Fasting Low-density Lipoprotein Cholesterol Levels Research Articles

L-shaped association of plasma low-density lipoprotein cholesterol with atrial fibrillation recurrence after catheter ablation: a prospective cohort study

The association between plasma low-density lipoprotein cholesterol (LDL-C) and atrial fibrillation (AF) recurrence after catheter ablation remains unclear. We aimed to assess the relationship between preprocedural LDL-C and the AF recurrence in patients undergoing catheter ablation. The cohort study consecutively included AF patients who underwent de novo catheter ablation between April 2021 and January 2023 in the Second Affiliated Hospital of Nanchang University in Jiangxi Province, China. Patients were divided into quartiles based on their baseline fasting LDL-C level (Q1-Q4). Multivariable Cox proportional hazards models were used to evaluate the relationship between LDL-C and AF recurrence. Our analysis included the use of a generalized additive model and smooth curve fitting (penalized spline method), and two-piecewise Cox proportional hazards models, to address the nonlinearity between preprocedural LDL-C and AF recurrence. A total of 482 AF patients with de novo catheter ablation were enrolled, with a median follow-up period of 15.00 months, AF recurrence occurred in 96 (19.92%) patients. The relationship between preprocedural LDL-C and AF recurrence after ablation presented as an L-shape, and the inflection point for the curve was found at the LDL-C level of 3.20 mmol/L (Log likelihood ratio P = 0.031). The hazard ratios (HR) [(95% confidence intervals (CI)] for AF recurrence were 0.50 (0.33–0.74) and 2.11 (0.76–5.89) to the left and right of the inflection point, respectively. Lower LDL-C level is associated with increased AF recurrence risk after catheter ablation were consistent across all subgroups.

Assessing metabolic flexibility response to a multifibre diet: a randomised-controlled trial.

Metabolic flexibility (MetF), defined as the ability to switch between fat and glucose oxidation, is increasingly recognised as a critical marker for assessing responses to dietary interventions. Previously, we showed that the consumption of multifibre bread improved insulin sensitivity and reduced low-density lipoprotein cholesterol (LDLc) levels in overweight and obese individuals. As a secondary objective, we aimed to explore whether our intervention could also improve MetF. In this study, 39 subjects at cardiometabolic risk participated in a double-blind, randomised, crossover trial lasting 8 weeks, repeated twice. During each phase, participants consumed either 150 g of standard bread daily or bread enriched with a mixture of seven dietary fibres. MetF response was assessed using a mixed-meal tolerance test (MMTT), analysing changes in respiratory quotient (∆RQ) measured using indirect calorimetry. Although there were no significant differences in ∆RQ changes induced by dietary fibre between the two diets, these changes were positively correlated with postprandial triglyceride excursion (∆TG) at baseline. Subgroup analysis of baseline fasting and postprandial plasma metabolites was conducted to characterise MetF responders. These responders exhibited higher baseline fasting LDLc levels and greater post-MMTT ∆TG. In conclusion, although dietary fibres did not directly impact MetF in this study, our findings highlight potential determinants of MetF response, warranting further investigation in dedicated future interventions.

Clinical and Prognostic Value of Non-Fasting Lipoproteins and Apolipoproteins in Chinese Patients with Coronary Heart Disease.

Lipid profiles differ naturally between individuals and between populations. So far, the data relating to non-fasting lipid profiles has been derived predominantly from studies on Western population. The characteristics and clinical significance of non-fasting lipids in Chinese patients with coronary heart disease (CHD) in response to traditional Chinese diets remain poorly understood. A total of 1022 Chinese CHD patients with coronary artery luminal stenosis 40% as diagnosed by coronary artery angiography were enrolled in the study. All patients received standard treatment for CHD, including statins. They were divided into an intermediate stenosis group (luminal stenosis 40-70%, n = 486) or a severe stenosis group (luminal stenosis 70%, n = 536). Their blood lipid profiles were measured in the fasting state, and 4 hours after normal breakfast. All participants were followed up for five years. Major adverse cardiovascular events (MACE) including all-cause death, cardiac death, myocardial infarction, unscheduled coronary revascularization and stroke were recorded. After normal breakfast intake, patients with intermediate or severe stenosis showed an apparent increase in the levels of triglyceride (TG), remnant cholesterol (RC) and Apo (apolipoprotein) A1 compared to the fasting state, but a significant reduction in the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), Apo B and Apo E. In addition to the traditional risk factors (older age, male, diabetes and smoking) and coronary artery stenosis, the fasting levels of LDL-C and Apo B, as well as non-fasting levels of HDL-C and Apo A1, were identified as independent predictors of 5-year MACE occurrence by multivariate Cox proportional hazards analysis. Patients in the 1st tertile of the non-fasting HDL-C group ( 0.86 mmol/L) showed a significantly higher risk of MACE than 3rd tertile ( 1.07 mmol/L) (1st tertile: 2.786, 95% CI (confidence intervals) [1.808, 4.293], p 0.001). This prospective observational study found that lipid profiles in either the fasting or non-fasting states were associated with the long-term risk of MACE in Chinese CHD patients. In addition to the fasting LDL-C level, a low non-fasting HDL-C level may also be an independent risk factors for cardiovascular events. Measurement of lipid profiles during the non-fasting state may be feasible for the management of CHD patients in routine clinical practice in China.

