Median Low-density Lipoprotein Cholesterol Research Articles

Cardiovascular disease prevalence and insulin resistance in the Kyushu–Okinawa Population Study and the Framingham Offspring Study

Age-adjusted cardiovascular disease (CVD) prevalence rates are significantly lower in Japan than in the United States. Our aim was to compare CVD risk in participants in Fukuoka and Framingham. We measured glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL-C, and triglycerides in men and women from Fukuoka (n=1108), and age (median, 53years) and gender-matched subjects from Framingham (n=1101). Blood pressure, body mass index, use of medications, and history of CVD were also assessed. CVD prevalence rates were more than 6-fold higher in Framingham men and women than their Fukuoka counterparts (P<.001). Median body mass index, LDL-C, insulin levels, and insulin resistance assessment in Fukuoka men and women were significantly (P<.01) lower than in Framingham; however, diabetes prevalence in Fukuoka men was significantly (P<.01) higher than in Framingham men, whereas female rates were similar, as were levels of systolic blood pressure. High-density lipoprotein cholesterol and surprisingly small dense LDL-C levels were significantly (P<.001) higher in Fukuoka than in Framingham. Standard risk factors do not account for the large differences in CVD prevalence rates between the 2 populations, and population differences in insulin resistance may explain some of these differences. Our data are consistent with the concept that the CVD prevalence rate in a Japanese population is much lower than those observed in the United States, and that these differences cannot be explained by standard CVD risk factors, but may relate to marked population differences in insulin resistance.

CRT-600.07 Head to Head Efficacy of Alirocumab 75 and 150 mg vs Evolocumab 140 mg in Real World Patients

In 107 high-risk patients, 60% with cardiovascular disease (CVD), and with median low-density lipoprotein cholesterol (LDLC) 149 mg/dL despite maximum tolerated lipid lowering therapy (MTLT), we compared and contrasted efficacy-safety of Alirocumab (ALI 75mg, 150 mg) and Evolocumab (EVO 140 mg). We

Efficacy, safety, Low density lipoprotein cholesterol lowering, and calculated 10-year cardiovascular risk reduction of alirocumab and evolocumab in addition to maximal tolerated cholesterol lowering therapy: a post-commercialization study

BackgroundEfficacy and safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab (ALI) and evolocumab (EVO) have previously been evaluated through controlled clinical trials with selective patient groups. Post-commercially, in patients with heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC) lowering on maximal tolerated cholesterol lowering therapy, we assessed efficacy and safety of ALI and EVO.MethodsPost-commercially, we started 25 patients on ALI 75 mg, 15 on ALI 150 mg, and 32 on EVO 140 mg bi-weekly added to entry LDLC lowering regimen, with follow-up for a median 24 weeks. History, physical exam, demographics, and adverse event data were collected. Changes in LDLC and AHA and NIH calculated 10-year CVD risks were assessed on ALI and EVO.ResultsOf 72 patients, 25 had HeFH only, 25 CVD only, 22 had both, median age was 65 years, 63% females, 38% males, 86% Caucasian, 11% African-Americans, 17% diabetics, 63% on anti-hypertensives, and 7% smokers. At entry, 30 (42%) were on a statin and 42 (58%) could not tolerate any statins.At 24-weeks, median LDLC decreased on ALI 75 mg from 117 to 62 mg/dL (−54%), on ALI 150 mg from 175 to 57 mg/dL (−63%), and on EVO 140 mg from 165 to 69 mg/dL (−63%), p <0.0001 for all. Absolute and percent LDLC reduction did not differ (p >.05) between ALI 150 and EVO 140 mg, but were less on ALI 75 mg vs ALI 150 mg and EVO 140 mg (p <.05).Percent reductions in 10-year CVD risks by AHA and NIH calculators, respectively were ALI 75 mg −22 and −44%, ALI 150 mg −31 and −50%, and EVO 140 mg −29 and −56%, p ≤.002 for all.The three most common adverse events included flu-like myositis 10%, respiratory tract symptoms 8%, and injection site reaction 6%.ConclusionIn patients with HeFH and/or CVD, LDLC was lowered by 63% on EVO and ALI 150 mg, and 54% on ALI 75 mg. Adverse events were minimal and tolerable. ALI and EVO represent paradigm shifts in LDLC lowering. Long term, post-commercial safety and efficacy remain to be determined.

