Low-density Lipoprotein Cholesterol Treatment Research Articles

Real-life LDL-C treatment goals achievement in patients with heterozygous familial hypercholesterolemia in the Czech Republic and Slovakia: Results of the PLANET registry

Background and aimsDespite the high prevalence of familial hypercholesterolemia (FH) and available effective lipid-lowering therapy, most of the individuals with this disorder remain undiagnosed and undertreated. The aim of the PLANET registry was to assess the real-life attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic target level in patients with heterozygous FH, to characterize prescribed lipid-lowering therapy with assessment of its efficiency according to the attainment of the target LDL-C level, and to characterize cardiovascular events observed in this patient population again in relation to LDL-C target level attainment. MethodsPLANET registry was designed as a non-interventional, retrospective, cross-sectional, multicentre disease registry for adult patients with heterozygous FH in the Czech Republic and Slovakia. ResultsOverall, 1755 patients were enrolled at 32 sites specialized in FH treatment. 15.4% of patients attained the target LDL-C value. The proportion of patients with LDL-C goal achievement increased to 17.3% in the subgroup of patients receiving high-intensity statin therapy (54.6% of study population). Out of 55 patients receiving inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), 61.8% reached the LDL-C treatment goal. Of all cardiovascular events reported, 14.0% occurred in patients attaining the LDL-C goal, while it was 86.0% in the not-at-target group. It was documented (p=0.004) that the longer is the patient in care at the specialized FH centre, the higher is the probability that he/she will attain the target LDL-C level. ConclusionsAlthough target LDL-C level attainment remains relatively low, the likelihood of LDL-C goal attainment increases with duration of specialized care.

Non-HDL-C goals based on the distribution of population percentiles in ELSA-Brasil: Is it time to change?

Background and aimsNon–high-density lipoprotein cholesterol (non-HDL-C) goals are defined as 30 mg/dL (0.78 mmol/L) higher than the respective low-density lipoprotein cholesterol (LDL-C) goals. This definition, however, do not consider the population distribution of non-HDL-C, which could represent a more appropriate individual goal when both markers are discordant. The aim of this study is to establish non-HDL-C goals at the same population percentiles of LDL-C. MethodsNon-HDL-C values were assigned at the same percentiles correspondent to the LDL-C treatment goals for 14,837 participants from the Longitudinal Study of Adult Health (ELSA-Brasil) with triglycerides levels ≤ 400 mg/dL (4.52 mmol/L). We also assessed the frequency of reclassification, defined as the number of subjects with LDL-C levels in the recommended therapeutic category, but with non-HDL-C levels above or below the category. ResultsThe non-HDL-C values, based on correspondent LDL-C population percentiles, were 92 (2.38), 122 (3.16), 156 (4.04), 191 (4.95), and 223 mg/dL (5.78 mmol/L). Among participants with LDL-C <70 mg/dL (1.81 mmol/L), 22.8% were reclassified in a higher category according to the guidelines-based non-HDL-C cut-off and 30.1% according to the population percentile-based cut-off; 25.6% and 64.1%, respectively, if triglycerides concurrently 150–199 mg/dL (1.69–2.25 mmol/L). ConclusionsOur results demonstrated that non-HDL-C percentiles-based goals were up to 8 mg/dL (0.21 mmol/L) lower than the guidelines recommended goal and had a profound impact on the reclassification of participants, notably when LDL-C was <100 mg/dL (2.56 mmol/L), the treatment goal for high risk patients. Therefore, non-HDL-C goals should be changed for reduction of residual risk.

Lipid-lowering therapy with PCSK9-inhibitors in the management of cardiovascular high-risk patients: Effectiveness, therapy adherence and safety in a real world cohort.

Proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibitors have shown great po-tential in efficient lipid lowering to achieve low-density lipoprotein-cholesterol (LDL-C) treatment goals. The aim of the study was too describe the clinical use of PCSK9-inhibitors and to investigate therapy adherence and safety outside of clinical trials. Thirty-eight patients were treated with PSCK9-inhibitors. Patients were eligible for this therapy based on their individual cardiovascular risk and when all other available lipid-lowering regi-men had failed. Every patient answered a questionnaire concerning medical history and relevant side effects and therapy adherence. Conventional therapy reduced patient LDL-C levels by about 38%. However, in 26 of the 38 patients, LDL-C treatment goals were not fulfilled because patients did not tolerate further dose es-calation due to side effects. Using a PCSK9 inhibitor, LDL-C levels were reduced by another 54% and 42% of patients reaching treatment goals. The results show that most patients still require concomitant therapy to reach LDL-C target levels. Three patients required dose reduction or change of the PCSK9 inhibitor. 16% did not inject the PCSK9 inhibitor regularly. Only a minority of patients reached the recommended LDL-C goals. PCSK9-inhibitors were generally well tolerated. Despite low rates of reported side effects, therapy adherence was incom-plete, with 6 patients not injecting PCSK9-inhibitors on a regular basis. In-depth information about the medication and close supervision is advisable. PCSK9 inhibitors have shown great potential in aggressive lipid lowering therapy, but basic therapy is still required in most cases. Close supervision is recommended to improve therapy adherence. (Cardiol J 2018; 25, 1: 32-41).

Treatment Patterns and Lipid Profile in Patients with Familial Hypercholesterolemia in Japan.

Aim: To evaluate the epidemiology and real-world treatment patterns associated with lipid-modifying therapies (LMTs) among groups of Japanese patients with familial hypercholesterolemia (FH).Methods: A retrospective observational study was conducted using an electronic hospital-based administrative claims database and electronic medical records. Patients with existing diagnosis of FH (FH-D) and patients with suspected FH (FH-S) defined by low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL were included, and medical records of hospitals across Japan were analyzed to assess the diagnostic status, management of LDL-C levels, and treatment patterns.Results: Among the 3,495 patients who met the inclusion criteria, 193 patients were FH-D and 3,339 patients were FH-S. Among them, 83.5% had not achieved the LDL-C of < 100 mg/dL recommended for patients with FH at the index date. Mean LDL-C levels for all patients and for FH-D and FH-S patients were 145.8 mg/dL, 119.2 mg/dL, and 147.6 mg/dL, respectively. 44.5% of the patients were not currently treated with LMTs. High-intensity statins were used only in 19.2% and 2.3% of the FH-D and FH-S patients, respectively. Furthermore, among the FH-D and FH-S statin-treated patients, 61 (69.3%) and 1,059 (89.7%) remained on monotherapy even when their LDL-C was ≥ 100 mg/dL.Conclusions: Treatment and management of LDL-C in Japanese FH patients remain suboptimal. The results suggest that FH is underdiagnosed in real-world, routine clinical practice in Japan. There is an urgent need to improve the diagnostic rate of FH and to provide the appropriate therapy to achieve the recommended LDL-C levels of < 100 mg/dL or a more than 50% reduction for patients with FH in Japan.

Treatment goal attainment in children with familial hypercholesterolemia: A cohort study of 302 children in Norway

Consensus statements recommend that statin treatment in children with heterozygous familial hypercholesterolemia (FH) should be considered from 8 to 10years of age. Although these recommendations are well known, less is known about actual treatment and treatment goal attainment in children with FH. The objective of the study was to investigate if children with FH were treated according to current recommendations. Retrospective collection of data from medical records of 302 children below 18years visiting the Lipid Clinic, Oslo University hospital, during 2014 to2016. Ninety-nine percent had a genetically verified FH diagnosis. Mean age (standard deviation) at diagnosis, age at first visit, and time followed at the clinic was 8.5 (3.2), 9.5 (2.9), and 4.4 (2.7) years, respectively. Mean pretreatment low-density lipoprotein cholesterol (LDL-C) was 5.4 (1.4) mmol/L. Mean age at start of lipid-lowering therapy (LLT) was 12.5 (2.0) years, with no significant difference between girls and boys. LLT, mainly statins, was used by 177 (59%) children at their last visit. LDL-C in children treated with LLT was 3.6 (1.2) mmol/L (38% reduction from pretreatment, P<.001). A treatment goal of LDL-C ≤3.5mmol/L was achieved by 43% of all children, by 58% of the children on LLT, and by 22% of children not on LLT. Mean age at initiation of LLT is above the recommended 10years of age and many children did not achieve the LDL-C treatment goal, even with follow-up at a dedicated lipid clinic. Earlier diagnosis and more frequent follow-ups are warranted.