The accuracy of four formulas for LDL-C calculation at the fasting and postprandial states.

BackgroundElevated level of low-density lipoprotein cholesterol (LDL-C) is concerned as one of the main risk factors for cardiovascular disease, in both the fasting and postprandial states. This study aimed to compare the measured LDL-C with LDL-C calculated by the Friedewald, Martin–Hopkins, Vujovic, and Sampson formulas, and establish which formula could provide the most reliable LDL-C results for Chinese subjects, especially at the postprandial state.MethodsTwenty-six subjects were enrolled in this study. The blood samples were collected from all the subjects before and after taking a daily breakfast. The calculated LDL-C results were compared with LDL-C measured by the vertical auto profile method, at both the fasting and postprandial states. The percentage difference between calculated and measured LDL-C (total error) and the number of results exceeding the total error goal of 12% were established.ResultsThe calculated LDL-CF levels showed no significant difference from LDL-CVAP levels at the fasting state. The calculated LDL-CS were significantly higher than LDL-CVAP at the fasting state (P < 0.05), while the calculated LDL-Cs were very close to LDL-CVAP levels after a daily meal. At the fasting state, the median total error of calculated LDL-CF was 0 (quartile: −3.8 to 6.0), followed by LDL-CS, LDL-CMH, and LDL-CV. At the postprandial states, the median total errors of LDL-CS were the smallest, 1.0 (−7.5, 8.5) and −0.3 (−10.1, 10.9) at 2 and 4 h, respectively. The calculated LDL-CF levels showed the highest correlation to LDL-CVAP and accuracy in evaluating fasting LDL-C levels, while the Sampson formula showed the highest accuracy at the postprandial state.ConclusionThe Friedewald formula was recommended to calculate fasting LDL-C, while the Sampson formula seemed to be a better choice to calculate postprandial LDL-C levels in Chinese subjects.

The Role of Fasting LDL-C Levels in Their Non-fasting Reduction in Patients With Coronary Heart Disease.

The level of low-density lipoprotein cholesterol (LDL-C) decreases to a certain extent after daily meals; however, the influencing factor of this phenomenon has not been fully elucidated. This study included 447 patients with coronary heart disease (CHD). Serum levels of blood lipid parameters at 0, 2, and 4 hours (h) after a daily breakfast were monitored in all subjects. The levels of total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and non-HDL-C significantly decreased, while those of triglycerides (TG) and remnant cholesterol (RC) significantly increased from baseline to 4 h in both male and female patients (P < 0.05). Multiple linear regression analysis showed that fasting LDL-C level, the non-fasting change in RC level at 4 h and fasting TG level were significant predictors of the non-fasting change in LDL-C level at 4 h in patients with CHD, and fasting LDL-C level was the most significantly associated with the non-fasting change in LDL-C level. Patients with lower levels of fasting LDL-C had smaller non-fasting changes in LDL-C levels. When the fasting LDL-C level was <1.4 mmol/L, both absolute reduction and percent reduction in LDL-C level at 4 h were almost zero, which means that the non-fasting LDL-C level at 4 h was approximately equivalent to its fasting value (P < 0.05). This result indicated that the non-fasting changes in LDL-C levels were influenced by fasting LDL-C levels in patients with CHD. When the fasting LDL-C level was <1.4 mmol/L, the non-fasting LDL-C level could replace the fasting value to guide treatment.

