Publications by authors named "Jennifer G Robinson"

252 Publications

Patient perceptions and use of non-statin lipid lowering therapy among patients with or at risk for atherosclerotic cardiovascular disease: Insights from the PALM registry.

Clin Cardiol 2021 Jun 18;44(6):863-870. Epub 2021 May 18.

Duke Clinical Research Institute, Durham, North Carolina, USA.

Background: Non-statin lipid lowering therapies (LLTs) provide additional treatment options for patients. Use patterns and patient perceptions of non-statin LLT remain incompletely described.

Hypothesis: The guideline-recommended statin intensity remains underutilized in patients treated with and without non-statin LLT.

Methods: The PALM Registry collected LLT information on patients with or at risk of ASCVD treated at 125 US clinics in 2015. We compared patient perceptions, lipid levels and statin use among patients treated with and without non-statin LLT.

Results: Among 7720 patients, 1930 (25.0%) were treated with a non-statin LLT (1249 fish oil, 417 fibrates, 329 ezetimibe, 196 niacin). Concurrent statin treatment occurred in 73.7%, of which 45.4% were dosed under the guideline-recommended intensity. Compared with patients on statin alone, patients receiving both a statin and non-statin LLT (n = 1423) were more likely to be male, white race and to perceive themselves as higher risk of ASCVD compared with their peers (38.5% vs. 34.9%, p = .047). Only 27.4% of patients treated with non-statin LLT alone perceived themselves at higher risk. Most (75.7%) patients treated with a non-statin LLT alone reported never being treated with a statin, despite ASCVD in 30.8% of these patients. Among those previously treated with a statin, 59.3% reported being willing to try a statin again.

Conclusions: Non-statin LLT is used in one in four patients with or at risk for ASCVD; its use is frequently in place of statin therapy or in the absence of guideline-recommended statin intensity. More work is needed to establish statins as first line therapy.
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http://dx.doi.org/10.1002/clc.23625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207979PMC
June 2021

Cardiovascular disease (CVD) risk scores, age, or years since menopause to predict cardiovascular disease in the Women's Health Initiative.

Menopause 2021 05 3;28(6):610-618. Epub 2021 May 3.

Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.

Objective: To assess the utility of cardiovascular disease (CVD) risk scores compared to age or years since menopause for prediction of CVD events in the WHI clinical trials.

Methods: Briefly, in the randomized clinical trial 27,347 postmenopausal women age 50 to 79 years entered from 1993 to 1998. Women with a uterus (16,608) were randomized to receive daily oral conjugated equine estrogen (CEE) (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) (5.7 years or placebo), while women with a hysterectomy (10,739) were randomized to receive daily oral CEE (0.625 mg) alone or placebo (7.2 y). CVD risk scores were assessed at baseline and CVD events were adjudicated throughout the follow-up period to the end of the main study phase and to the end of cumulative follow-up. The median follow-up time after the start of the randomized clinical trial to the end of the main study phase was 8.2 years. The median follow-up time to the end of cumulative follow-up was 17.6 years. We compared The American Heart Association/American College of Cardiology (AHA/ACC) and Framingham Heart Study risk scores to age or years since menopause all obtained at baseline to predict subsequent CVD events. The absolute event rates, hazard ratios, and C-statistics (Uno Concordance from Cox proportional models) were compared.

Results: Overall, the hazard ratios for CVD events were highest with calculated CVD scores calculated at trial onset both at the end of the main study (ranging from 2.02 to 10.8 for Q2-Q5, compared to Q1) and at cumulative follow-up (ranging from 1.76 to 8.86 for Q2-Q5, compared to Q1). While older age and years since menopause at baseline were also associated with higher CVD event rates, better risk prediction was accomplished by using CVD risk scores. The Framingham Heart Study BMI score had the highest C-statistic at the end of the main study (0.711) and after 17.6 years through the end of follow-up (0.689).

Conclusions: CVD risk scores can help identify postmenopausal women at higher risk for CVD beyond age or time since menopause. Risk scoring that better estimates vascular aging may facilitate CVD risk prevention. When performed prior to initiation of menopausal hormone therapy, scores can better inform HT risk/benefit discussions.
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http://dx.doi.org/10.1097/GME.0000000000001753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141005PMC
May 2021

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

Nat Commun 2021 04 22;12(1):2329. Epub 2021 Apr 22.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
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http://dx.doi.org/10.1038/s41467-021-22370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062567PMC
April 2021

Effects of menopausal hormone therapy on erythrocyte n-3 and n-6 PUFA concentrations in the Women's Health Initiative randomized trial.

Am J Clin Nutr 2021 06;113(6):1700-1706

Department of Epidemiology, College of Public Health, Iowa City, IA, USA.

Background: The factors other than dietary intake that determine tissue concentrations of EPA and DHA remain obscure. Prior studies suggested that, in women, endogenous estrogen may accelerate synthesis of DHA from ɑ-linolenic acid (ALA), but the effects of exogenous estrogen on RBC n-3 (ɷ-3) PUFA concentrations are unknown.

Objective: We tested the hypothesis that menopausal hormone therapy (HT) would increase RBC n-3 PUFA concentrations.