Reaching low-density lipoprotein cholesterol treatment targets in stable coronary artery disease: Determinants and prognostic impact

Low-density lipoprotein cholesterol (LDL-C) reduction is an integral part of the management of patients with coronary artery disease (CAD). To assess attainment of LDL-C goals during long-term treatment of patients with stable CAD, and to determine predictors of goal attainment and the prognostic impact of reaching LDL-C<70mg/dL (1.8mmol/L) in a real-life setting. Data were obtained for 4080 outpatients with stable CAD included in the multicentre CORONOR study. Five-year follow-up was achieved for 3991 (97.8%) patients. At inclusion, a recent (<1 year) measurement of LDL-C was available in 3757 (92.1%) patients. LDL-C<70mg/dL was reached by 885 (23.6%) patients. Independent predictors of LDL-C<70mg/dL were diabetes mellitus, statin treatment, treatment with renin-angiotensin system inhibitors, previous myocardial infarction and short time since last coronary event. The adjusted hazard ratio (HR) for the composite endpoint (cardiovascular death, myocardial infarction, ischemic stroke or coronary revascularization) during the 5-year follow-up was 1.31 (95% confidence interval [CI]: 1.09-1.58; P=0.004) for LDL-C≥70mg/dL versus<70mg/dL. When compared with patients with LDL-C<70mg/dL, the adjusted HRs for LDL-C 70-99mg/dL and ≥100mg/dL (2.6mmol/L) were 1.27 (95% CI: 1.05-1.55; P=0.016) and 1.38 (95% CI: 1.12-1.70; P=0.003), respectively. When LDL-C was used as a continuous variable, the adjusted HRs for increases of 10mg/dL (0.3mmol/L) and 1mmol/L were 1.05 (95% CI: 1.03-1.08) and 1.21 (95% CI: 1.10-1.33), respectively. In this observational study, only a minority of stable CAD patients had LDL-C<70mg/dL. The patients who reached their LDL-C goal had the lowest risk of cardiovascular events.

Suboptimal achievement of low-density lipoprotein cholesterol targets in French patients with coronary heart disease. Contemporary data from the DYSIS II ACS/CHD study

European guidelines recommend a low-density lipoprotein cholesterol (LDL-C) target of<1.8mmol/L (70mg/dL), and/or a≥50% reduction when the target level cannot be reached, for patients at very high cardiovascular risk, and high-potency lipid-lowering therapy (LLT) in patients with an acute coronary syndrome (ACS). To document the prevalence of lipid abnormalities and the achievement of lipid targets among patients surviving an ACS and in patients with stable coronary heart disease (CHD), using data from the DYSIS II study. DYSIS II was an observational cross-sectional study conducted in 21 countries (2012-2014). We report data from the French cohort, comprising patients hospitalized with an ACS and patients diagnosed with stable CHD. Data on patient characteristics, risk factors, treatments and lipid profile were collected. LDL-C target achievement was assessed based on the European guidelines endorsed by the French Society of Cardiology. Of the 468 ACS patients, 277 (59.2%) were receiving LLT at admission to hospital; 22.6% were hospitalized for a recurrent event. Statins were used in 96.6% (450/466) of patients at discharge and in 95.1% (310/326) at 120-day follow-up, at which time 50.6% (80/158) of patients with available data achieved the LDL-C goal. Most of the 436 patients with stable CHD (97.2%) were on LLT (56.8% on high-intensity therapy); 29.2% of patients on LLT met the LDL-C treatment target<1.8mmol/L (70mg/dL). These observational data show the progress made in the treatment of ACS from the acute phase up to 3 months, and highlight key areas for improvement in the prevention of recurrent events in patients with CHD in France. The use of higher intensity or combination LLT as recommended in secondary prevention are needed to increase the achievement of LDL-C treatment targets and reduce the risk of morbidity and mortality due to CHD.

Clinical determinants and treatment gaps in familial hypercholesterolemia: Data from a multi-ethnic regional health service.