A phase I study assessing the safety, tolerability, immunogenicity, and low-density lipoprotein cholesterol-lowering activity of immunotherapeutics targeting PCSK9

PurposeAT04A and AT06A are two AFFITOPE® peptide vaccine candidates being developed for the treatment of hypercholesterolemia by inducing proprotein convertase subtilisin/kexin type 9 (PCSK9)-specific antibodies. This study aimed to investigate safety, tolerability, antibody development, and reduction of low-density lipoprotein cholesterol (LDLc) following four subcutaneous immunizations.MethodsThis phase I, single-blind, randomized, placebo-controlled study was conducted in a total of 72 healthy subjects with a mean fasting LDLc level at baseline of 117.1 mg/dL (range 77–196 mg/dL). Each cohort enrolled 24 subjects to receive three priming immunizations at weeks 0, 4, and 8 and to receive a single booster immunization at week 60 of either AT04A, AT06A, or placebo. In addition to safety (primary objective), the antigenic peptide- and PCSK9-specific antibody response and the impact on LDLc were evaluated over a period of 90 weeks.ResultsThe most common systemic treatment-related adverse events (AEs) reported were fatigue, headache, and myalgia in 75% of subjects in the AT06A group and 58% and 46% of subjects in the placebo and AT04A groups, respectively. Injection site reactions (ISR) representing 63% of all treatment-emergent adverse events (TEAEs), were transient and mostly of mild or moderate intensity and rarely severe (3%). Both active treatments triggered a robust, long-lasting antibody response towards the antigenic peptides used for immunization that optimally cross-reacted with the target epitope on PCSK9. In the AT04A group, a reduction in serum LDLc was observed with a mean peak reduction of 11.2% and 13.3% from baseline compared to placebo at week 20 and 70 respectively, and over the whole study period, the mean LDLc reduction for the AT04A group vs. placebo was −7.2% (95% CI [−10.4 to −3.9], P < 0.0001). In this group, PCSK9 target epitope titers above 50 were associated with clinically relevant LDLc reductions with an individual maximal decrease of 39%.ConclusionsAlthough both AT04A and AT06 were safe and immunogenic, only AT04A demonstrated significant LDLc-lowering activity, justifying further development.Trial registrationEudraCT: 2015-001719-11. ClinicalTrials.govIdentifier: NCT02508896.

Prevalence of high cholesterol levels suggestive of familial hypercholesterolemia in Brazilian adolescents: Data from the study of cardiovascular risk in adolescents

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder with an estimated worldwide prevalence ranging from 1 in 200 individuals to 1 in 500 individuals in its heterozygous form. Individuals with FH exhibit high low-density lipoprotein cholesterol (LDLc) levels from birth, which leads to premature cardiovascular events. In Brazil, like in most countries around the world, FH is considered a public health problem but remains underdiagnosed and undertreated. The aim of this study was to evaluate the prevalence of LDLc or non-high-density lipoprotein cholesterol (non-HDLc) levels suggestive of FH among Brazilian adolescents. The Study of Cardiovascular Risk in Adolescents (ERICA) was a nationwide, school-based, cross-sectional study that assessed the prevalence of cardiovascular risk factors in approximately 75,000 adolescents between 12 and 17years old. Data were analyzed according to sex, age, type of school (public or private), and geographic regions of Brazil. Adolescents with untreated fasting LDLc levels of 160mg/dL or higher or non-HDLc levels of 190mg/dL or higher were suspected to have FH. We also evaluated the prevalence of LDLc levels of 190mg/dL or higher, which is highly suggestive of a diagnosis of FH in this age group. A total of 38,069 adolescents were evaluated; more than half (59.9%) were female and most (74%) attended public schools. The prevalence of LDLc levels of 160mg/dL or higher or non-HDLc levels of 190mg/dL or higher among the adolescents was 0.49% (95% confidence interval: 0.34-0.71; n=209). Moreover, 0.12% of the adolescents (95% confidence interval: 0.04-0.34; n=44) had LDLc levels of 190mg/dL or higher. We estimate that approximately 100,000 (1 in 200) Brazilian adolescents aged 12 to 17years are suspected to have FH on the basis of LDLc and non-HDLc levels. We identified a significant prevalence of cholesterol levels suggestive of FH among Brazilian adolescents. Further evaluation is needed to confirm the diagnoses among the students. Our results reinforce the importance of universal screening as a critical tool for early diagnosis and treatment of FH.

