitus (T2DM). Ertugliflozin is the last SGLT2i approved by Food and Drug Administration (FDA) in the USA and European Medical Agency (EMA) in Europe for the treatment of T2DM alone or in combination with other drugs.Areas covered: The authors critically discuss in this drug evaluation the safety and efficacy of the ertugliflozin + metformin combination in patients with T2DM without complications, those with CKD, or those with heart failure (HF). Furthermore, the authors discuss the results of the VERTIS CV trial (MK-8835-004), the trials NCT01986881 and NCT01986855 and other smaller studies.Expert opinion: The ertugliflozin + metformin combination is safe and effective in patients with T2DM with renal impairment, HF of any kind, or those without diabetic complications. These have practical implications that will help diabetologists, cardiologists, internists, nephrologists and general practitioners in selecting the proper combination of SGLT2i on top of metformin, if needed.

Rosuvastatin and ezetimibe for the treatment of dyslipidemia and hypercholesterolemia.

Introduction: Statins are powerful lipid-lowering agents which reduce cardiovascular (CV)-related morbidity and mortality. However, a large proportion of patients cannot attain the target low-density lipoprotein cholesterol (LDL-C) levels, despite receiving maximally tolerated doses of high-intensity statins. Also, adherence to treatment may be reduced due to statin-induced myopathy or other side effects. For these reasons, guidelines recommend adding the cholesterol absorption inhibitor ezetimibe.Areas covered: Authors discuss the main pharmacological characteristics of rosuvastatin and ezetimibe, their lipid-lowering and pleiotropic effects, as well as the clinical effects of the fixed dose combination of these drugs when used to treat dyslipidemia.Expert opinion: The rosuvastatin/ezetimibe combination is safe and effective in patients with hypercholesterolemia or dyslipidemia with or without diabetes and with or without cardiovascular disease. This drug combination enabled higher proportions of patients to achieve recommended LDL-C goals than rosuvastatin monotherapy or the simvastatin/ezetimibe combination, without additional adverse events. Despite the lack of additional CV outcomes data and comparisons with atorvastatin/ezetimibe, rosuvastatin/ezetimibe appears as a potent and generally well-tolerated drug combination eligible for the management of hypercholesterolemia and dyslipidemia in adults. Recently, the 40 mg rosuvastatin/10 mg ezetimibe fixed combination was approved and is also evaluated.

Prevalence, Diagnosis, and Treatment with 3 Different Statins of Non-alcoholic Fatty Liver Disease/Non-alcoholic Steatohepatitis in Military Personnel. Do Genetics Play a Role?

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), are major health problems worldwide. Genetics may play a role in the pathogenesis of NAFLD/NASH. AIMS: To investigate the prevalence of NAFLD/NASH in 5,400 military personnel and evaluate the effect of treatment with 3 statins on NAFLD/NASH using 2 non-invasive scores [NAFLD Activity Score (NAS); Fibrosis-4 score (FIB-4)]. METHODS: During the mandatory annual medical check-up, military personnel underwent a clinical and laboratory evaluation. Participants with NAFLD/NASH were randomized into 4 groups (n=151 each): diet-exercise, atorvastatin, rosuvastatin, or pitavastatin for 1 year (i.e., until the next routine evaluation). RESULTS: From all the participants, 613 had NAFLD/NASH (prevalence 11.3 vs 39.8% in the general population, p<0.001), and a total of 604 consented to participate in the study. After a year of treatment, the diet-exercise group showed no significant changes in both scores (NAS 4.98 baseline vs. 5.62, p=0.07; FIB-4 3.42 vs. 3.52, p=0.7). For the atorvastatin group, both scores were reduced (NAS 4.97 vs 1.95, p<0.001, FIB-4 3.56 vs 0.83, p<0.001), for rosuvastatin (NAS 5.55 vs 1.81, p<0.001, FIB-4 3.61 vs 0.79, p<0.001), and for pitavastatin (NAS 4.89 vs 1.99, p<0.001, FIB-4 3.78 vs 0.87, p<0.001). CONCLUSION: Atorvastatin, rosuvastatin, and pitavastatin have a beneficial and safe effect in NAFLD/NASH patients as recorded by the improvement in the NAS (representing NAFLD activity) and FIB-4 (representing liver fibrosis) scores. Since both those with and without NAFLD/- NASH shared several baseline characteristics, genetics may play a role in the pathogenesis of NAFLD/NASH and its treatment with statins.