Methods: Postmenopausal women (ages 50-79 y) were assigned to HT or placebo in the Women's Health Initiative (WHI) randomized trial. The present analyses included a subset of 1170 women (ages 65-79 y) who had RBC PUFA concentrations measured at baseline and at 1 y as participants in the WHI Memory Study. HT included conjugated equine estrogens (E) alone for women without a uterus (n = 560) and E plus medroxyprogesterone acetate (P) for those with an intact uterus (n = 610). RBC n-3 and n-6 (ɷ-6) PUFAs were quantified.

Results: Effects of E alone and E+P on PUFA profiles were similar and were thus combined in the analyses. Relative to the changes in the placebo group after 1 y of HT, docosapentaenoic acid (DPA; n-3) concentrations decreased by 10% (95% CI: 7.3%, 12.5%), whereas DHA increased by 11% (95% CI: 7.4%, 13.9%) in the HT group. Like DHA, DPA n-6 increased by 13% from baseline (95% CI: 10.0%, 20.3%), whereas linoleic acid decreased by 2.0% (95% CI: 1.0%, 4.1%; P values at least <0.01 for all). EPA and arachidonic acid concentrations were unchanged.

Conclusions: HT increased RBC concentrations of the terminal n-3 and n-6 PUFAs (DHA and DPA n-6). These findings are consistent with an estrogen-induced increase in DHA and DPA n-6 synthesis, which is consistent with an upregulation of fatty acid elongases and/or desaturases in the PUFA synthetic pathway. The clinical implications of these changes require further study. The Women's Health Initiative Memory Study is registered at clinicaltrials.gov as NCT00685009. Note that the data presented here were not planned as part of the original trial, and therefore are to be considered exploratory.
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http://dx.doi.org/10.1093/ajcn/nqaa443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168349PMC
June 2021

n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies.

Diabetes Care 2021 May 3;44(5):1133-1142. Epub 2021 Mar 3.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.

Research Design And Methods: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.

Results: A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses.

Conclusions: Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.
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http://dx.doi.org/10.2337/dc20-2426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132316PMC
May 2021

Patient-Perceived Versus Actual Risk of Cardiovascular Disease and Associated Willingness to Consider and Use Prevention Therapy.

Circ Cardiovasc Qual Outcomes 2021 01 13;14(1):e006548. Epub 2021 Jan 13.

Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., T.Y.W., S.L., X.M., Z.L., E.D.P.).

Background: Cardiovascular prevention guidelines use estimated 10-year atherosclerotic cardiovascular disease (CVD) risk based on the pooled cohort equations to guide treatment decisions and engage patients in shared decision-making. We sought to determine patient perceived versus actual risk of atherosclerotic CVD and associations with willingness for preventive therapy.

Methods: We evaluated calculated and perceived CVD risk among 4187 patients across 124 sites in the Patient and Provider Assessment of Lipid Management Registry. Ten-year risk was assessed using the pooled cohort equations; risk relative-to-peers was determined based on age-, sex-, and race-based percentiles; and patient estimates of risk were assessed using patient surveys. Poisson regression models evaluated associations between risk estimates, statin use, and willingness to take prevention therapy.

Results: Overall, there was no correlation between patients' estimates of their 10-year CVD risk and calculated 10-year risk (ρ=-0.01, =0.46), regardless of age, sex, race, or socioeconomic status. The majority (72.2%) overestimated their 10-year CVD risk relative to the pooled cohorts equation (mean perceived 33.3% versus mean calculated 17.1%, <0.01). Patients' perceptions of their risk relative-to-peers were slightly correlated with standardized risk percentiles (ρ=0.19, <0.01), although most had overly optimistic views of how risk compared with their peers. Increasing perceived risk was not associated with current statin use (=0.18) but was associated with willingness to consider future prevention therapy (<0.01). Perceived risk relative-to-peers was associated with increased prevalent statin use (risk ratio 1.04 per category increase [95% CI, 1.02-1.06]) and reported willingness for prevention therapy (risk ratio 1.11 [95% CI, 1.07-1.16]).

Conclusions: When asked, most patients overestimate their 10-year risk but hold an optimistic bias of their risk relative to age-, race-, and sex-matched peers. Providing accurate absolute risk assessments to patients without proper context may paradoxically decrease many patients' perceived risk of CVD, thereby disincentivizing initiation of CVD risk reduction therapy.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.006548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855929PMC
January 2021

The neuropsychology of statin intolerance.

Nat Rev Cardiol 2021 Mar;18(3):153-154

Departments of Epidemiology and Internal Medicine, Division of Cardiology, University of Iowa, Iowa City, IA, USA.

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http://dx.doi.org/10.1038/s41569-020-00502-3DOI Listing
March 2021

Clinical implications of the log linear association between LDL-C lowering and cardiovascular risk reduction: Greatest benefits when LDL-C >100 mg/dl.

PLoS One 2020 29;15(10):e0240166. Epub 2020 Oct 29.

Bluhm Cardiovascular Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.

Background: The log linear association between on-treatment LDL-C levels and ASCVD events is amplified in higher risk patient subgroups of statin versus placebo trials.

Objectives: Update previous systematic review to evaluate how the log linear association influences the magnitude of cardiovascular risk reduction from intensifying LDL-C lowering therapy.