Pharmacologic Prevention of Incident Atrial Fibrillation: Long-Term Results From the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

Although atrial fibrillation (AF) guidelines indicate that pharmacological blockade of the renin-angiotensin system may be considered for primary AF prevention in hypertensive patients, previous studies have yielded conflicting results. We sought to determine whether randomization to lisinopril reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a large clinical trial cohort with extended post-trial surveillance. We performed a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double-blind, active-controlled clinical trial that enrolled hypertensive individuals ≥55 years of age with at least one other cardiovascular risk factor. Participants were randomly assigned to receive amlodipine, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin versus usual care. The primary outcome was the development of either AF or AFL as diagnosed by serial study ECGs or by Medicare claims data. Among 14 837 participants without prevalent AF or AFL, 2514 developed AF/AFL during a mean 7.5±3.2 years of follow-up. Compared with chlorthalidone, randomization to either lisinopril (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15; P=0.46) or amlodipine (hazard ratio, 0.93; 95% confidence interval, 0.84-1.03; P=0.16) was not associated with a significant reduction in incident AF/AFL. Compared with chlorthalidone, treatment with lisinopril is not associated with a meaningful reduction in incident AF or AFL among older adults with a history of hypertension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Efficacy and Safety of Bococizumab (RN316/PF-04950615), a Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, in Hypercholesterolemic Japanese Subjects Receiving a Stable Dose of Atorvastatin or Treatment-Naive - Results From a Randomized, Placebo-Controlled, Dose-Ranging Study.

A Phase 2, dose-ranging study of bococizumab, a monoclonal anti-proprotein convertase subtilisin/kexin type 9 antibody, was conducted in Japanese subjects to assess its efficacy, safety, and tolerability in this population.Methods and Results:Two different hypercholesterolemic study populations were enrolled concurrently: Japanese subjects with uncontrolled low-density lipoprotein cholesterol (LDL-C) despite atorvastatin treatment (LDL-C ≥100 mg/dL; n=121), and Japanese subjects naive to lipid-lowering agents and with LDL-C ≥130 mg/dL (n=97). Subjects within each study population were randomized to bococizumab 50, 100, or 150 mg, or placebo, q14D for 16 weeks; an open-label ezetimibe 10 mg daily arm was also included for the atorvastatin-treated population. Significant, dose-dependent reductions in fasting LDL-C levels were observed in all bococizumab arms of both study populations at Weeks 12 and 16 (adjusted mean percent changes from baseline: 54.1-76.7% for atorvastatin-treated subjects and 47.7-66.8% for treatment-naive subjects; P<0.001 vs. placebo for all). Bococizumab also caused dose-dependent changes in other lipid parameters in both study populations at Weeks 12 and 16. No serious adverse events (AEs) related to bococizumab treatment occurred and all treatment-emergent AEs were mild or moderate in severity. No dose-dependent relationship between bococizumab treatment and development of anti-drug antibodies was observed. Bococizumab was well tolerated and significantly reduced fasting LDL-C in atorvastatin-treated and treatment-naive hypercholesterolemic Japanese subjects. (Clinicaltrials.gov identifier: NCT02055976.).

Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on Conduction System Disease.

Cardiac conduction abnormalities are associated with an increased risk for morbidity and mortality, and understanding factors that accelerate or delay conduction system disease could help to identify preventive and therapeutic strategies. Antifibrotic and anti-inflammatory properties of angiotensin-converting enzyme inhibitors and treatment for hyperlipidemia may reduce the risk for incident conduction system disease. To identify the effect of pharmacologic therapy randomization and clinical risk factors on the incidence of conduction system disease. This secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) investigation acquired data from 623 North American centers. A total of 21 004 ambulatory individuals 55 years or older with hypertension and at least 1 other cardiac risk factor were included in the analysis. Participants were randomly assigned to receive amlodipine besylate, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin sodium vs usual care. An electrocardiogram (ECG) was obtained at study enrollment and every 2 years of follow-up. The development of incident first-degree atrioventricular block, left anterior fascicular block, incomplete left bundle branch block (LBBB), LBBB, incomplete right bundle branch block (RBBB), RBBB, or intraventricular conduction delay was assessed by serial ECGs. The 21 004 participants (11 758 men [56.0%]; 9246 women [44.0%]; mean [SD] age, 66.5 [7.3] years) underwent a mean (SD) follow-up of 5.0 (1.2) years. Among the 1114 participants who developed any conduction defect, 389 developed LBBB, 570 developed RBBB, and 155 developed intraventricular conduction delay. Compared with chlorthalidone, randomization to lisinopril was associated with a significant 19% reduction in conduction abnormalities (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .01). Treatment with amlodipine, however, was not associated with a significant difference in conduction outcome events (HR, 0.94; 95% CI, 0.81-1.09; P = .42). Similarly, pravastatin treatment was not associated with a reduced adjusted risk for incident disease compared with usual hyperlipidemia treatment (HR, 1.13; 95% CI, 0.95-1.35; P = .18). Increased age (HR, 1.47; 95% CI, 1.34-1.63; P < .001), male sex (HR, 0.59; 95% CI, 0.50-0.73; P < .001), white race (HR, 0.59; 95% CI, 0.50-0.70; P < .001), diabetes (HR, 1.23; 95% CI, 1.07-1.42; P = .003), and left ventricular hypertrophy (HR, 3.20; 95% CI, 2.61-3.94; P < .001) were also independently associated with increased risk for conduction system disease. Incident conduction system disease is significantly reduced by lisinopril therapy and is independently associated with multiple clinical factors. Further studies are warranted to determine whether pharmacologic treatment affects conduction abnormality outcomes, including pacemaker implantation. clinicaltrials.gov Identifier: NCT00000542.