Background Familial hypercholesterolemia is characterized by markedly increased low-density lipoprotein cholesterol and risk for premature atherosclerotic cardiovascular disease. Models of care vary and reflect differing health policies and resources. The availability of electronic databases may enable better identification and assessment of familial hypercholesterolemia in the community. Methods A regional healthcare database was utilized to identify patients with a high probability of familial hypercholesterolemia, clinically defined by age-dependent-peak low-density lipoprotein cholesterol cutoffs and exclusion of secondary causes of severe hypercholesterolemia. Clinical characteristics, low-density lipoprotein cholesterol goal attainment, and treatment gaps were investigated. Results Probable familial hypercholesterolemia was diagnosed in 1932 of 685,314 individuals (1:355; median age 47 years). Atherosclerotic cardiovascular disease was present in 16.3% of adults (38% in males aged 50-74 years). Median peak low-density lipoprotein cholesterol was 264 mg/dl (interquartile range 252-288). Statins and/or ezetimibe were prescribed to 83% of patients and high-intensity statins to 53%, whereas prescriptions were filled in 57% and 40% cases respectively over the last six months, p < 0.001. Treatment gaps were wider among ethnic minorities, younger individuals, and those without atherosclerotic cardiovascular disease. Low-density lipoprotein cholesterol < 100 mg/dl was attained in 10.1% overall and 28.7% of those with atherosclerotic cardiovascular disease. Predictors of low-density lipoprotein cholesterol goal attainment included recent issue of high-intensity statins, presence of atherosclerotic cardiovascular disease, diabetes, older age and lack of smoking. Conclusions The population with high probability for familial hypercholesterolemia was characterized by low attainment of low-density lipoprotein cholesterol treatment goals despite high prescription rates of lipid-lowering medications. Low utilization of intensified therapies, non-adherence, and ethnic disparities were contributing factors. These findings emphasize the need to improve awareness and quality of care of familial hypercholesterolemia in the community.

Impact of combined lipid lowering and blood pressure control on coronary plaque: myocardial ischemia treated by percutaneous coronary intervention and plaque regression by lipid lowering and blood pressure controlling assessed by intravascular ultrasonography (MILLION) study.

The aim of the study was to elucidate the aggressive reduction of both low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) reduced coronary atherosclerotic plaque volume compared with a standard treatment of LDL-C and BP in Japanese patients with coronary artery disease (CAD). This study is a prospective, randomized, and open-labelled with a blind-endpoint evaluation study. A total of 97 patients (81 men, mean age 62.0±9.6) with CAD undergoing intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) were randomized, and 68 patients had IVUS examinations at baseline and at 18-24months follow-up. Patients were randomly assigned to standard or aggressive strategies targeting LDL-C and a BP of 100mg/dL and 140/90mmHg vs. 70mg/dL and 120/70mmHg, respectively. The primary endpoint was the percent change in coronary plaque volume. Both standard and aggressive strategies succeeded to achieve target levels of LDL-C and BP; 74.9±14.7 vs. 63.7±11.9mg/dL (NS) and 124.1±9.4/75.8±7.7 vs. 113.6±9.6/65.8±9.4mmHg (systolic BP; NS, diastolic BP; p<0.05), respectively. Both groups showed a significant reduction in the coronary plaque volume of -9.4±10.7% and -8.7±8.6% (NS) in standard and aggressive therapies, respectively. Both standard and aggressive intervention significantly regressed coronary plaque volume by the same degree, suggesting the importance of simultaneous reductions of LDL-C and BP for prevention of CAD.

Correlates of Achieving Statin Therapy Goals in Children and Adolescents with Dyslipidemia

To determine the real-world effectiveness of statins and impact of baseline factors on low-density lipoprotein cholesterol (LDL-C) reduction among children and adolescents. We analyzed data prospectively collected from a quality improvement initiative in the Boston Children's Hospital Preventive Cardiology Program. We included patients ≤21 years of age initiated on statins between September 2010 and March 2014. The primary outcome was first achieving goal LDL-C, defined as <130 mg/dL, or <100 mg/dL with high-level risk factors (eg, diabetes, etc). Cox proportional hazards models were used to assess the impact of baseline clinical and lifestyle factors. Among the 1521 pediatric patients evaluated in 3813 clinical encounters over 3.5 years, 97 patients (6.3%) were started on statin therapy and had follow-up data (median age 14 [IQR 7] years, 54% were female, and 24% obese, 62% with at least one lifestyle risk factor). The median baseline LDL-C was 215 (IQR 78) mg/dL, and median follow-up after starting statin was 1 (IQR 1.3) year. The cumulative probability of achieving LDL-C goal within 1 year was 60% (95% CI 47-69). A lower probability of achieving LDL-C goals was associated with male sex (HR 0.5 [95% CI 0.3-0.8]) and higher baseline LDL-C (HR 0.92 [95% CI 0.87-0.98] per 10 mg/dL), but not age, body mass index percentile, lifestyle factors, or family history. The majority of pediatric patients started on statins reached LDL-C treatment goals within 1 year. Male patients and those with greater baseline LDL-C were less likely to be successful and may require increased support.