The role of specialized prevention clinics for the short term follow-up of acute coronary syndromes.

This study aimed to investigate the effect of specialized prevention clinics and standard clinics follow-ups on secondary protection after acute coronary syndrome (ACS) on cardiovascular risk factors. A total of 118 patients who received thrombolytic therapy after being diagnosed with ST-segment elevation myocardial infarction were followed up for 6 months. After ACS, patients in a specialized prevention clinic (Group 1) (n=67) and those in a standard clinic (Group 2) (n=51) were compared in terms of the change in their lifestyle, management of risk factors, and drug compliance. No significant difference was found between groups in terms of baseline clinical and laboratory findings except for triglyceride level (Group 1: median 174 mg/dL; Group 2: median 136 mg/dL; p=0.039). Six months after indexing, smoking cessation (72.4% vs. 50%, p=0.037), diet compliance (43% vs.19.6%, p=0.012), and exercise rates (31% vs. 13.7%, p=0.044) were significantly higher in Group 1. Although the weight control rate was higher in Group 1, no significant difference was noted between the groups (27% vs. 15.6%, p=0.219). The rate of systolic and diastolic blood pressures >140/90 mmHg was significantly higher in Group 2 (23.5% vs. 9%, p=0.029) at 6 months. The median low-density lipoprotein cholesterol (LDL-C) value was significantly lower in Group 1 patients (Group 1: 91 mg/dL; Group 2: 102 mg/dL; p=0.042). Moreover, the rate of LDL-C ≤70 mg/dL or ≥50% reduction compared with baseline was significantly higher in Group 1 (32.8% vs. 13.7%, p=0.016). Although the recommended treatments were similar in both groups, the statin use rate was significantly higher in Group 1 (95.5% vs. 80.3%, p=0.021) at 6 months. The results of the study showed that specialized prevention clinics were more effective during the management of cardiovascular risk factors after ACS.

Blood pressure and lipid profiles in adolescents with hypertensive parents

problem of increasing prevalence and causes high morbidityand mortality. It is found primarily in young males, with afamilial history of hypertension and/or cardiovascular disease.Examination of lipid profiles has been used to detect the risk ofhypertension in adolescents.Objective To compare blood pressure and lipid profiles inadolescents with and without a parental history of hypertension.Methods This cross-sectional study was conducted from January toFebruary 2012 on students from a senior high school in the TobaSamosir District, North Sumatera. Sixty-eight adolescents wereincluded, aged 15 to 18 years. Group I comprised 34 adolescentswith hypertensive parents, and group II comprised 34 adolescentswith normotensive parents. Subjects were selected based onquestionnaires. Subjects’ blood pressures were measured at rest.Three measurements were made in intervals of 10-15 minutes,then averaged for both systolic and diastolic blood pressures. Lipidprofiles were measured using the CardioCheck cholesterol testafter subjects had fasted for 12 hours.Results The median systolic blood pressures (SBP) in groupsI and II were 110 mmHg (range 93.3-123.3) and 106.7 mmHg(range 96.7-123.3), respectively, (P=0.584). The median diastolicblood pressures (DBP) were 73.3 mmHg (range 66.7-83.3) and71.7 mmHg (range 63.3-80.0), respectively, (P=0.953). Totalcholesterol and low-density lipoprotein cholesterol (LDL-C) levelsin group I were significantly higher than those levels in group II[median total cholesterol: 162.0 (range 158-170) vs. 159.0 (range150-170), respectively; (P=0.001); and mean LDL-C: 103.5 (SD3.72) vs. 99.1 (SD 4.63), respectively; (P=0.001). Multivariateanalysis revealed a correlation of moderate strength betweenparental history of hypertension and increased LDL-C (P&lt;0.001)in adolescents.Conclusion Adolescents with and without familial historyof hypertension have no significant median blood pressuredifferences. However, adolescents with hypertensive parents have afsignificantlyhigher median total cholesterol and mean LDL-C.Furthermore, we find a correlation between parental history ofhypertension and increased LDL-C in adolescents.

The influence of ApoE genotype on the lipid profile and lipoproteins during normal pregnancy in a Southern African population.