Methods: MEDLINE/PubMED, Clinical trials.gov, and author files were searched from 1/1/2005 through 10/30/2019 for subgroup analyses of cardiovascular outcomes trials of moderate versus high intensity statin, ezetimibe, and PCSK9 mAbs with an ASCVD endpoint (nonfatal myocardial infarction or stroke, cardiovascular death). Annualized ASCVD event rates were used to extrapolate 5-year ASCVD risk for each treatment group reported in subgroup analyses, which were grouped into a priori risk groups according to annualized placebo/control rates of ≥4%, 3-3.9%, or <3% ASCVD risk. Data were pooled using a random-effects model. Weighted least-squares regression was used to fit linear and log-linear models.

Results: Systematic review identified 96 treatment subgroups from 2 trials of moderate versus high intensity statin, 2 trials of a PCSK9 mAb versus placebo, and 1 trial of ezetimibe versus placebo. A log linear association between on-treatment LDL-C and ASCVD risk represents the association between on-treatment LDL-C levels and ASCVD event rates, especially in higher risk subgroups. Greater relative and absolute cardiovascular risk reductions from LDL-C lowering were observed when baseline LDL-C was >100 mg/dl and in extremely high risk ASCVD patient groups.

Conclusions: Greater cardiovascular and mortality risk reduction benefits from intensifying LDL-C lowering therapy may be expected in those with LDL-C ≥100 mg/dl, or in extremely high risk patient groups. When baseline LDL-C <100 mg/dl, the log linear association between LDL-C and event rates suggests that treatment options other than further LDL-C lowering should also be considered for optimal risk reduction.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240166PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595281PMC
December 2020

Challenges and Opportunities for the Prevention and Treatment of Cardiovascular Disease Among Young Adults: Report From a National Heart, Lung, and Blood Institute Working Group.

J Am Heart Assoc 2020 10 30;9(19):e016115. Epub 2020 Sep 30.

Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago IL.

Improvements in cardiovascular disease (CVD) rates among young adults in the past 2 decades have been offset by increasing racial/ethnic and gender disparities, persistence of unhealthy lifestyle habits, overweight and obesity, and other CVD risk factors. To enhance the promotion of cardiovascular health among young adults 18 to 39 years old, the medical and broader public health community must understand the biological, interpersonal, and behavioral features of this life stage. Therefore, the National Heart, Lung, and Blood Institute, with support from the Office of Behavioral and Social Science Research, convened a 2-day workshop in Bethesda, Maryland, in September 2017 to identify research challenges and opportunities related to the cardiovascular health of young adults. The current generation of young adults live in an environment undergoing substantial economic, social, and technological transformations, differentiating them from prior research cohorts of young adults. Although the accumulation of clinical and behavioral risk factors for CVD begins early in life, and research suggests early risk is an important determinant of future events, few trials have studied prevention and treatment of CVD in participants <40 years old. Building an evidence base for CVD prevention in this population will require the engagement of young adults, who are often disconnected from the healthcare system and may not prioritize long-term health. These changes demand a repositioning of existing evidence-based treatments to accommodate new sociotechnical contexts. In this article, the authors review the recent literature and current research opportunities to advance the cardiovascular health of today's young adults.
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http://dx.doi.org/10.1161/JAHA.120.016115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792379PMC
October 2020

Pharmacodynamic relationship between PCSK9, alirocumab, and LDL-C lowering in the ODYSSEY CHOICE I trial.

J Clin Lipidol 2020 Sep - Oct;14(5):707-719. Epub 2020 Jul 25.

University of Iowa, Iowa City, IA, USA.

Background: The ODYSSEY CHOICE I study (NCT01926782) evaluated alirocumab 300 mg every 4 weeks (Q4W) in patients with hypercholesterolemia receiving maximally tolerated statin or no statin.

Objective: The objective of the study was to assess the relationship between alirocumab, proprotein convertase subtilisin/kexin type 9 (PCSK9), and low-density lipoprotein cholesterol (LDL-C) concentrations with the CHOICE I alirocumab dosing regimen.

Methods: This analysis included 803 patients (547 statin-treated, 256 without statin) who were randomized to alirocumab 300 mg Q4W, alirocumab 75 mg every 2 weeks (Q2W), or placebo. 300 mg Q4W and 75 mg Q2W doses were adjusted to 150 mg Q2W at Week 12 if Week 8 LDL-C was >70 or >100 mg/dL, depending on cardiovascular risk, or if LDL-C reduction was <30% from baseline.

Results: Most patients remained on 300 mg Q4W without dose adjustment as they achieved study-defined LDL-C goals at Week 8 (statin-treated: 80.7%; no statin: 85.3%). LDL-C was reduced by 60.5%-71.9% over Weeks 20-24 in patients on 300 mg Q4W and 57.2%-63.0% in patients with dose adjustment from 300 mg Q4W to 150 mg Q2W. Statin-treated patients had higher cardiovascular risk as well as higher free PCSK9 and lower alirocumab concentrations (vs no statin), suggesting increased target-mediated clearance. Regardless of statin status, the most common adverse events in alirocumab-treated patients were injection-site reaction and headache.

Conclusions: Data provide further insight on alirocumab's mode of action in terms of relationship between alirocumab, PCSK9, and LDL-C, and disease severity, and support the use of alirocumab 300 mg Q4W as an efficacious dosing regimen for clinically meaningful LDL-C reductions.
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http://dx.doi.org/10.1016/j.jacl.2020.07.009DOI Listing
July 2020

A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies.

Cardiol Ther 2020 Dec 20;9(2):447-465. Epub 2020 Jun 20.

Academic Medical Center of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam-Zuidoost, Amsterdam, The Netherlands.