LDL-Cholesterol: Standards of Treatment 2016: A German Perspective.

Decreasing low-density lipoprotein cholesterol (LDL-C) is one of the few established and proven principles for the prevention and treatment of atherosclerosis. The higher the individual cardiovascular risk, the higher the benefit of lipid-lowering pharmacotherapy. Therefore, treatment options are chosen based on a patient's total cardiovascular risk. The latter depends not only on the levels of LDL-C but also on the presence of cardiovascular disease (CVD) and on the number and severity of other risk factors. Current guidelines recommend the lowering of LDL-C to 115mg/dl (3mmol/l) in patients with low and moderate risk. The LDL-C treatment target is <100mg/dl (2.6mmol/l) for patients at high risk and<70mg/dl (1.8mmol/l) for patients at very high risk. Although lifestyle measures remain a fundamental part of treatment, many patients require drug therapy to achieve their LDL-C targets. Statins are the drugs of choice, with other options including ezetimibe and the newly available monoclonal antibodies against PCSK9 (proprotein convertase subtilisin/kexin type 9). In some cases, bile acid-binding sequestrants and fibrates can also be considered. Nicotinic acid is no longer available in Germany. PCSK9 antibodies decrease LDL-C about 50-60% and are well tolerated. Their effects on clinical endpoints are being investigated in large randomized trials. The aim of the present review is to summarize the current guidelines and treatment options for hypercholesterolemia. Moreover, we provide an appraisal of PCSK9 antibodies and propose their use in selected patient populations, particularly in those at very high cardiovascular risk whose LDL-C levels under maximally tolerated lipid-lowering therapy are significantly over their treatment target.

Correlation between pretreatment serum LDL-cholesterol levels and prognosis in nasopharyngeal carcinoma patients.

PurposeTo investigate the correlations between long-term survival outcomes in patients with nasopharyngeal carcinoma (NPC) and pretreatment serum low-density lipoprotein cholesterol (LDL-C) levels.Patients and methodsBetween January 2008 and December 2011, 935 patients with newly diagnosed NPC who were treated with intensity-modulated radiation therapy were included in this retrospective clinical analysis. Patients were divided into two groups based on pretreatment LDL-C levels: normal LDL-C (≤3.64 mmol/L; n=816) and elevated LDL-C (>3.64 mmol/L; n=119). Associations between pretreatment LDL-C levels and treatment outcome were analyzed by univariate and multivariate analyses.ResultsThe overall patient follow-up rate was 95.1%, and 726 patients received more than 5 years of follow-up. Five-year overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) rates of the entire patient population were 87.1%, 91.1%, and 87.2%, respectively. Rates of 5-year OS, LC, and DMFS for the elevated versus normal LDL-C groups were 77.0% vs 89.1% (P<0.001), 85.8% vs 91.9% (P=0.041), and 81.1% vs 88.1% (P=0.038), respectively. Compared with normal LDL-C levels, elevated LDL-C levels were identified as an independent prognostic factor of a poorer OS (hazard ratio [HR] =2.171; 95% confidence interval [CI] =1.424–3.309), LC rate (HR =1.762; 95% CI =1.021–3.942), and DMFS (HR =1.594; 95% CI =1.003–2.532).ConclusionThis study found that elevated pretreatment LDL-C levels are negative prognostic indicators of NPC. Elevated LDL-C levels may be useful indicators of locoregional control and distant metastasis in NPC patients.