Pregnancy is associated with increases in fasting triglycerides and total cholesterol.1 ApoE isoforms are known to influence the concentration of cholesterol, with apoE2 homozygosity lowering and apoE4 homozygosity raising the cholesterol concentration compared with E3 homozygosity.2 The lipid profiles ApoE status and prevalence of small dense LDL species were evaluated for subjects attending an antenatal clinic. Samples from 690 women aged between 16 and 42 years of age were analyzed during and after pregnancy. The fasting plasma triglyceride concentration (in mmol/L) was significantly higher in pregnancy (median = 1.5, IQR 1.0-2.0 vs median = 0.6, IQR 0.5-0.8 respectively, p < 0.0001). Similarly, the total cholesterol (in mmol/L) was increased during pregnancy (median=4.1, IQR 3.6-4.7 vs median 3.5, IQR 3.1-3.5, respectively p=0.0167). The median LDL cholesterol and HDL cholesterol did not change. Higher proportions of small density LDL species were seen during pregnancy compared to after pregnancy. The distribution of the LDL species during pregnancy and 6 weeks post-partum were significantly different p<0.0001 with the smaller species being much higher during pregnancy. ApoE4 genotype was associated with increased total cholesterol and LDL cholesterol concentrations during pregnancy. Pregnancy results in a reversible remodeling of LDL to smaller species, the significance of which is unknown but may indicate a predisposition to atherosclerosis.

Dyslipidaemia and its treatment in patients with type 2 diabetes: A joint analysis of the German DIVE and DPV registries.

To compare lipid abnormalities in people with and without type 2 diabetes mellitus (T2DM) and to assess the effect of treatment. We combined data from the German DIVE (DIabetes Versorgungs-Evaluation) and DPV (Diabetes-Patienten-Verlaufsdokumentation) databases to produce a large cohort of people with T2DM. The characteristics of people receiving and not receiving lipid-modifying therapy (LMT) were compared, including demographics, cardiovascular (CV) risk factors and comorbidities. Lipid profiles were evaluated, and the achievement of recommended LDL cholesterol and non-HDL cholesterol targets was assessed. The effect on lipid levels in subgroups of patients aged ≥60 years, being obese or with CV disease was also investigated. A total of 363 949 people were included in the analysis. Of these, only 97 160 (26.7%) were receiving LMT. These individuals were older than those not receiving LMT, and comorbidities were more prevalent. Statins were the most commonly used agents (84.2%), with ezetimibe, fibrates and nicotinic acid taken by a small proportion of people. The median LDL cholesterol level was lower for the LMT group (100.5 vs 114.0 mg/dL; P < .001), as was the non-HDL cholesterol level (131.0 vs 143.1 mg/dL; P < .001), while the triglyceride level was higher (160.3 vs 152.0 mg/dL; P < .001). HDL cholesterol was lower in the LMT group for both men (41.0 vs 42.0 mg/dL; P < .001) and women (47.5 vs 48.0 mg/dL; P < .001). Elderly people were more likely to have achieved the target lipid levels, while obese people were less likely. For people with CV disease, there was a greater likelihood of achieving LDL, total and non-HDL cholesterol targets, but less chance of attaining a desired HDL cholesterol level. Dyslipidaemia was highly prevalent in this large population and management of lipid abnormalities was suboptimal. The distinct lipid profile of people with T2DM warrants further investigation into the use of non-statins in addition to statin LMT.

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.

The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial.

To examine the efficacy and safety of ezetimibe added to statin in patients with prior coronary artery bypass graft surgery (CABG) following hospitalization for an acute coronary syndrome (ACS). In the IMPROVE-IT trial, post-ACS patients with mean low density lipoprotein cholesterol (LDL-C) of 93.8 mg/dL at presentation were randomized to simvastatin/ezetimibe or simvastatin/placebo. The primary endpoint was cardiovascular death, major coronary event or stroke, and the median follow-up was 6 years. Efficacy and safety endpoints were examined by prior CABG status. Among 18 134 patients, 1684 (9.3%) had a prior CABG (median age 69 years, 82% male). During the trial, the median time-weighted LDL-C level was 55.0 mg/dL with simvastatin/ezetimibe vs. 69.9 mg/dL with simvastatin/placebo in patients with prior CABG (P < 0.001), and it was 53.6 mg/dL vs. 69.5 mg/dL, respectively, in patients without prior CABG (P < 0.001). The rate of the primary endpoint was higher in patients with vs. without prior CABG [56% vs. 32%, adj. hazard ratio 1.45, 95% confidence interval (CI) 1.33-1.58]. Patients with prior CABG receiving simvastatin/ezetimibe had an 8.8% (95% CI 3.1-14.6%) lower absolute risk over simvastatin/placebo in the primary endpoint, whereas patients without prior CABG had a 1.3% (95% CI 0-2.6%) lower absolute risk (P-interaction = 0.02). There were no between-group significant differences in safety endpoints. The clinical benefit of adding ezetimibe to statin appears to be enhanced in patients with prior CABG, supporting the use of intensive lipid lowering therapy in these high-risk patients following ACS.

