Browsing by Subject "Cholesterol, LDL"
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Item Open Access A protocol to evaluate the efficacy, perceptions, and cost of a cholesterol packaging approach to improve medication adherence.(Contemporary clinical trials, 2014-09) Zullig, Leah L; Pathman, Joshua; Melnyk, S Dee; Brown, Jamie N; Sanders, Linda L; Koropchak, Celine; Howard, Teresa; Danus, Susanne; McCant, Felicia; Bosworth, Hayden BPurpose
Elevated low-density lipoprotein cholesterol (LDL-C) is a major modifiable risk factor for cardiovascular disease (CVD), a leading cause of death in the United States. Despite clinical practice guidelines aimed at facilitating LDL-C control, many Veterans do not achieve guideline-recommended LDL-C levels.Methods
We describe a study focused on VA healthcare system users at risk for CVD (i.e., LDL-C level >130 mg/dl and/or <80% cholesterol pill refill adherence in the last 12 months). We are conducting a two and a half year randomized controlled trial (i.e., intervention administered over 12 months) among Veterans with uncontrolled cholesterol receiving care at select VA-affiliated primary care clinics in North Carolina. We anticipate enrolling 250 diverse patients (10% women; 40% African American). Patients are randomized to an educational control group or intervention group. Intervention group participants' medication is provided in special blister packaging labeled for daily use that includes reminders; MeadWestvaco Corporation's pre-filled DosePak® contains standard doses of statins in accordance with the existing prescriptions.Conclusions
Pre-filled blister packaging may provide an inexpensive solution to improve medication adherence. Our study enrolls a diverse sample and provides information about whether an adherence packaging intervention can: 1) improve medication adherence; 2) improve patients' LDL-C levels; 3) be well received by patients and providers; and 4) provide a cost effective solution to improve medication adherence.Item Open Access Design and rationale of the LAPLACE-TIMI 57 trial: a phase II, double-blind, placebo-controlled study of the efficacy and tolerability of a monoclonal antibody inhibitor of PCSK9 in subjects with hypercholesterolemia on background statin therapy.(Clinical cardiology, 2012-01) Kohli, Payal; Desai, Nihar R; Giugliano, Robert P; Kim, Jae B; Somaratne, Ransi; Huang, Fannie; Knusel, Beat; McDonald, Shannon; Abrahamsen, Timothy; Wasserman, Scott M; Scott, Robert; Sabatine, Marc SLowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone for the prevention of atherosclerotic heart disease, improving clinical outcomes and reducing vascular mortality in patients with hypercholesterolemia. The clinical benefits of LDL-C reduction appear to extend even to patients starting with LDL-C as low as 60-80 mg/dL prior to initiating therapy. Statins are the first-line agents for treating hypercholesterolemia and are effective in reducing LDL-C, but many patients are unable to achieve their optimal lipid targets despite intensive statin therapy. Therefore, there has been a strong impetus for the development of novel pharmacologic agents designed to lower LDL-C further in patients already on statin therapy. Genetic mutations resulting in altered cholesterol homeostasis provide valuable information regarding novel approaches for treating hypercholesterolemia. To that end, mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) were linked to altered levels of LDL-C, illustrating this protein's role in lipid metabolism. PCSK9 promotes degradation of the LDL receptor, preventing its transport back to the cell surface and thereby increasing circulating LDL-C. Conversely, inhibition of PCSK9 can profoundly decrease circulating LDL-C, and thus is an attractive new target for LDL-C-lowering therapy. AMG 145 is a fully human monoclonal immunoglobulin G2 antibody that binds specifically to human PCSK9 and inhibits its interaction with the low-density lipoprotein receptor. In this manuscript, we describe the rationale and design of LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-Thrombolysis In Myocardial Infarction 57 (LAPLACE-TIMI 57; NCT01380730), a 12-week, randomized, double-blind, dose-ranging, placebo-controlled study designed to assess the safety and efficacy of AMG 145 when added to statin therapy in patients with hypercholesterolemia.Item Open Access Evaluation of a packaging approach to improve cholesterol medication adherence.