The role of ankle brachial index and carotid intima-media thickness in vascular risk stratification.

PURPOSE OF REVIEW: To summarize recent findings on the role of ankle brachial index (ABI) and carotid intima-media thickness (cIMT) in vascular risk stratification. RECENT FINDINGS: The combination of either ABI or cIMT with the Framingham risk score does not appear to improve risk stratification more than the Framingham risk score alone. SUMMARY: ABI and cIMT are well studied markers of atherosclerotic burden. Considerable evidence shows that they both are independently associated with increased vascular morbidity and mortality. However, their value in identifying high-risk patients among those with low or intermediate estimated risk appears to be limited. Regarding cIMT, this might be because cIMT is mostly a marker of early atherosclerosis. On the contrary, peripheral arterial disease (i.e. ABI <0.9) develops mostly in patients who already have high estimated vascular risk (e.g. elderly smokers or diabetic patients). Nevertheless, ABI is inexpensive, can be performed quickly and has high validity and good reproducibility, in contrast to the technical equipment and expertise required for measuring cIMT. Accordingly, ABI should be measured in patients at risk for peripheral arterial disease but not in all intermediate-risk patients indiscriminately. Finally, it has not been evaluated whether adding ABI or cIMT to the Framingham risk equation to guide management decisions will prevent more events than the use of the Framingham risk equation alone. Before the wider implementation of ABI or cIMT for risk stratification, this critical question has to be answered.

Aggressive statin treatment, very low serum cholesterol levels and haemorrhagic stroke: is there an association?

PURPOSE OF REVIEW: To assess the potential association between haemorrhagic stroke and achieving very low serum cholesterol levels with aggressive statin treatment. RECENT FINDINGS: The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study showed a reduction in both fatal and nonfatal stroke but an increase in the risk for haemorrhagic stroke during high-dose atorvastatin treatment. However, post-hoc analyses of this trial showed that this increased risk is primarily observed in elderly men with a history of haemorrhagic stroke. In addition, there was no relationship between baseline or on-treatment low-density lipoprotein cholesterol (LDL-C) levels and haemorrhagic stroke. SUMMARY: Existing data suggest that low LDL-C levels during intensive statin treatment are not associated with an increased risk for haemorrhagic stroke, except in patients with a history of intracerebral haemorrhage. In patients with a history of ischaemic stroke, intensive statin treatment substantially reduces the risk for both recurrent ischaemic stroke and for coronary heart disease (CHD) events. Any possible excess of haemorrhagic stroke is greatly outweighed by the protective effect against ischaemic stroke and CHD events.

Dysmetabolic Iron Overload in Metabolic Syndrome.

BACKGROUND: We sought to determine the association of dysmetabolic iron overload syndrome (DIOS) with metabolic syndrome (MetS). METHODS: Several studies have shown that DIOS is associated with Mets, mainly through the pathogenesis of its components: type 2 diabetes mellitus (T2DM), essential hypertension, non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (POS). RESULTS: Serum ferritin levels increase proportionally according to the degree of insulin resistance (IR) and the number of components of Mets. Moreover, DIOS predicts the onset of T2DM and NAFLD. Dysregulation of iron metabolism in DIOS is due to a multifactorial and dynamic process triggered by an unhealthy diet, facilitated by environmental and genetic cofactors, and resulting in a bidirectional relation between the liver and visceral adipose tissue (VAT). Iron removal combined with a healthy diet improved both insulin sensitivity and beta-cell function, but had no significant effect on blood glucose; however, phlebotomy therapy might be considered with conflicting results. CONCLUSION: Iron overload is closely associated with metabolic syndrome and its components; however, it remains under-appreciated in everyday clinical practice. Diet and lifestyle modification offer some clinical benefit; however, it is not adequate for successful management of the disease. The results of phlebotomy remain controversial, underlying the necessity of further efforts in this field.