Changes in low-density lipoprotein cholesterol levels after discharge for acute myocardial infarction in a real-world patient population.

Aggressively managing low-density lipoprotein cholesterol (LDL-C) after myocardial infarction (MI) is a cornerstone of secondary prevention. The changes in LDL-C after MI and the factors associated with LDL-C levels are unknown. Therefore, we directly measured fasting LDL-C levels in 797 MI patients from 24 US hospitals from 2005 to 2008. Mean LDL-C levels at discharge, 1 month, and 6 months were 95.1, 81.9, and 87.1 mg/dL, respectively. In a hierarchical, multivariable, repeated measures model, older age, male sex, and hypertension were associated with lower LDL-C levels, whereas self-reported avoidance of health care because of cost was associated with higher LDL-C. Both the presence and intensity of statin therapy at discharge were strongly associated with LDL-C levels, with adjusted mean 6-month changes of -3.4 mg/dL (95% confidence interval (CI): -12.1, 5.3) for no statins; 1.7 mg/dL (95% CI: -4.7, 8.1) for low statins; -10.2 mg/dL (95% CI: -14.5, -6.0) for moderate statins; and -13.9 mg/dL (95% CI: -19.7, -8.0) for intensive statins (P < 0.001). In conclusion, we found that greater reductions in LDL-C levels after MI were strongly associated with the presence and intensity of statin therapy, older age, male sex, hypertension, and better socioeconomic status. These findings support the use of intensive statin therapy in post-MI patients and provide estimates of the expected LDL-C changes after MI in a real-world population.

Intravascular ultrasound morphology of culprit lesions and clinical demographics in patients with acute coronary syndrome in relation to low-density lipoprotein cholesterol levels at onset

Despite current standards of care aimed at achieving targets for low-density lipoprotein cholesterol (LDL-C), many patients remain at high residual risk of cardiovascular events. We sought to assess the LDL-C-dependent differences in culprit intravascular ultrasound (IVUS) morphologies and clinical characteristics in patients with acute coronary syndrome (ACS). Eighty-six consecutive ACS patients whose culprit lesions imaged by preintervention IVUS were divided into two groups based on the fasting LDL-C level on admission: a low-LDL-C group (LDL-C <2.6 mmol/l, n = 45) and a high-LDL-C group (LDL-C ≥2.6 mmol/l, n = 41). Patients with stable angina with LDL-C <2.6 mmol/l (n = 30) were also enrolled as an age- and gender-matched control. The low-LDL-C ACS group was significantly older (72 ± 12 vs 64 ± 14 years, P = 0.007) and more diabetic (47 % vs 15 %, P = 0.001). Importantly, IVUS morphologies were comparable between low- and high-LDL-C ACS groups (all P not significant), whereas culprit plaque was more hypoechoic and less calcified in the low-LDL-C ACS group than in the low-LDL-C stable angina group. Furthermore, compared with the low-LDL-C ACS nondiabetic group, the low-LDL-C ACS diabetic group was more obese, more triglyceride rich (1.3 ± 0.6 vs 0.9 ± 0.4 mmol/l, P = 0.003), and more endothelially injured, but no different for the culprit IVUS morphologies. In multivariate analysis, diabetes was independently associated with a low LDL-C level on admission in patients with ACS. There was no relationship between the LDL-C level at onset and culprit-plaque IVUS morphologies in ACS patients, although culprit plaque in the low-LDL-C ACS group was more vulnerable than in the low-LDL-C stable angina group. In patients with low-LDL-C levels, diabetes with atherogenic dyslipidemia might be the key residual risk.