Introduction: Clinicians, payers, guideline committees, and policymakers support the use of high-intensity statins in patients at high risk for complications of cardiovascular disease (CVD). Guidelines and recommendations provide guidance on next steps for patients with inadequate low-density lipoprotein cholesterol (LDL-C) control on maximally tolerated statin or for those who are statin-intolerant. Ezetimibe and evolocumab improve CV outcomes when added to statins in high-CV-risk populations. The aim of the study was to compare evolocumab and ezetimibe for lipid-lowering efficacy and safety.

Methods: We summarized data from 1427 patients from three phase 3 evolocumab studies comparing double-blinded evolocumab vs. ezetimibe. These studies evaluated four distinct populations: those free of CVD receiving each agent as monotherapy, patients with CVD receiving add-on therapy to low- or high-intensity statin, and statin-intolerant patients. Lipid efficacy and safety were reported at week 12.

Results: Across the studies, evolocumab reduced LDL-C by a mean 55-61% from baseline to week 12; ezetimibe lowered LDL-C by 18-20% from baseline (mean difference = 38-43% favoring evolocumab; p < 0.0001). This corresponded to absolute reductions in LDL-C of 60-104 mg/dL with evolocumab vs. 17-35 mg/dL with ezetimibe. Evolocumab also significantly improved other lipids and led to a higher percentage of patients achieving LDL-C goals vs. ezetimibe. Adverse events and discontinuation rates (oral and parenteral therapy) were balanced across groups, suggesting good tolerance and acceptance of both treatments.

Conclusions: Evolocumab outperformed ezetimibe in efficacy and lipid goal attainment. Both products demonstrated good safety/tolerability. These data may help guide access decisions for high-risk patients with inadequate treatment response or intolerance to statin therapy.
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http://dx.doi.org/10.1007/s40119-020-00181-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584715PMC
December 2020

Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.

PLoS Med 2020 06 12;17(6):e1003102. Epub 2020 Jun 12.

MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.

Background: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D).

Methods And Findings: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970-1973 to 2006-2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3-75.5 years; % women = 20.4%-62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41-1.66; p < 0.001) for 16:0, 1.40 (1.33-1.48; p < 0.001) for 16:1n-7, 1.14 (1.05-1.22; p = 0.001) for 18:0, and 1.16 (1.07-1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%-73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94-1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors.

Conclusions: Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.
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http://dx.doi.org/10.1371/journal.pmed.1003102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292352PMC
June 2020

Beliefs, risk perceptions, and lipid management among patients with and without diabetes: Results from the PALM registry.

Am Heart J 2020 07 30;225:88-96. Epub 2020 Apr 30.

Duke Clinical Research Institute, Durham, NC; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC.

Intensive lipid management is critical to reduce cardiovascular (CV) risk for patients with diabetes mellitus (DM).

Methods: We performed an observational study of 7628 patients with (n = 2943) and without DM (n = 4685), enrolled in the Provider Assessment of Lipid Management (PALM) registry and treated at 140 outpatient clinics across the United States in 2015. Patient self-estimated CV risk, patient-perceived statin benefit and risk, observed statin therapy use and dosing were assessed.

Results: Patients with DM were more likely to believe that their CV risk was elevated compared with patients without DM (39.1% vs 29.3%, P < .001). Patients with DM were more likely to receive a statin (74.2% vs 63.5%, P < .001) but less likely to be treated with guideline-recommended statin intensity (36.5% vs 46.9%, P < .001), driven by the low proportion (16.5%) of high risk (ASCVD risk ≥7.5%) primary prevention DM patients treated with a high intensity statin. Patients with DM treated with guideline-recommended statin intensity were more likely to believe they were at high CV risk (44.9% vs 38.4%, P = .005) and that statins can reduce this risk (41.1% vs 35.6%, P = .02), compared with patients treated with lower than guideline-recommended statin intensity. Compared with patients with an elevated HgbA1c, patients with well-controlled DM were no more likely to be on a statin (77.9% vs 79.3%, P = .43).

Conclusions: In this nationwide study, the majority of patients with DM were treated with lower than guideline-recommended statin intensity. Patient education and engagement may help providers improve lipid therapy for these high-risk patients.
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http://dx.doi.org/10.1016/j.ahj.2020.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539544PMC
July 2020

A Population-Based Study of Simvastatin Drug-Drug Interactions in Cardiovascular Disease Patients.

AMIA Jt Summits Transl Sci Proc 2020 30;2020:664-673. Epub 2020 May 30.

Institute for Health Informatics, University of Minnesota, Minneapolis, MN, USA.

Simvastatin is a commonly used medication for lipid management and cardiovascular disease, however, the risk of adverse events (AEs) with its use increases via drug-drug interaction (DDI) exposures. Patients were extracted if initially diagnosed with cardiovascular disease and newly initiated simvastatin therapy. The cohort was divided into a DDI-exposed group and a non-DDI exposed group. The DDI-exposed group was further divided into gemfibrozil, clarithromycin, and erythromycin exposure groups. The outcome was defined as a composite of predefined AEs. Our results show that the simvastatin-DDI group had a higher illness burden with longer simvastatin exposure time and more medical care follow-up compared with the simvastatin-non-DDI exposed group. AEs occurred more frequently in subjects exposed to interacting drugs with a higher risk for clarithromycin and erythromycin exposed subjects than for gemfibrozil subjects.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233072PMC
May 2020

Low LDL-C Levels: Likely No Short-Term Cognitive Harm.