Pharmacoeconomics of PCSK9 inhibitors in 103 hypercholesterolemic patients referred for diagnosis and treatment to a cholesterol treatment center.

BackgroundPCSK9 inhibitor therapy has been approved by the FDA as an adjunct to diet-maximal tolerated cholesterol lowering drug therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) with suboptimal LDL cholesterol (LDLC) lowering despite maximal diet-drug therapy. With an estimated ~24million of US hypercholesterolemic patients potentially eligible for PCSK9 inhibitors, costing ~ $14,300/patient/year, it is important to assess health-care savings arising from PCSK9 inhibitors vs ASCVD cost.MethodsIn 103 patients with HeFH, and/or ASCVD and/or suboptimal LDLC lowering despite maximally tolerated diet-drug therapy, we assessed pharmacoeconomics of PCSK9 inhibitor therapy with lowering of LDLC. For HeFH diagnosis, we applied Simon Broome’s or WHO Dutch Lipid Criteria (score >8). Estimates of direct and indirect costs for ASCVD events were calculated using American Heart Association (AHA), U.S. DHHS, Healthcare Bluebook, and BMC Health Services Research databases. We used the ACC/AHA 10-year ASCVD risk calculator to estimate 10-year ASCVD risk and estimated corresponding direct and indirect costs. Assuming a 50 % reduction in ASCVD events on PCSK9 inhibitors, we calculated direct and indirect health-care savings.ResultsWe started 103 patients (58 [56 %] women and 45 [44 %] men), on either alirocumab (62 %) or evolocumab (38 %), median age 63, BMI 29.0, and LDLC 149 mg/dl. Of the 103 patients, 28 had both HeFH and ASCVD, 33 with only ASCVD, 33 with only HeFH, and 9 had neither. Of the 103 patients, 61 had a first ASCVD event at median age 55 and on best tolerated cholesterol-lowering therapy median LDLC was 137 mg/dl. In these 61 patients, total direct costs attributable to ASCVD were $8,904,361 ($4,328,623 direct, $4,575,738 indirect), the median 10-year risk of a new CVD event was calculated to be 13.1 % with total cost $1,654,758. Assuming a 50 % reduction in ASCVD events on PCSK9 inhibitors in our 61 patients, $4,452,180 would have been saved in the past; and future 10-year savings would be $1,123,345.ConclusionIn the 61 CVD patients, net costs/patient/year were estimated to be $7,000 in the past, with future 10-year intervention net costs/patient/year being $12,459, both below the $50,000/year quality adjusted life-year gained by PCSK9 inhibitor therapy.

Treatment Gaps in Adults With Heterozygous Familial Hypercholesterolemia in the United States: Data From the CASCADE-FH Registry.

Cardiovascular disease burden and treatment patterns among patients with familial hypercholesterolemia (FH) in the United States remain poorly described. In 2013, the FH Foundation launched the Cascade Screening for Awareness and Detection (CASCADE) of FH Registry to address this knowledge gap. We conducted a cross-sectional analysis of 1295 adults with heterozygous FH enrolled in the CASCADE-FH Registry from 11 US lipid clinics. Median age at initiation of lipid-lowering therapy was 39 years, and median age at FH diagnosis was 47 years. Prevalent coronary heart disease was reported in 36% of patients, and 61% exhibited 1 or more modifiable risk factors. Median untreated low-density lipoprotein cholesterol (LDL-C) was 239 mg/dL. At enrollment, median LDL-C was 141 mg/dL; 42% of patients were taking high-intensity statin therapy and 45% received >1 LDL-lowering medication. Among FH patients receiving LDL-lowering medication(s), 25% achieved an LDL-C <100 mg/dL and 41% achieved a ≥50% LDL-C reduction. Factors associated with prevalent coronary heart disease included diabetes mellitus (adjusted odds ratio 1.74; 95% confidence interval 1.08-2.82) and hypertension (2.48; 1.92-3.21). Factors associated with a ≥50% LDL-C reduction from untreated levels included high-intensity statin use (7.33; 1.86-28.86) and use of >1 LDL-lowering medication (1.80; 1.34-2.41). FH patients in the CASCADE-FH Registry are diagnosed late in life and often do not achieve adequate LDL-C lowering, despite a high prevalence of coronary heart disease and risk factors. These findings highlight the need for earlier diagnosis of FH and initiation of lipid-lowering therapy, more consistent use of guideline-recommended LDL-lowering therapy, and comprehensive management of traditional coronary heart disease risk factors.