HDL deficiency due to a new insertion mutation (ApoA-INashua) and review of the literature

A 61-year-old white man of European ancestry with significant coronary heart disease since age 42 years and marked high-density lipoprotein (HDL) deficiency (HDL cholesterol 1 mg/dL) was evaluated. His fasting low-density lipoprotein cholesterol level was 42 mg/dL, and his triglycerides were 417 mg/dL on therapy with rosuvastatin 40 mg/day, ezetimibe 10 mg/day, fenofibrate 145 mg/day, and extended-release niacin 2 g/day. Further analysis of his plasma revealed an apolipoprotein (apo) A-I level of 23.5 mg/dL (approximately 20% of normal), and the absence of small alpha-4 HDL, medium alpha-3 HDL, and very large alpha-1 HDL, with only very small pre-beta-1 HDL and large alpha-2 HDL being present. APOA-I gene sequencing revealed a novel heterozygous in-frame insertion mutation with duplication of nucleotides 1535 through 1552 inserted at position 1553, causing a new amino acid glycine at codon 157 and a duplication of amino acids alanine, arginine, alanine, histidine, and leucine at codons 158-162. This novel apoA-I mutation results in the formation of apoA-I that appears to have abnormal lipid binding properties, resulting in impaired reverse cholesterol transport, probable enhanced clearance, and premature coronary heart disease.

The Enhancing Secondary Prevention in Coronary Artery Disease trial

Proven efficacious therapies are sometimes underused in patients with chronic cardiac conditions, resulting in suboptimal outcomes. We evaluated whether evidence summaries, which were either unsigned or signed by local opinion leaders, improved the quality of secondary prevention care delivered by primary care physicians of patients with coronary artery disease. We performed a randomized trial, clustered at the level of the primary care physician, with 3 study arms: control, unsigned statements or opinion leader statements. The statements were faxed to primary care physicians of adults with coronary artery disease at the time of elective cardiac catheterization. The primary outcome was improvement in statin management (initiation or dose increase) 6 months after catheterization. We enrolled 480 adults from 252 practices. Although statin use was high at baseline (n=316 [66%]), most patients were taking a low dose (mean 32% of the guideline-recommended dose), and their low-density lipoprotein (LDL) cholesterol levels were elevated (mean 3.09 mmol/L). Six months after catheterization, statin management had improved in 79 of 157 patients (50%) in the control arm, 85 of 158 (54%) patients in the unsigned statement group (adjusted odds ratio [OR] 1.18, 95% CI 0.71-1.94, p=0.52) and 99 of 165 (60%) patients in the opinion leader statement group (adjusted OR 1.51, 95% CI 0.94-2.42, p=0.09). The mean fasting LDL cholesterol levels after 6 months were similar in all 3 study arms: 2.35 (standard deviation [SD] 0.86) mmol/L in the control arm compared with 2.24 (SD 0.73) among those in the opinion leader group (p=0.48) and 2.19 (SD 0.68) in the unsigned statement group (p=0.32). Faxed evidence reminders for primary care physicians, even when endorsed by local opinion leaders, were insufficient to optimize the quality of care for adults with coronary artery disease. ClinicalTrials.gov trial register no. NCT00175240.

Implications of Changing National Cholesterol Education Program Goals for the Treatment and Control of Hypercholesterolemia

Modifications to the National Cholesterol Education Program (NCEP) guidelines lowered optional low-density lipoprotein cholesterol (LDL-C) treatment goals. We evaluated the implications of widely adopting these optional goals in clinical practice. We performed a cross-sectional study using 1999 to 2002 data from 3,281 U.S. adults aged 20 to 79 years participating the National Health and Nutrition Examination Survey. The primary outcomes were the proportions of adults whose fasting LDL-C levels exceeded NCEP recommended and optional targets from 2001 and 2004. We used survey weights to estimate the size of the U.S. population exceeding targets. We examined outcomes for 4 coronary disease risk subgroups described by the NCEP. Low-density lipoprotein cholesterol values exceeded 2001 NCEP goals for 30.0% of adults, and 35.8% had levels above optional 2004 goals. An estimated 24,900,000 individuals (14.2%) exceeded 2001 thresholds for drug therapy, 46,200,000 (26.3%) exceeded optional 2001 thresholds for drug therapy, and 56,500,000 (32.2%) were above the optional 2004 thresholds for drug therapy. For lower, moderate, moderately high, and high-risk groups, 13.4%, 44.2%, 58.8%, and 71.8%, respectively, exceeded 2001 NCEP goals; 13.4%, 15.7%, 87.4%, and 96.0% of these groups exceeded optional 2004 thresholds for drug therapy. In 1999 to 2002, LDL-C levels commonly exceeded 2001 NCEP goals, especially for moderately high and high-risk individuals, and cholesterol-lowering medications were underused. Optional goals promulgated by the NCEP in 2001 and 2004 moderately increased the number of adults with LDL-C above their goal, and greatly increased the number of low, moderately high, and high-risk adults who exceeded LDL-C thresholds, for cholesterol-lowering medication.