Treatment strategies for hypertension in patients with type 1 diabetes.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is a chronic, autoimmune disease that is characterized by total absence of insulin production. Hypertension is a common comorbidity in T1DM with complex pathophysiology, while it is also a well-recognized risk factor for the development of cardiovascular disease (CVD), as well as other microvascular diabetic complications. AREAS COVERED: The purpose of this review is to present the current definitions, epidemiological data and prevalence rates of hypertension in T1DM, as well as to describe current therapeutic options. EXPERT OPINION: Hypertension affects around a third of the type 1 diabetic population, with higher prevalence rates in older individuals with longer disease duration. Although hypertension affects a substantial proportion of T1DM individuals, blood pressure control rates are disappointingly low. Alongside lifestyle modification, antihypertensive treatment should be initiated in those with blood pressure above 140/90 mmHg, with a systolic blood pressure target of 130 mmHg and lower, if tolerated. In those with established CVD or diabetic nephropathy, systolic blood pressure targets below 130 mmHg should be pursued. Initial pharmacotherapy should consist of a renin-angiotensin-aldosterone system inhibitor. There is an urgent need for good quality data regarding proper antihypertensive treatment initiation, optimal BP targets and optimal antihypertensive treatment for better clinical outcomes.

Efficacy and safety of statin use in children and adolescents with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized-controlled trials.

PURPOSE: Statins are the mainstay of treatment for patients with familial hypercholesterolaemia (FH). However, their efficacy and safety in children and adolescents with FH has not been well-documented. The purpose of this study was to systematically investigate and meta-analyze the best available evidence from randomized-controlled trials (RCTs) regarding the efficacy and safety of statins in this population. METHODS: A comprehensive search was conducted in PubMed, Scopus and Cochrane, up to 10 January 2020. Data were expressed as mean differences with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. RESULTS: Ten RCTs were included in the qualitative and quantitative analysis (1191 patients, aged 13.3 ± 2.5 years). Compared with placebo, statins led to a mean relative reduction in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride and apolipoprotein B (apo-B) concentrations by -25.5% (95% CI -30.4%, -20.5%; I2 91%), -33.8% (95% CI -40.1%, -27.4%; I2 90%), -8.4% (95% CI -14.8%, -2.03%; I2 26%) and -28.8% (95% CI -33.9%, -23.6%; I2 83%), respectively. High-density lipoprotein cholesterol (HDL-C) was increased by 3.1% (95% CI 1.1%-5.2%; I2 0%). Statins were well-tolerated, with no significant differences in transaminase and creatine kinase levels or other adverse effects compared with placebo. Statins exerted no effect on growth or sexual development. CONCLUSION: Statins are quite effective in reducing TC, LDL-C, TG and apo-B and increasing HDL-C concentrations in children and adolescents with FH. No safety issues were seen with statin use.