Clinical and molecular characteristics of homozygous familial hypercholesterolemia patients: Insights from SAFEHEART registry

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder associated with very high levels of cholesterol, accelerated atherosclerosis and very premature death, often secondary to occlusion of the coronary ostia by supravalvular atheroma in untreated individuals. To describe molecular and clinical characteristics of HoFH enrolled at SAFEHEART registry and to evaluate the role of the type of mutation in clinical expression. SAFEHEART is a registry of molecularly defined familial hypercholesterolemia patients. A standardized phone call is made every year for the follow-up. Patients with confirmed HoFH were selected. Molecular and clinical characteristics were analyzed. Thirty-four HoFH patients (27 true HoFH, 4 compound heterozygous familial hypercholesterolemia, and 3 autosomal recessive hypercholesterolemia) have been enrolled in the period 2004-2015. Twenty different mutations in LDLR gene have been detected. Sixteen patients carry defective mutations (DMs), and 15 carry null mutations (NMs). Only patients with NMs met low-density lipoprotein cholesterol (LDL-C) criteria for clinical diagnosis. Patients with NMs had higher untreated LDL-C levels (P<.0001), more aortic valve stenosis (P<.05), and lower age at first cardiovascular event (P<.05) compared to patients with DMs. In the follow-up, 1 liver transplant patient died and 3 cases underwent revascularization procedures. Eight cases started LDL apheresis and 1 case had a liver transplant. HoFH phenotypic expression is highly variable. These patients have high atherosclerotic coronary artery disease risk including aortic valve stenosis and do not achieve the LDL-C treatment goals with standard therapy.

Attainment of LDL-Cholesterol Treatment Goals in Patients With Familial Hypercholesterolemia: 5-Year SAFEHEART Registry Follow-Up

BackgroundFamilial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data on attainment of treatment targets; large registries that reflect real-life clinical practice can uniquely provide this information. ObjectivesWe sought to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients enrolled in a large national registry. MethodsThe SAFEHEART study (Spanish Familial Hypercholesterolemia Cohort Study) is a large, ongoing registry of molecularly defined patients with heterozygous FH treated in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was investigated in relation to use of lipid-lowering therapy (LLT). ResultsThe study recruited 4,132 individuals (3,745 of whom were ≥18 years of age); 2,752 of those enrolled were molecularly diagnosed FH cases. Mean follow-up was 5.1 ± 3.1 years; 71.8% of FH cases were on maximal LLT, and an LDL-C treatment target <100 mg/dl was reached by only 11.2% of patients. At follow-up, there was a significant increase in the use of ezetimibe, drug combinations with statins, and maximal LLT. The presence of type 2 diabetes mellitus, a defective allele mutation, ezetimibe use, and the absence of previous ASCVD were predictors of the attainment of LDL-C goals. ConclusionsDespite the use of intensified LLT, many FH patients continue to experience high plasma LDL-C levels and, consequently, do not achieve recommended treatment targets. Type of LDL-receptor mutation, use of ezetimibe, coexistent diabetes, and ASCVD status can bear significantly on the likelihood of attaining LDL-C treatment goals.

Method of LDL cholesterol measurement influences classification of LDL cholesterol treatment goals: clinical research study.

Low-density lipoprotein cholesterol (LDL-C) has been clearly associated with the risk of developing coronary heart disease. The best and most convenient method for determining LDL-C has come under increased scrutiny in recent years. We present comparisons of the Friedewald calculated LDL-C (C-LDL-C) and direct LDL-C (D-LDL-C) using 3 different homogenous assays. This highlights differences between the 2 methods of LDL-C measurement and how this affects the classification of samples into different LDL-C treatment goals as determined by the National Cholesterol Education Program Adult Treatment Panel III guidelines thus potentially affecting treatment strategies. Lipid profiles of a total of 2208 clinic patients were retrieved from the Central Arkansas VA Healthcare System clinical laboratory database. Samples studied were of 1-week period during the 3 periods studied: 2000 (period 1), 2002 (period 2), and 2005 (period 3). Different homogenous assays for D-LDL-C measurement were used for each of the 3 periods. There is a fundamental disagreement between D-LDL-C and C-LDL-C, although Pearson correlation coefficients are 0.93, 0.97, and 0.98 for periods 1, 2, and 3, respectively. Using the model for period 1, when C-LDL-C is 70 mg/dL, the predicted D-LDL-C is 95 mg/dL (36% higher). The differences between C-LDL-C and predicted D-LDL-C progressively decrease at higher LDL-C cut points. In the assay used in period 3, there are 290 samples with D-LDL-C values between 100 and 130 mg/dL. Of these, only 182 samples show agreement with C-LDL-C values, whereas 90 samples with a D-LDL-C in the 100- to 130-mg/dL range are in the 70- to 100-mg/dL range using the C-LDL-C assay. Although the κ statistics suggests the LDL-C measures have relatively high levels of agreement, the significant generalized McNemar tests (P < 0.01) provide additional evidence of disagreement between C-LDL-C and D-LDL-C during all the 3 periods. Our results highlight D-LDL-C measurements using 3 different assays during 3 different periods. In all assays, there is a substantial lack of agreement between D-LDL-C and C-LDL-C, which, in most cases, resulted in higher D-LDL-C values than C-LDL-C. This leads to clinically significant misclassification of patient's LDL-C to a different LDL-C treatment goal, which would potentially result in more drug usage, thus exposing patients to more potential adverse effects and at a much greater cost with little evidence of benefit.