Long-Term Impact of a Community Pharmacist Intervention on Cholesterol Levels in Patients at High Risk for Cardiovascular Events: Extended Follow-up of the Second Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP-plus)

To determine the effect of a community pharmacist intervention in patients at high risk for coronary heart disease on low-density lipoprotein cholesterol (LDL) levels 1 year after completion of the Second Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP- plus ). Patients who completed the original study were invited to make a single return visit to their community pharmacy so that the pharmacist could measure their fasting LDL level using a point-of-care device. The primary outcome was change in LDL level from the 6-month (final) visit to the extended follow-up evaluation. Of the 359 patients who completed the original 6-month visit, data were collected for 162 (45%) patients. The mean +/- SD LDL level at completion of the original study was 107.9 +/- 33.6 mg/dl (2.79 +/- 0.96 mmol/L) (an increase of 2.7 mg/dl [0.07 mmol/L], 95% confidence interval -19.3-7.3 [-0.5-0.19]). Sixty-one (38%) patients were at the target LDL level (< 96.7 mg/dl [< 2.50 mmol/L]). The LDL reduction was maintained 1 year after completion of the extended follow-up. Since most patients were still not at the target LDL level, this finding suggests that continuing intervention is necessary to help patients reach this target.

Self-selected women with polycystic ovary syndrome are reproductively and metabolically abnormal and undertreated

Objective: To determine whether self-selected women with polycystic ovary syndrome (PCOS) are abnormal compared with a control population. Design: Case-control. Setting: Support group meeting organized and initiated by patients. Patient(s): Forty-five self-selected women with PCOS and 80 control women. Intervention(s): Self-selected women with PCOS at a peer support conference completed a questionnaire, had a brief physical, and gave a fasting blood sample. Main Outcome Measure(s): Historical, biometric, and assay results. Result(s): Sixty percent of the women attending the conference participated in the study. Most had been diagnosed with PCOS on the basis of ovarian morphology (35%). They were more likely to be nulliparous and have a history of oligomenorrhea (96%). They were hyperandrogenemic (significantly elevated testosterone and DHEAS levels) compared with control women. Self-selected women with PCOS displayed multiple metabolic abnormalities compared with control women, including elevations in blood pressure, waist-hip ratio, fasting insulin, fasting total cholesterol, and fasting low-density lipoprotein cholesterol levels, as well as a significant decrease in fasting glucose-insulin ratio and high-density lipoprotein cholesterol levels. Conclusion(s): Self-selected women with PCOS have reproductive and metabolic abnormalities. The majority of these women received inadequate treatment despite having risk factors for endometrial cancer, diabetes, and/or heart disease. Our study also suggests that women attending or participating in a PCOS support group are willing and likely to participate in clinical studies.

Attaining United States and European Guideline LDL-cholesterol Levels with Simvastatin in Patients with Coronary Heart Disease (the GOALLS Study)

SummaryThe effectiveness and safety of simvastatin in reducing low-density lipoprotein cholesterol (LDL-C) to target levels in patients with coronary heart disease (CHD) were evaluated in the GOALLS (Getting to Appropriate LDL-C Levels with Simvastatin) study. This multinational, multicentre, prospective, open-label, study consisted of a six-week diet washout period followed by a 14-week titrate-to-goal treatment period with simvastatin. One hundred and ninety-eight men and women with documented CHD and a fasting LDL-C level between 115 mg/dl (3.0 mmol/l) and 180 mg/dl (4.7 mmol/l) and triglycerides (TGs) ≤ 400 mg/dl (4.5 mmol/l) were enrolled. The patients were started on 20 mg simvastatin with dose titration up to 80 mg if the LDL-C remained above 100 mg/dl at weeks 6 and 10. The key efficacy parameters were the percentage of patients achieving US and European LDL-C goals [≤ 100 mg/dl (2.6 mmol/l) and ≤ 115 mg/dl(3.0 mmol/l), respectively]. Safety was evaluated by monitoring laboratory tests and recording adverse events.After 14 weeks of simvastatin (20–80 mg) treatment, approximately 90% of the patients achieved LDL-C goals according to US (87%) and European (94%) guidelines. Most patients (72–93%) achieved target LDL-C levels on 20 mg simvastatin. An estimated 14% of the patients required titration to the 80 mg dose. Treatment with simvastatin (20–80 mg) produced statistically significant improvements in all measured lipid variables by the end of the study. The mean reductions in total cholesterol and LDL-C, and the median reduction in TG, were 28%, 41% and 16%, respectively. The increase in high-density lipoprotein cholesterol and apolipoprotein A-1 were 5% and 4%, respectively. Simvastatin was well tolerated across the dosage range.In conclusion, simvastatin, 20–80 mg/day, was safe and highly effective at reducing LDL-C levels. The recommended US and European LDL-C treatment goals were achieved in approximately 90% of the patients. These goals were similarly achieved for a variety of high-risk sub-groups (hypertensives, diabetics and elderly patients).