Non-Alcoholic Fatty Liver Disease Treatment in Patients with Type 2 Diabetes Mellitus; New Kids on the Block.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), affecting over 25% of the general population worldwide, is characterized by a spectrum of clinical and histological manifestations ranging from simple steatosis (>5% hepatic fat accumulation without inflammation) to non-alcoholic steatohepatitis (NASH) which is characterized by inflammation, and finally fibrosis, often leading to liver cirrhosis, and hepatocellular carcinoma. Up to 70% of patients with type 2 diabetes mellitus (T2DM) have NAFLD, and diabetics have much higher rates of NASH compared with the general non-diabetic population. OBJECTIVE: The aim of this study is to report recent approaches to NAFLD/NASH treatment in T2DM patients. To-date, there are no approved treatments for NAFLD (apart from lifestyle measures). RESULTS: Current guidelines (2016) from 3 major scientific organizations suggest that pioglitazone and vitamin E may be useful in a subset of patients for adult NAFLD/NASH patients with T2DM. Newer selective PPAR-γ modulators (SPPARMs, CHRS 131) have shown to provide even better results with fewer side effects in both animal and human studies in T2DM. Newer antidiabetic drugs might also be useful, but detailed studies with histological outcomes are largely lacking. Nevertheless, prior animal and human studies on incretin mimetics, glucagon-like peptide-1 receptor agonists (GLP-1 RA) approved for T2DM treatment, have provided indirect evidence that they may also ameliorate NAFLD/NASH, whereas dipeptidyl dipeptidase-4 inhibitors (DDP-4i) were not better than placebo in reducing liver fat in T2DM patients with NAFLD. Sodium-glucoseco-transporter-2 inhibitors (SGLT2i) have been reported to improve NAFLD/NASH. Statins, being necessary for most patients with T2DM, may also ameliorate NAFLD/NASH, and could potentially reinforce the beneficial effects of the newer antidiabetic drugs, if used in combination, but this remains to be identified. CONCLUSION: Newer antidiabetic drugs (SPPARMs, GLP-1 RA and SGLT2i) alone or in combination and acting alone or with potent statin therapy which is recommended in T2DM, might contribute substantially to NAFLD/NASH amelioration, possibly reducing not only liver-specific but also cardiovascular morbidity. These observations warrant long term placebo-controlled randomized trials with appropriate power and outcomes, focusing on the general population and more specifically on T2DM with NAFLD/NASH. Certain statins may be useful for treating NAFLD/NASH, while they substantially reduce cardiovascular disease risk.

Anti-inflammatory effects of fibrates: an overview.

Inflammation plays an important role in the pathogenesis of atherosclerosis. Several cardiovascular drugs exert anti-inflammatory effects and accumulating data suggest that fibrates also share this property. This review summarizes the mechanisms implicated in the anti-inflammatory actions of fibrates. We also provide an overview of the existing clinical studies addressing the effects of fibrates on markers of inflammation. Several, but not all, studies reported that fibrates exert anti-inflammatory actions. The small number of patients included in some studies, as well as differences in diagnoses and duration of follow up might partly explain this discrepancy. It is also possible that fibrates differ substantially in terms of anti-inflammatory effects. It is not clear whether an anti-inflammatory action of fibrates is clinically relevant. Future studies should assess whether the anti-inflammatory actions of fibrates (or for that matter, other drugs) will translate into a reduced risk of vascular disease.

Statins and cardiovascular events in patients with end-stage renal disease on hemodialysis. The AURORA results suggest the need for earlier intervention.

The recently published Assessment of Survival and Cardiovascular Events (AURORA) trial showed that rosuvastatin (10 mg/d) compared with placebo did not result in a significant reduction in vascular events despite a 43% fall in low density lipoprotein cholesterol (LDL-C) levels in patients with end-stage renal disease (ESRD). The reasons for this and previous negative findings are discussed. In contrast, there is evidence that statins exert a nephroprotective action in less advanced chronic kidney disease (CKD). There is need for further trials to establish if patients at various stages of CKD will benefit from statin treatment in terms of both nephroprotection and reduction in vascular events.

Lipoprotein a: where are we now?

PURPOSE OF REVIEW: To provide an update of the literature describing the link between lipoprotein a and vascular disease. RECENT FINDINGS: There is evidence that elevated plasma lipoprotein a levels are associated with coronary heart disease, stroke and other manifestations of atherosclerosis. Several mechanisms may be implicated, including proinflammatory actions and impaired fibrinolysis. SUMMARY: Lipoprotein a potentially represents a useful tool for risk stratification in the primary and secondary prevention setting. However, there are still unresolved methodological issues regarding the measurement of lipoprotein a levels. Targeting lipoprotein a in order to reduce vascular risk is hampered by the lack of well tolerated and effective pharmacological interventions. Moreover, it has not yet been established whether such a reduction will result in fewer vascular events. The risk attributed to lipoprotein a may be reduced by aggressively tackling other vascular risk factors, such as low-density lipoprotein cholesterol.