Statin Treatment by Low-Density Lipoprotein Cholesterol Levels in Patients With Non–ST-Segment Elevation Myocardial Infarction/Unstable Angina Pectoris (from the CRUSADE Registry)

Elevated low-density lipoprotein cholesterol (LDL-C) is associated with increased risk of myocardial infarction and is a target for disease prevention. The association between initial LDL-C and statin treatment in patients with non-ST-segment elevation myocardial infarction (NSTEMI)/unstable angina pectoris (UAP) has not been well characterized. We explored detailed LDL-C levels and statin treatment in 22,938 patients with NSTEMI/UAP enrolled in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines Registry (2003 to 2006). Patients reporting home statin use or previous cardiovascular disease were excluded. We examined statin receipt at discharge across 4 categories of baseline LDL-C: very low (<70mg/dl), low (70 to 99mg/dl), high (100 to 129mg/dl), and very high (≥130mg/dl). The largest proportion of patients had LDL-C ≥130mg/dl (32.6%), followed by LDL-C 100 to 129mg/dl (32.1%), LDL-C 70 to 99mg/dl (24.9%), and LDL-C <70mg/dl (10.4%). Compared with high LDL-C categories, patients in the lowest LDL-C category had their first NSTEMI/UAP event at a significantly older age and had higher rates of other cardiovascular risk factors (including hypertension and diabetes) but were less likely to have a family history of coronary artery disease. Overall, 80.3% of eligible patients with NSTEMI/UAP received statins at discharge, ranging from 63.8% in those with very low LDL-C (<70mg/dl) to 88.1% in those with very high LDL-C (>130mg/dl). In conclusion, >1/3 of patients with NSTEMI/UAP had an LDL-C level <100. Those with low LDL-C were older, had more co-morbidities, and were less likely to be prescribed a statin at discharge than those with higher LDL-C.

PCSK9 inhibition: current concepts and lessons from human genetics.

Low-density lipoprotein cholesterol (LDL-C) plays a central role in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Statins are the cornerstone of therapy for the treatment of elevated LDL-C and for the primary and secondary prevention of ASCVD. However, some patients are intolerant of statins or are unable to achieve acceptable lipid levels on statin-based regimens alone. Proprotein convertase subtilisin/kexin type 9 (PCSK9) serves as an important regulator of hepatocyte LDL receptor expression and degradation, and recent genetic studies have highlighted the critical role of PCSK9 in human disease. Gain-of-function mutations in PCSK9 are associated with familial hypercholesterolemia, whereas loss-of-function mutations are protective against ASCVD. Therefore, PCSK9 inhibition offers a promising supplement or alternative to statin therapy in the reduction of LDL-C. Numerous phase II and III randomized control trials have demonstrated the tolerability of monoclonal antibodies against PCSK9 and their efficacy in lowering LDL-C by an additional 40-70%. In this article, we review the growing role of PSCK9 inhibition in LDL-C reduction for diverse patient populations.

Centralized Pan-Middle East Survey on the Under-Treatment of Hypercholesterolemia: Results from the CEPHEUS Study in Egypt.