Abstract 613: Cardiovascular Disease Prevalence and Risk Factors in Japanese and American Populations

Cardiovascular disease (CVD) prevalence is known to be lower in Japan than in the United States. In this international cohort-comparative study, we compared CVD prevalence rates and risk factors in Fukuoka, Japan and in Framingham, United States. Using plasma samples obtained after an overnight fast from men and women in Fukuoka (n=1108) and age (median, 53 years), gender and menopausal status matched subjects in Framingham (n=1101), we measured plasma glucose, insulin, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), and triglycerides. Blood pressure, body mass index (BMI), use of medications, and history of CVD were also assessed. CVD prevalence rates were 2.1% and 1.0%, respectively, in Fukuoka men and women, and were more than 6 folder higher (both P&lt;0.001) at 13.2% and 8.6%, respectively, in Framingham men and women. Median BMI, LDL-C, insulin levels and insulin resistance in men and women in Fukuoka were all significantly (P&lt;0.01) lower than those in their Framingham counterparts. However the diabetes prevalence in Fukuoka men was significantly (P&lt;0.01) higher than that observed in Framingham men, while female rates were similar, as were levels of systolic blood pressure. Smoking rates were lower in Fukuoka women, but were higher in Fukuoka men as compared to their Framingham counterparts. HDL-C and surprisingly sdLDL-C levels were significantly (P&lt;0.001) higher in Fukuoka subjects than in Framingham subjects. Based on the results, the estimated 10 year risk of atherosclerotic cardiovascular disease, using the new American College of Cardiology/American Heart Association risk calculator, were 6.9% and 2.3%, respectively, for Framingham men and women, while these values for Fukuoka men and women were 7.4% and 1.7%, respectively. Only the risk estimates in women were significantly different (P&lt;0.001). Our data are consistent with prior studies indicating that CVD prevalence rates in Japan are lower than those in the United States, and that CVD risk algorithms for the United States markedly overestimate CVD risk in Japan. The markedly lower levels of insulin and insulin resistance in Japanese subjects may account for some of the population differences in CVD prevalence and risk.

Percent reduction in LDL cholesterol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents.

Current statin guidelines in Europe and Canada advocate achieving a fixed LDL target or the attainment of a ≥50% reduction in low-density lipoprotein cholesterol (LDLC), while current US guidelines advocate the use of statin therapies that reduce LDLC by <50% (moderate intensity) or ≥50% (high intensity). Data are limited, however, linking the achievement of these % reduction thresholds to subsequent cardiovascular outcomes particularly for contemporary high-intensity regimens. In a randomized trial of 17 082 initially healthy men and women with median baseline LDLC of 108 mg/dL (interquartile range 94-119), we (i) used waterfall plots to assess the variability in LDLC response to rosuvastatin 20 mg daily and (ii) evaluated the impact of reaching ≥50% reductions in LDLC on risk of developing the first cardiovascular events. Among rosuvastatin allocated participants, 3640 individuals (46.3%) experienced an LDLC reduction ≥50%; 3365 individuals (42.8%) experienced an LDLC reduction >0 but <50%; and 851 individuals (10.8%) experienced no reduction or an increase in LDLC compared with baseline. These % LDLC reductions directly related to the risks of first cardiovascular events; at trial completion, incidence rates for the primary endpoint were 11.2, 9.2, 6.7, and 4.8 per 1000 person-years for those in the placebo, no LDLC reduction, LDLC reduction <50%, and LDLC reduction ≥50% groups, respectively. Compared with placebo, the multivariable adjusted hazard ratios for sequentially greater on-treatment per cent reductions in LDLC were 0.91 (95%CI 0.54-1.53), 0.61 (95%CI 0.44-0.83), and 0.43 (95%CI 0.30-0.60) (P < 0.00001). Similar relationships between % reduction and clinical outcomes were observed in analyses focusing on non-HDLC or apolipoprotein B. As documented for low- and moderate-intensity regimens, variability in % LDLC reduction following high-intensity statin therapy is wide yet the magnitude of this % reduction directly relates to efficacy. These data support guideline approaches that incorporate % reduction targets for statin therapy as well as absolute targets, and might provide a structure for the allocation of emerging adjunctive lipid-lowering therapies such as PCSK9 inhibitors should these agents prove broadly effective for cardiovascular event reduction.