J Am Coll Cardiol 2020 05;75(18):2294-2296

Departments of Epidemiology and Internal Medicine, Division of Cardiology, University of Iowa, Iowa City, Iowa. Electronic address:

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http://dx.doi.org/10.1016/j.jacc.2020.03.040DOI Listing
May 2020

Early pregnancy prediction of gestational diabetes mellitus risk using prenatal screening biomarkers in nulliparous women.

Diabetes Res Clin Pract 2020 May 6;163:108139. Epub 2020 Apr 6.

Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, United States; Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, United States. Electronic address:

Aims: To evaluate the clinical utility of first and second trimester prenatal screening biomarkers for early pregnancy prediction of gestational diabetes mellitus (GDM) risk in nulliparous women.

Methods: We conducted a population-based cohort study of nulliparous women participating in the California Prenatal Screening Program from 2009 to 2011 (n = 105,379). GDM was ascertained from hospital discharge records or birth certificates. Models including maternal characteristics and prenatal screening biomarkers were developed and validated. Risk stratification and reclassification were performed to assess clinical utility of the biomarkers.

Results: Decreased levels of first trimester pregnancy-associated plasma protein A (PAPP-A) and increased levels of second trimester unconjugated estriol (uE) and dimeric inhibin A (INH) were associated with GDM. The addition of PAPP-A only and PAPP-A, uE, and INH to maternal characteristics resulted in small, yet significant, increases in area under the receiver operating characteristic curve (AUC) (maternal characteristics only: AUC 0.714 (95% CI 0.703-0.724), maternal characteristics + PAPP-A: AUC 0.718 (95% CI 0.707-0.728), maternal characteristics + PAPP-A, uE, and INH: AUC 0.722 (0.712-0.733)); however, no net improvement in classification was observed.

Conclusions: PAPP-A, uE, and INH have limited clinical utility for prediction of GDM risk in nulliparous women. Utility of other readily accessible clinical biomarkers in predicting GDM risk warrants further investigation.
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http://dx.doi.org/10.1016/j.diabres.2020.108139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269799PMC
May 2020

The next treatment paradigm in cardiovascular prevention?

Lancet 2019 12 3;394(10215):2129-2131. Epub 2019 Dec 3.

Departments of Epidemiology and Internal Medicine, Division of Cardiology, University of Iowa, Iowa City, IA 52242, USA. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(19)32949-6DOI Listing
December 2019

Lipid update 2020 - Introduction and foreword.

Prog Cardiovasc Dis 2019 Sep - Oct;62(5):373-374. Epub 2019 Nov 9.

Departments of Epidemiology and Internal Medicine, Division of Cardiology, University of Iowa, United States of America. Electronic address:

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http://dx.doi.org/10.1016/j.pcad.2019.11.006DOI Listing
January 2020

Relationship between alirocumab, PCSK9, and LDL-C levels in four phase 3 ODYSSEY trials using 75 and 150 mg doses.

J Clin Lipidol 2019 Nov - Dec;13(6):979-988.e10. Epub 2019 Oct 14.

Harvard Clinical Research Institute, Boston, MA, USA.

Background: Alirocumab is a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9).

Objective: Changes in PCSK9, alirocumab, and low-density lipoprotein cholesterol (LDL-C) levels were assessed after treatment with alirocumab at doses of 75 or 150 mg every 2 weeks (Q2W).

Methods: Data were analyzed from 4 phase 3 trials (MONO; COMBO II; FH I; LONG TERM); all but MONO enrolled patients on statins. Three trials evaluated alirocumab 75 mg Q2W, with possible dose increase to 150 mg Q2W at week 12 based on week 8 LDL-C; LONG TERM studied alirocumab 150 mg Q2W.

Results: Patients on background statin therapy had higher mean baseline free PCSK9 concentrations vs patients not on statin. After alirocumab administration, increased alirocumab concentrations were associated with dramatic reductions in circulating free PCSK9, resulting in significant LDL-C reductions and a corresponding increase in inactive PCSK9:alirocumab complex. Alirocumab dose increase was associated with a further lowering of PCSK9 and LDL-C. Patients with higher baseline LDL-C levels (>160 mg/dL) were more likely to have their dose increased. LDL-C reductions with alirocumab were consistent between patients with baseline PCSK9 levels above or below the median when the dose increase strategy was used. When started as alirocumab 150 mg Q2W, patients with PCSK9 levels above vs below the median had a greater LDL-C reduction.

Conclusions: Alirocumab-induced changes in PCSK9 and LDL-C levels were consistent with the known physiologic relationship between PCSK9, LDL receptor, and LDL-C levels, as well as statin-induced increases in PCSK9 production.
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http://dx.doi.org/10.1016/j.jacl.2019.10.004DOI Listing
July 2020

New insights into managing symptoms during statin therapy.

Prog Cardiovasc Dis 2019 Sep - Oct;62(5):390-394. Epub 2019 Oct 26.