BackgroundCardiovascular disease is a major cause of morbidity and mortality; however, the risks associated with this disease can be reduced by targeting circulating low-density lipoprotein cholesterol (LDL-C) with lipid-lowering drugs, as recommended in many treatment guidelines. Their effectiveness for hypercholesterolemia management depends on appropriate use in at-risk patients. Observational studies have shown varying adherence to national and international guidelines on reaching LDL-C treatment goals.MethodsThe Centralized Pan-Middle East Survey on the under-treatment of hypercholesterolemia (CEPHEUS) study observed the current management of hypercholesterolemia in patients on lipid-lowering drugs in seven Middle Eastern countries, and results from 1,043 patients in Egypt are presented here.ResultsOverall, less than 50% of patients achieved their LDL-C treatment goal, with patients at higher risk of a cardiovascular event being less likely to attain their target. Nearly, three-quarters of patients in this study were considered high or very high risk, with only 10% of high-risk patients reaching their treatment goal.ConclusionsManagement of hypercholesterolemia in Egypt is comparatively worse than the average for similar countries in the region, and many patients with high risk of CVD are not being effectively treated. Initiatives to improve physicians’ management of these patients and patient compliance to treatment are urgently needed.FundingAstraZeneca, Cairo, Egypt.Electronic supplementary materialThe online version of this article (doi:10.1007/s40119-014-0031-x) contains supplementary material, which is available to authorized users.

Frequency of High-Risk Patients Not Receiving High-Potency Statin (from a Large Managed Care Database)

We examined trends in low-density lipoprotein cholesterol (LDL-C) goal attainment in high-risk patients and use of high-potency statins (HPS) in a large, managed-care database from 2004 to 2012. The 2013 American Heart Association/American College of Cardiology prevention guidelines recommend that subjects with atherosclerotic cardiovascular disease (ASCVD) should be prescribed HPS therapy, irrespective of LDL-C levels. Previous guidelines recommend an LDL-C target <70 mg/dl. Patients diagnosed with ASCVD based on International Classification of Diseases, Ninth Revision codes with ≥1 LDL-C test from January 2004 to December 2012 were identified in the Optum Insight database. Patients were identified as treated if they received lipid-lowering therapy (LLT) within 90 days of the LDL-C measurement and untreated if they did not receive LLT treatment. LLT treated patients were stratified into HPS users or non-HPS LLT users. There were 45,101 eligible patients in 2004 and 40,846 in 2012. The proportion of high-risk patients who were treated with LLT increased from 61.4% (2004) to 70.5% (2008) then remained relatively constant until 2012 (67.9%). Mean LDL-C values in treated patients decreased from 103.7 ± 32.1 (2004) to 90.8 ± 31.4 mg/dl (2012). The proportion of patients treated with HPS increased from 13% in 2004 to 26% in 2012. Although the proportion of treated high-risk patients who achieve LDL-C <70 mg/dl levels has increased sharply from 2004, approximately 3 of 4 patients still did not meet this target. Only 1/4 of ASCVD patients are on HPS. In conclusion, our findings highlight the need for renewed efforts to support guideline-based LDL-C treatment for high-risk patients.

Guías en el manejo de la dislipemia

The AHA/ACC 2013 guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease (ASCVD) in adults contains major differences with the previous ESC/EAS 2011 guidelines and the remaining international guidelines, which has generated major controversies. The AHA/ACC document has developed a new model for estimating cardiovascular risk for primary prevention which is not comparable with the SCORE recommended in the European guidelines. This guideline does not establish a fixed target for low-density lipoprotein cholesterol (LDLc). Instead, it identifies 4 major statin benefit groups at risk for the development ASCVD, who should receive low-, moderate-, and high-intensity statin therapy to reduce LCLc. In contrast, the European guidelines maintain LDLc as the main treatment target and non-high-density lipoprotein cholesterol as a secondary treatment target. The document recommends calculating cardiovascular risk for the overall treatment of patients with dyslipidemia according to 4 risk levels (low, moderate, high, and very high), establishes LDLc treatment targets, and recommends a statin-based therapeutic strategy and other, lipid-lowering strategies, aimed at achieving these targets.The American guidelines cannot be extrapolated to the European population. Target-based treatment, as recommended in the EAS/ESC guidelines, is the best strategy for Europe. In Spain, the Primary Care Guidelines of the Spanish Society of Family and Community Medicine (semFYC) and the Spanish Society of Primary Care Physicians (SEMERGEN) are based on the European recommendations. Finally, the Spanish Society of Arteriosclerosis (SEA), SEMERGEN, semFYC and the Spanish Society of General Medicine (SEMG) are reaching a consensus on the approach and management of patients with atherogenic dyslipidemia in primary care.