Changes of coronary plaque composition correlate with C-reactive protein levels in patients with ST-elevation myocardial infarction following high-intensity statin therapy

ObjectivesLevels of inflammatory biomarkers associate with changes of coronary atheroma burden in statin-treated patients with stable coronary artery disease. This study sought to determine changes of plaque composition in vivo in relation to high-sensitivity C-reactive protein (hs-CRP) levels in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin therapy. MethodsThe IBIS-4 study performed serial (baseline and 13-month), 2-vessel intravascular ultrasound (IVUS) and radiofrequency-IVUS of the non-infarct-related arteries in patients with STEMI treated with high-intensity statin therapy. The present analysis included 44 patients (80 arteries) with serial measurements of hs-CRP. ResultsAt follow-up, median low-density lipoprotein cholesterol (LDL-C) levels decreased from 126 to 77 mg/dl, HDL-C increased from 44 to 47 mg/dl, and hs-CRP decreased from 1.6 to 0.7 mg/L. Regression of percent atheroma volume (−0.99%, 95% CI −1.84 to −0.14, p = 0.024) was accompanied by reduction of percent fibro-fatty (p = 0.04) and fibrous tissue (p < 0.001), and increase in percent necrotic core (p = 0.006) and dense calcium (p < 0.001). Follow-up levels of hs-CRP, but not LDL-C, correlated with changes in percent necrotic core (p = 0.001) and inversely with percent fibrous tissue volume (p = 0.008). Similarly, baseline-to-follow-up change of hs-CRP correlated with the change in percent necrotic core volume (p = 0.02). ConclusionsIn STEMI patients receiving high-intensity statin therapy, stabilization of VH-IVUS–defined necrotic core was confined to patients with lowest on-treatment levels and greatest reduction of hs-CRP. Elevated CRP levels at follow-up may identify progression of high-risk coronary plaque composition despite intensive statin therapy and overall regression of atheroma volume.

Discordance Between Apolipoprotein B and LDL-Cholesterol in Young Adults Predicts Coronary Artery Calcification: The CARDIA Study

BackgroundHigh levels of apolipoprotein B (apoB) have been shown to predict atherosclerotic cardiovascular disease (CVD) in adults even in the context of low levels of low-density lipoprotein cholesterol (LDL-C) or non–high-density lipoprotein cholesterol (non–HDL-C). ObjectivesThis study aimed to quantify the associations between apoB and the discordance between apoB and LDL-C or non–HDL-C in young adults and measured coronary artery calcium (CAC) in midlife. MethodsData were derived from a multicenter cohort study of young adults recruited at ages 18 to 30 years. All participants with complete baseline CVD risk factor data, including apoB and year 25 (Y25) CAC score, were entered into this study. Presence of CAC was defined as having a positive, nonzero Agatston score as determined by computed tomography. Baseline apoB values were divided into tertiles of 4 mutually exclusive concordant/discordant groups, based on median apoB and LDL-C or non–HDL-C. ResultsAnalysis included 2,794 participants (mean age: 25 ± 3.6 years; body mass index: 24.5 ± 5 kg/m2; and 44.4% male). Mean lipid values were as follows: total cholesterol: 177.3 ± 33.1 mg/dl; LDL-C: 109.9 ± 31.1 mg/dl; non–HDL-C: 124.0 ± 33.5 mg/dl; HDL-C: 53 ± 12.8 mg/dl; and apoB: 90.7 ± 24 mg/dl; median triglycerides were 61 mg/dl. Compared with the lowest apoB tertile, higher odds of developing Y25 CAC were seen in the middle (odds ratio [OR]: 1.53) and high (OR: 2.28) tertiles based on traditional risk factor–adjusted models. High apoB and low LDL-C or non–HDL-C discordance was also associated with Y25 CAC in adjusted models (OR: 1.55 and OR: 1.45, respectively). ConclusionsThese data suggest a dose–response association between apoB in young adults and the presence of midlife CAC independent of baseline traditional CVD risk factors.