Departments of Epidemiology and Internal Medicine, Division of Cardiology, University of Iowa, United States of America. Electronic address:

Symptoms during statin therapy are common and often attributed to statin intolerance. Recent data suggest few patients are truly intolerant to statins. Muscle symptoms are similar in statin and control groups in blinded treatment periods of clinical trials. The "nocebo" effect may occur during open-label statin treatment, when previously asymptomatic study participants report symptoms attributed to statin therapy, or during placebo-controlled trials. Most patients reporting statin intolerance can tolerate blinded moderate intensity statin therapy. In clinical practice the large majority of patients are willing to retry a statin, and of those who do, >80-90% successfully remain on statin therapy long-term. Emerging evidence from brain imaging studies and contemporary approaches to pain management suggests that building trust and managing patient expectations can minimize the "nocebo" effect in statin-treated patients.
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http://dx.doi.org/10.1016/j.pcad.2019.10.005DOI Listing
January 2020

Lipid management beyond the guidelines.

Prog Cardiovasc Dis 2019 Sep - Oct;62(5):384-389. Epub 2019 Oct 25.

Departments of Epidemiology and Internal Medicine, Division of Cardiology, University of Iowa. Electronic address:

The 2018 AHA/ACC cholesterol guideline builds on the 2013 ACC/AHA cholesterol guideline statin recommendations to provide more detailed recommendations for the use of nonstatin therapy risk stratification for primary prevention statin use. New information has become available after the development of the 2018 AHA/ACC cholesterol guideline that can further inform clinical practice. Proprotein convertase subtilisin kexin type-9 (PCSK9) monoclonal antibodies are now a reasonable or even good value following over 60% reductions in their acquisition price, and the identification of high risk patient groups most likely to benefit from further low-density lipoprotein cholesterol (LDL-C) lowering. Meta-analyses and clinical trial data now show that patients with LDL-C ≥ 100 mg/dl are more likely to experience progressively greater reductions in the risk of cardiovascular and total mortality and coronary heart disease events for progressively higher LDL-C levels. Icosapent ethyl, a highly concentrated form of modified EPA has been shown to reduce cardiovascular events in high risk patients with moderate hypertriglyceridemia on statin therapy. Comparisons with other statin guidelines revealed that statin initiation for those with ≥7.5% 10-year atherosclerotic cardiovascular disease (ASCVD) risk is the most effective strategy for reducing the most ASCVD events for the proportion of the population treated. Data from younger populations finally became available for coronary artery calcium (CAC) scoring (mean age of 51 years) which confirmed the value of CAC > 0 for identifying individuals at increased ASCVD risk most likely to benefit from statin initiation. This analysis also found that statins could keep CAC = 0 in those with risk factors. Epidemiologic pooling studies now clearly show that LDL-C and non-high-density lipoprotein cholesterol levels in young adulthood confer excess risk for ASCVD later in life. Accumulating data support earlier risk factor intervention trials as the next research priority.
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http://dx.doi.org/10.1016/j.pcad.2019.10.004DOI Listing
January 2020

Can atherosclerosis be cured?

Curr Opin Lipidol 2019 12;30(6):477-484

Departments of Epidemiology & Medicine, Prevention Intervention Center, Iowa City, Iowa, USA.

Purpose Of Review: Determine if evidence supports interventions to prevent development of atherosclerosis and atherosclerotic cardiovascular disease (ASCVD) events and death.

Recent Findings: An extensive body of evidence supports the fundamental causal role of apolipoprotein B lipoproteins in the development of atherosclerosis. Recent epidemiologic studies have shown that LDL-cholesterol (LDL-C) and non-HDL-cholesterol levels in early adults are associated with accelerated subclinical atherosclerosis and an excess of atherosclerotic cardiovascular events later in life. Animal and human data have shown that intensive LDL-C lowering can regress earlier stages of atherosclerosis.

Summary: The next research priority is evaluating the impact of lowering LDL-C earlier in life to regress early atherosclerosis, followed by trials to demonstrate this approach will eradicate later-life ASCVD events and death. This approach of curing atherosclerosis will likely be the most effective strategy for reducing the huge global burden of atherosclerosis.
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http://dx.doi.org/10.1097/MOL.0000000000000644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375463PMC
December 2019

Genetic Risk Scores for Maternal Lipid Levels and Their Association with Preterm Birth.

Lipids 2019 10 29;54(10):641-650. Epub 2019 Aug 29.

Department of Epidemiology, University of Iowa, 145 N. Riverside Drive, Iowa City, IA, 52242-3535, USA.

Maternal lipid profiles are associated with risk for preterm birth (PTB), although the lipid component and effect size are inconsistent between studies. It is also unclear whether these associations are the result of excessive changes in lipid metabolism during pregnancy or genetic variability in genes controlling basal lipid metabolism. This study investigates the association between genetic risk scores (GRS) for four lipid components (high-density lipoprotein [HDL-C], low-density lipoprotein [LDL-C], triacylglycerols [TAG], and total cholesterol [TC]) with risk for PTB. Subjects included 954 pregnant women from California for whom second trimester serum samples were available, of which 479 gave birth preterm and 475 gave birth at term. We genotyped 96 single-nucleotide polymorphisms, which were selected from genome-wide association studies of lipid levels in adult populations. Lipid-specific GRS were constructed for HDL-C, LDL-C, TAG, and TC. The associations between GRS and PTB were analyzed using logistic regression. A higher HDL-C GRS was associated with increased risk for PTB overall and spontaneous PTB. Higher TAG and TC GRS were associated with decreased risk for PTB overall and spontaneous PTB. This study identifies counter-intuitive associations between lipid GRS and spontaneous PTB. Further replication studies are needed to confirm these findings, but they suggest that our current scientific understanding of the relationship between lipid metabolism, PTB, and genetics is incomplete.
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http://dx.doi.org/10.1002/lipd.12186DOI Listing
October 2019

Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association.