Attaining United States and European Guideline LDL-cholesterol Levels with Simvastatin in Patients with Coronary Heart Disease (the GOALLS Study)

SummaryThe effectiveness and safety of simvastatin in reducing low-density lipoprotein cholesterol (LDL-C) to target levels in patients with coronary heart disease (CHD) were evaluated in the GOALLS (Getting to Appropriate LDL-C Levels with Simvastatin) study. This multinational, multicentre, prospective, open-label, study consisted of a six-week diet washout period followed by a 14-week titrate-to-goal treatment period with simvastatin. One hundred and ninety-eight men and women with documented CHD and a fasting LDL-C level between 115 mg/dl (3.0 mmol/l) and 180 mg/dl (4.7 mmol/l) and triglycerides (TGs) ≤ 400 mg/dl (4.5 mmol/l) were enrolled. The patients were started on 20 mg simvastatin with dose titration up to 80 mg if the LDL-C remained above 100 mg/dl at weeks 6 and 10. The key efficacy parameters were the percentage of patients achieving US and European LDL-C goals [≤ 100 mg/dl (2.6 mmol/l) and ≤ 115 mg/dl(3.0 mmol/l), respectively]. Safety was evaluated by monitoring laboratory tests and recording adverse events.After 14 weeks of simvastatin (20–80 mg) treatment, approximately 90% of the patients achieved LDL-C goals according to US (87%) and European (94%) guidelines. Most patients (72–93%) achieved target LDL-C levels on 20 mg simvastatin. An estimated 14% of the patients required titration to the 80 mg dose. Treatment with simvastatin (20–80 mg) produced statistically significant improvements in all measured lipid variables by the end of the study. The mean reductions in total cholesterol and LDL-C, and the median reduction in TG, were 28%, 41% and 16%, respectively. The increase in high-density lipoprotein cholesterol and apolipoprotein A-1 were 5% and 4%, respectively. Simvastatin was well tolerated across the dosage range.In conclusion, simvastatin, 20–80 mg/day, was safe and highly effective at reducing LDL-C levels. The recommended US and European LDL-C treatment goals were achieved in approximately 90% of the patients. These goals were similarly achieved for a variety of high-risk sub-groups (hypertensives, diabetics and elderly patients).

Similar response to simvastatin in patients heterozygous for familial hypercholesterolemia with mRNA negative and mRNA positive mutations

In patients heterozygous for familial hypercholesterolemia, the low-density lipoprotein (LDL) cholesterol lowering effect of β-hydroxy- β-methylglutaryl coenzyme A reductase inhibitors may depend on the nature of the mutation in the LDL receptor gene. To test this hypothesis, we compared the response to simvastatin, 20 mg daily for 9 weeks, between heterozygous carriers of functionally different classes of mutations, i.e. mRNA negative or mRNA positive mutations. Out of 116 consecutive, unrelated patients with familial hypercholesterolemia, 27 patients were selected for molecular analyses: 14 patients with mRNA negative and 13 with mRNA positive mutations. Before simvastatin treatment, patients with mRNA negative mutations had higher levels of LDL cholesterol, lower levels of high-density lipoprotein (HDL) cholesterol and significantly more often tendon xanthomas, compared to patients with mRNA positive mutations. Simvastatin reduced the mean fasting LDL cholesterol levels to a similar percentage in the mRNA negative and mRNA positive patients (37, 36%, respectively, 95% CI of difference −8 to 5%, P=0.2). This effect was similar to the 37% decrease observed in our total series of patients with familial hypercholesterolemia ( n=116). The increase in mean concentration of HDL cholesterol was greater in the mRNA negative group than in the mRNA positive group (16, 0%, respectively, 95% CI of difference 8–25%, P=0.002) independent of the response of total triglycerides to simvastatin. The percentage LDL cholesterol lowering response varied among multiple carriers of the same mutation, even in the case of mRNA negative mutations. We conclude that the percentage LDL lowering response to simvastatin treatment was similar in patients with mRNA negative and mRNA positive mutations. Moreover, variation of this response within multiple carriers of the same mutation suggests an influence of additional factors.