Statin Intolerance Because of Myalgia, Myositis, Myopathy, or Myonecrosis Can in Most Cases be Safely Resolved by Vitamin D Supplementation.

Background:Low serum vitamin D can cause myalgia, myositis, myopathy, and myonecrosis. Statin-induced myalgia is a major and common cause of statin intolerance. Low serum vitamin D and statins, additively or synergistically, cause myalgia, myositis, myopathy, and/or myonecrosis. Statin-induced myalgia in vitamin D deficient patients can often be resolved by vitamin D supplementation, normalizing serum vitamin D levels.Aims:In 74 men and 72 women (age 59 ± 14 years) intolerant to ≥2 statins because of myalgia, myositis, myopathy, or myonecrosis and found to have low (<32 ng/mL) serum vitamin D, we prospectively assessed whether vitamin D supplementation (vitamin D2: 50,000-100,000 units/week) to normalize serum vitamin D would allow successful rechallenge therapy with statins.Materials and Methods:Follow-up evaluation on vitamin D supplementation was done on 134 patients at 6 months (median 5.3), 103 patients at 12 months (median 12.2), and 82 patients at 24 months (median 24).Results:Median entry serum vitamin D (22 ng/mL, 23 ng/mL, and 23 ng/mL) rose at 6 months, 12 months, and 24 months follow-up to 53 ng/mL, 53 ng/mL, and 55 ng/mL, respectively, (P < .0001 for all) on vitamin D therapy (50,000-100,000 units/week). On vitamin D supplementation, serum vitamin D normalized at 6 months, 12 months, and 24 months follow-up in 90%, 86%, and 91% of the patients, respectively. On rechallenge with statins while on vitamin D supplementation, median low-density lipoprotein cholesterol (LDLC) fell from the study entry (167 mg/dL, 164 mg/dL, and 158 mg/dL) to 90 mg/dL, 91 mg/dL, and 84 mg/dL, respectively, (P < .0001 for all). On follow-up at median 6 months, 12 months, and 24 months on statins and vitamin D, 88%, 91%, and 95% of the previously statin-intolerant patients, respectively, were free of myalgia, myositis, myopathy, and/or myonecrosis.Conclusions:Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis associated with low serum vitamin D can be safely resolved by vitamin D supplementation (50,000-100,000 units /week) in most cases (88-95%).

Abstract 19949: Attainment of Lipid Levels in Patients at High Cardiovascular Risk: Results from a U.S. Managed Care Population Study

Background: Current, generalizable data on low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) as well as triglyceride (TG) levels are necessary to guide health policy decisions, guideline recommendations and treatment innovation. While LDL-C and non-HDL-C are established targets, TG elevations of 150-500 mg/dL and &gt;500 mg/dL can contribute to CV disease and pancreatitis risk, respectively. We evaluated attainment of these lipid measures in a large, managed care population in the US. Methods: The analysis included patients from the Optum Research Database meeting the following criteria: a valid lipid profile measurement in 2012 (i.e. “index date”); ≥20 years of age; continuous enrollment for≥ 2 years; and ≥1 high risk CV condition. Each patient was categorized into a mutually-exclusive category in the following hierarchy: acute coronary syndrome (ACS) within 12 months; stable coronary heart disease (CHD); ischemic stroke; peripheral arterial disease (PAD); and diabetes mellitus. Patients covered by a prescription on the index date or within 30 days were considered to be on treatment. Results: In total, 217,516 patients met the inclusion criteria. Median (Q1 to Q3) age was 61 (53 to 70) years, 51.6% were male, 10.7% were treated with intensive statins, 34.8% with less-intensive statins and 5.8% with nonstatin lipid-modifying therapy. Median LDL-C was 92 (72 to 116) mg/dL, non-HDL-C was 118 (96 to 145) mg/dL and TG was 120 (85 to 169) mg/dL in the overall cohort. The frequency of lipid level achievement is displayed by hierarchical disease state (TABLE). Conclusions: This study is the largest analysis of LDL-C, non-HDL-C and TG levels in a contemporary US managed care high risk population. Statins were underutilized, reflected by inadequate achievement of optimal LDL-C and non-HDL-C levels. While very high TG levels were infrequent, more optimal TG level were only achieved in about two-thirds of the population.

Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: Final baseline characteristics of the IMPROVE-IT study population

The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is evaluating the potential benefit for reduction in major cardiovascular (CV) events from the addition of ezetimibe versus placebo to 40 mg/d of simvastatin therapy in patients who present with acute coronary syndromes and have low-density lipoprotein cholesterol (LDL-C) ≤ 125 mg/dL. The primary composite end point is CV death, nonfatal myocardial infarction (MI), nonfatal stroke, rehospitalization for unstable angina (UA), and coronary revascularization (≥ 30 days postrandomization). The simvastatin monotherapy arm's LDL-C target is <70 mg/dL. Ezetimibe was assumed to further lower LDL-C by 15 mg/dL and produce an estimated ~8% to 9% treatment effect. The targeted number of events is 5,250. We enrolled 18,144 patients with either ST-segment elevation MI (STEMI, n = 5,192) or UA/non-ST-segment elevation MI (UA/NSTEMI, n = 12,952) from October 2005 to July 2010. Western Europe (40%) and North America (38%) were the leading enrolling regions. The STEMI cohort was younger and had a higher percentage of patients naive to lipid-lowering treatment compared with the UA/NSTEMI cohort. The UA/NSTEMI group had a higher prevalence of diabetes, hypertension, and prior MI. Median LDL-C at entry was 100 mg/dL for STEMI and 93 mg/dL for UA/NSTEMI patients. This trial is evaluating LDL-C lowering beyond previously targeted LDL-C levels. The results depend on achieving the desired separation of LDL-C with ezetimibe and on the assumption that ezetimibe's lowering of LDL-C will have similar event reduction efficacy as the LDL-C lowering from a statin. The results could affect future therapies and guidelines.

Discordance of Low-Density Lipoprotein (LDL) Cholesterol With Alternative LDL-Related Measures and Future Coronary Events

Low-density lipoprotein cholesterol (LDL-C) is the traditional measure of risk attributable to LDL. Non-high-density lipoprotein cholesterol (NHDL-C), apolipoprotein B (apoB), and LDL particle number (LDL-P) are alternative measures of LDL-related risk. However, the clinical utility of these measures may only become apparent among individuals for whom levels are inconsistent (discordant) with LDL-C. LDL-C was measured directly, NHDL-C was calculated, apoB was measured with immunoassay, and LDL-P was measured with nuclear magnetic resonance spectroscopy among 27 533 healthy women (median follow-up 17.2 years; 1070 incident coronary events). Participants were grouped by median LDL-C (121 mg/dL) and each of NHDL-C, apoB, and LDL-P. Discordance was defined as LDL-C greater than or equal to the median and the alternative measure less than the median, or vice versa. Despite high LDL-C correlations with NHDL-C, apoB, and LDL-P (r=0.910, 0.785, and 0.692; all P<0.0001), prevalence of LDL-C discordance as defined by median cut points was 11.6%, 18.9%, and 24.3% for NHDL-C, apoB, and LDL-P, respectively. Among women with LDL-C less than the median, coronary risk was underestimated for women with discordant (greater than or equal to the median) NHDL-C (age-adjusted hazard ratio, 2.92; 95% confidence interval, 2.33-3.67), apoB (2.48, 2.01-3.07), or LDL-P (2.32, 1.88-2.85) compared with women with concordant levels. Conversely, among women with LDL-C greater than or equal to the median, risk was overestimated for women with discordant (less than the median) NHDL-C (0.40, 0.29-0.57), apoB (0.34, 0.26-0.46), or LDL-P (0.42, 0.33-0.53). After multivariable adjustment for potentially mediating factors, including HDL cholesterol and triglycerides, coronary risk remained underestimated or overestimated by ≈20% to 50% for women with discordant levels. For women with discordant LDL-related measures, coronary risk may be underestimated or overestimated when LDL-C alone is used. http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

SMITH-LEMLI-OPITZ syndrome, caused by deficiency in the last step of cholesterol biosynthesis: The bristol UKGTN DHCR7 mutation service

SMITH-LEMLI-OPITZ syndrome, caused by deficiency in the last step of cholesterol biosynthesis: The bristol UKGTN DHCR7 mutation service