Circulation 2019 09 19;140(12):e673-e691. Epub 2019 Aug 19.

Hypertriglyceridemia (triglycerides 200-499 mg/dL) is relatively common in the United States, whereas more severe triglyceride elevations (very high triglycerides, ≥500 mg/dL) are far less frequently observed. Both are becoming increasingly prevalent in the United States and elsewhere, likely driven in large part by growing rates of obesity and diabetes mellitus. In a 2002 American Heart Association scientific statement, the omega-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were recommended (at a dose of 2-4 g/d) for reducing triglycerides in patients with elevated triglycerides. Since 2002, prescription agents containing EPA+DHA or EPA alone have been approved by the US Food and Drug Administration for treating very high triglycerides; these agents are also widely used for hypertriglyceridemia. The purpose of this advisory is to summarize the lipid and lipoprotein effects resulting from pharmacological doses of n-3 FAs (>3 g/d total EPA+DHA) on the basis of new scientific data and availability of n-3 FA agents. In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides. When used to treat hypertriglyceridemia, n-3 FAs with EPA+DHA or with EPA-only appear roughly comparable for triglyceride lowering and do not increase low-density lipoprotein cholesterol when used as monotherapy or in combination with a statin. In the largest trials of 4 g/d prescription n-3 FA, non-high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins. The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin. The results of a trial of 4 g/d prescription EPA+DHA in hypertriglyceridemia are anticipated in 2020. We conclude that prescription n-3 FAs (EPA+DHA or EPA-only) at a dose of 4 g/d (>3 g/d total EPA+DHA) are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents.
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http://dx.doi.org/10.1161/CIR.0000000000000709DOI Listing
September 2019

Sex Differences in the Use of Statins in Community Practice.

Circ Cardiovasc Qual Outcomes 2019 08 16;12(8):e005562. Epub 2019 Aug 16.

Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (M.G.N., T.Y.W., Q.X., Z.L., E.D.P., A.M.N.).

Background: Female patients have historically received less aggressive lipid management than male patients. Contemporary care patterns and the potential causes for these differences are unknown.

Methods And Results: Examining the Patient and Provider Assessment of Lipid Management Registry-a nationwide registry of outpatients with or at risk for atherosclerotic cardiovascular disease-we compared the use of statin therapy, guideline-recommended statin dosing, and reasons for undertreatment. We specifically analyzed sex differences in statin treatment and guideline-recommended statin dosing using multivariable logistic regression. Among 5693 participants (43% women) eligible for 2013 American College of Cardiology/American Heart Association Cholesterol Guideline-recommended statin treatment, women were less likely than men to be prescribed any statin therapy (67.0% versus 78.4%; P<0.001) or to receive a statin at the guideline-recommended intensity (36.7% versus 45.2%; P<0.001). Women were more likely to report having previously never been offered statin therapy (18.6% versus 13.5%; P<0.001), declined statin therapy (3.6% versus 2.0%; P<0.001), or discontinued their statin (10.9% versus 6.1%; P<0.001). Women were also less likely than men to believe statins were safe (47.9% versus 55.2%; P<0.001) or effective (68.0% versus 73.2%; P<0.001) and more likely to report discontinuing their statin because of a side effect (7.9% versus 3.6%; P<0.001). Sex differences in both overall and guideline-recommended intensity statin use persisted after adjustment for demographics, socioeconomic factors, clinical characteristics, patient beliefs, and provider characteristics (adjusted odds ratio, 0.70; 95% CI, 0.61-0.81; P<0.001; and odds ratio, 0.82; 95% CI, 0.73-0.92; P<0.01, respectively). Sex differences were consistent across primary and secondary prevention indications for statin treatment.

Conclusions: Women eligible for statin therapy were less likely than men to be treated with any statin or guideline-recommended statin intensity. A combination of women being offered statin therapy less frequently, while declining and discontinuing treatment more frequently, accounted for these sex differences in statin use.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.118.005562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903404PMC
August 2019

Treatment effect of alirocumab according to age group, smoking status, and hypertension: Pooled analysis from 10 randomized ODYSSEY studies.

J Clin Lipidol 2019 Sep - Oct;13(5):735-743. Epub 2019 Jun 29.

University of Iowa, Iowa City, IA, USA.

Background: Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease.

Objective: We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status.

Methods: Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24-104 weeks' duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non-familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75 mg every 2 weeks (Q2W) to 150 mg Q2W at Week 12 if predefined risk-based LDL-C goals were not achieved at Week 8 (≥70 mg/dL in very high cardiovascular risk; ≥100 mg/dL in moderate or high cardiovascular risk). Two trials compared alirocumab 150 mg Q2W vs placebo. The efficacy and safety of alirocumab were assessed post hoc in subgroups stratified by age (<65, ≥65 to <75, ≥75 years) and baseline hypertension or smoking status.

Results: Alirocumab reduced LDL-C by 23.7% (75/150 mg vs ezetimibe + statin) to 65.4% (150 mg vs placebo + statin) from baseline to Week 24 vs control. Subgroup analyses confirmed no significant interactions in response to alirocumab between age group, hypertension, or smoking status. Overall rates of treatment-emergent adverse events were similar between alirocumab and control groups.

Conclusions: In this pooled analysis from 10 trials, alirocumab led to substantial LDL-C reductions vs control in every age group and regardless of hypertension or smoking status. Alirocumab was well tolerated in all subgroups.
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http://dx.doi.org/10.1016/j.jacl.2019.06.006DOI Listing
July 2020

Enhancing the value of PCSK9 monoclonal antibodies by identifying patients most likely to benefit. A consensus statement from the National Lipid Association.

J Clin Lipidol 2019 Jul - Aug;13(4):525-537. Epub 2019 May 16.

Department of Internal Medicine, University of Pennsylvania Health System, Philadelphia, PA, USA.

Acquisition costs and cost-effectiveness have limited access and recommendations to use proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibiting monoclonal antibodies (mAbs). Recently, prices were reduced by 60% for alirocumab and evolocumab. This statement systematically reviewed subgroup analyses from statin and PCSK9 mAb trials to identify higher risk groups for which PCSK9 mAbs at the new price could be considered a reasonable (
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http://dx.doi.org/10.1016/j.jacl.2019.05.005DOI Listing
June 2020

Practice-level variation in statin use and low-density lipoprotein cholesterol control in the United States: Results from the Patient and Provider Assessment of Lipid Management (PALM) registry.

Am Heart J 2019 08 22;214:113-124. Epub 2019 May 22.

Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.

Background: Adherence to guideline-recommended statin recommendations in the United States is suboptimal. Patients' likelihood to be treated according to guidelines may vary by the practice in which they are treated.

Methods: Variation in the use of statin therapy in 5445 patients, with known or at high risk for atherosclerotic cardiovascular disease (ASCVD) and meeting a statin treatment indication, was examined across 74 US Patient and Provider Assessment of Lipid Management (PALM) Registry clinics. Multivariable generalized linear mixed modeling was used to determine the median odds ratio (MOR) for statin use and 2013 American College of Cardiology/American Heart Association guideline-recommended statin intensity by practice. MOR quantifies between-practice variation by comparing the odds of receiving guideline-recommended statin treatment in a patient from a randomly selected practice with a similar patient from another random practice. Risk-adjusted low-density lipoprotein cholesterol (LDL-C) control (<100 and <70 mg/dL) was compared among practice tertiles based on percentage of eligible patients receiving recommended statin intensity.

Results: Among 74 practices (43.2% cardiology) comprised of 300 healthcare providers enrolling 5445 patients (56.2% with ASCVD), statin use at the guideline-recommended intensity at practices varied widely (12.7-71.4%; adjusted MOR 1.45, 95% confidence interval [CI] 1.35-1.64). Results were consistent when evaluated for any statin use overall (adjusted MOR 1.75, 95% CI 1.48-1.99) and when stratified by primary versus secondary prevention patients. Relative to practices with lowest or mid-tertile statin use of statins, highest tertile clinics were more frequently cardiology practices (68.0% vs 48.0% vs 12.5%, P < .001). Compared with lowest tertile clinics, patients at highest tertile clinics were more likely to achieve LDL-C <70 mg/dL (adjusted odds ratio [OR] 1.49, 95% CI 1.08-2.04) and <100 mg/dL (adjusted OR 1.78, 95% CI 1.41-2.25).

Conclusions: US clinics varied widely in their adherence to guideline recommendations for statin therapy, which contributed to significant differences in LDL-C levels.
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http://dx.doi.org/10.1016/j.ahj.2019.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639125PMC
August 2019

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

Hum Mol Genet 2019 08;28(15):2615-2633

Icelandic Heart Association, Kopavogur, Iceland.

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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http://dx.doi.org/10.1093/hmg/ddz070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644157PMC
August 2019

The extent to which statins have improved cardiovascular outcomes: Lessons from randomized trials and observational studies of "real world" practice in people with diabetes.

Diabetes Obes Metab 2019 04;21 Suppl 1:17-27

College of Public Health, Carver College of Medicine, University of Iowa, Iowa City, Iowa.

Statins are the mainstay of therapy for cardiovascular risk reduction in patients with diabetes mellitus. It is estimated that there are more than half a billion patients with diabetes mellitus worldwide and the numbers of prevalent cases of diabetes are expected to increase in both developed and developing countries in the next decade. Statins reduce risk of mortality and morbidity mainly by reducing blood low density cholesterol. Statins, along with other medical treatments, are responsible for about half of the decrease in cardiovascular mortality over the past several decades. Multiple clinical trials have found evidence for statin use in patients with diabetes, for both primary prevention and secondary prevention. The benefit of statins in patients with coronary heart disease and diabetes in terms of absolute risk reduction is twice as much as compared to the risk in patients with coronary heart disease but no diabetes. The proportion of patients with diabetes treated with statins has increased steadily over the past few decades with concurrent decrease in cardiovascular deaths in this high-risk population. However, there are significant unmet needs in cardiovascular risk reduction, due to underutilization of statins and due to residual cardiovascular risk despite maximal statin therapy. Future strategies in population risk reduction in diabetics should include maximal statin therapy, additional treatment with nonstatin therapy and new paradigms of prevention with early intervention with shorter, more intensive therapy to potentially "reverse" atherosclerosis with goals of reducing clinical cardiovascular disease later in life.
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http://dx.doi.org/10.1111/dom.13701DOI Listing
April 2019