(The American journal of managed care, 2017-09) Bosworth, Hayden B; Brown, Jamie N; Danus, Susanne; Sanders, Linda L; McCant, Felicia; Zullig, Leah L; Olsen, Maren KElevated low-density lipoprotein cholesterol (LDL-C) is a major modifiable risk factor for cardiovascular disease, a leading cause of death in the United States. Our goal was to evaluate a simple, scalable, and affordable medication packaging method for improving cholesterol medication adherence and subsequently lowering LDL-C levels.Mixed-method study.This mixed-method study involved US military veterans with LDL-C levels greater than 130 mg/dL and/or less than 80% refill adherence of cholesterol-lowering medication in the last 12 months; they were randomized to an education-only (control) group or an adherence packaging intervention group. Adherence packaging group participants' statin medication was provided in special blister packaging labeled for daily use that included written reminder prompts. Outcomes included 12-month cholesterol medication possession ratio (MPR) for medication refills; baseline, 6-, and 12-month self-reported cholesterol medication use; LDL-C and high-density lipoprotein cholesterol (HDL-C) levels; and total cholesterol changes over 12 months. Qualitative evaluation of the intervention is presented as well.We enrolled 240 individuals (120 intervention, 120 control). Overall, 54.2% of the adherence packaging intervention group was adherent per MPR over 12 months compared with 46.6% of the education-only group (difference = 7.6%; 95% confidence interval, -5% to 20%; P ≤.24). Both arms reported improvements in self-reported cholesterol adherence at 12 months, and decreases in LDL-C, HDL-C, and total cholesterol were observed, but differences in change between arms were not statistically significant. Qualitatively, patients reported high levels of satisfaction with the blister package.In a sample of US veterans, prefilled calendared blister packaging provided an inexpensive method for improving cholesterol medication adherence.Item Open Access Heart matters: Gender and racial differences cardiovascular disease risk factor control among veterans.(Women's health issues : official publication of the Jacobs Institute of Women's Health, 2014-09) Goldstein, Karen M; Melnyk, S Dee; Zullig, Leah L; Stechuchak, Karen M; Oddone, Eugene; Bastian, Lori A; Rakley, Susan; Olsen, Maren K; Bosworth, Hayden BBackground
Cardiovascular disease (CVD) is the leading cause of mortality for U.S. women. Racial minorities are a particularly vulnerable population. The increasing female veteran population has an higher prevalence of certain cardiovascular risk factors compared with non-veteran women; however, little is known about gender and racial differences in cardiovascular risk factor control among veterans.Methods
We used analysis of variance, adjusting for age, to compare gender and racial differences in three risk factors that predispose to CVD (diabetes, hypertension, and hyperlipidemia) in a cohort of high-risk veterans eligible for enrollment in a clinical trial, including 23,955 men and 1,010 women.Findings
Low-density lipoprotein (LDL) values were higher in women veterans than men with age-adjusted estimated mean values of 111.7 versus 97.6 mg/dL (p < .01). Blood pressures (BPs) were higher among African-American than White female veterans with age-adjusted estimated mean systolic BPs of 136.3 versus 133.5 mmHg, respectively (p < .01), and diastolic BPs of 82.4 versus 78.9 mmHg (p < .01). African-American veterans with diabetes had worse BP, LDL values, and hemoglobin A1c levels, although the differences were only significant among men.Conclusions
Female veterans have higher LDL cholesterol levels than male veterans and African-American veterans have higher BP, LDL cholesterol, and A1c levels than Whites after adjusting for age. Further examination of CVD gender and racial disparities in this population may help to develop targeted treatments and strategies applicable to the general population.Item Open Access HIV and Hepatitis C-Coinfected Patients Have Lower Low-Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent "PCSK9-Lipid Paradox".(Journal of the American Heart Association, 2016-04) Kohli, Payal; Ganz, Peter; Ma, Yifei; Scherzer, Rebecca; Hur, Sophia; Weigel, Bernard; Grunfeld, Carl; Deeks, Steven; Wasserman, Scott; Scott, Rob; Hsue, Priscilla YBackground
Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and improve outcomes in the general population. HIV-infected individuals are at increased risk for cardiovascular events and have high rates of dyslipidemia and hepatitis C virus (HCV) coinfection, making PCSK9 inhibition a potentially attractive therapy.Methods and results
We studied 567 participants from a clinic-based cohort to compare PCSK9 levels in patients with HIV/HCV coinfection (n=110) with those with HIV infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median LDL-C level was 100 mg/dL (IQR 77-124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors. Total cholesterol, LDL-C, and high-density lipoprotein cholesterol levels were lower in coinfected patients compared with controls (P<0.001). PCSK9 was 21% higher in HIV/HCV-coinfected patients versus controls (95% CI 9-34%, P<0.001) and 11% higher in coinfected individuals versus those with HIV infection alone (95% CI 3-20%, P=0.008). After adjustment for cardiovascular risk factors, HIV/HCV coinfection remained significantly associated with 20% higher PCSK9 levels versus controls (95% CI 8-33%, P=0.001). Interleukin-6 levels increased in a stepwise fashion from controls (lowest) to HIV-infected to HIV/HCV-coinfected individuals (highest) and correlated with PCSK9 (r=0.11, P=0.018).Conclusions
Despite having lower LDL-C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin-6. Clinical trials should be conducted to determine the efficacy of targeted PCSK9 inhibition in the setting of HIV/HCV coinfection.Item Open Access Impact of Gender on Satisfaction and Confidence in Cholesterol Control Among Veterans at Risk for Cardiovascular Disease.(Journal of women's health (2002), 2017-07) Goldstein, Karen M; Stechuchak, Karen M; Zullig, Leah L; Oddone, Eugene Z; Olsen, Maren K; McCant, Felicia A; Bastian, Lori A; Batch, Bryan C; Bosworth, Hayden BBackground
Compared with men, women have poorer lipid control. Although potential causes of this disparity have been explored, it is unknown whether patient-centered factors such as satisfaction and confidence contribute. We evaluated (1) whether satisfaction with lipid control and confidence in ability to improve it vary by gender and (2) whether sociodemographic characteristics modify the association.Materials and methods
We evaluated baseline survey responses from the Cardiovascular Intervention Improvement Telemedicine Study, including self-rated satisfaction with cholesterol levels and confidence in controlling cholesterol. Participants had poorly controlled hypertension and/or hypercholesterolemia.Results
A total of 428 veterans (15% women) participated. Compared with men, women had higher low-density lipoprotein values at 141.2 versus 121.7 mg/dL, respectively (p < 0.05), higher health literacy, and were less likely to have someone to help track their medications (all p < 0.05). In an adjusted model, women were less satisfied with their cholesterol levels than men with estimated mean scores of 4.3 versus 5.6 on a 1-10 Likert scale (p < 0.05). There was no significant difference in confidence by gender. Participants with support for tracking medications reported higher confidence levels than those without, estimated mean 7.8 versus 7.2 (p < 0.05).Conclusions
Women veterans at high risk for cardiovascular disease were less satisfied with their lipid control than men; however, confidence in ability to improve lipid levels was similar. Veterans without someone to help to track medications were less confident, and women were less likely to have this type of social support. Lack of social support for medication tracking may be a factor in lingering gender-based disparities in hyperlipidemia.Item Open Access Low-density lipoprotein cholesterol and survival in pulmonary arterial hypertension.(Scientific reports, 2017-02-15) Kopeć, Grzegorz; Waligóra, Marcin; Tyrka, Anna; Jonas, Kamil; Pencina, Michael J; Zdrojewski, Tomasz; Moertl, Deddo; Stokwiszewski, Jakub; Zagożdżon, Paweł; Podolec, PiotrLow-density lipoprotein cholesterol(LDL-C) is a well established metabolic marker of cardiovascular risk, however, its role in pulmonary arterial hypertension (PAH) has not been determined. Therefore we assessed whether LDL-C levels are altered in PAH patients, if they are associated with survival in this group and whether pulmonary hypertension (PH) reversal can influence LDL-C levels. Consecutive 46 PAH males and 94 females were age matched with a representative sample of 1168 males and 1245 females, respectively. Cox regression models were used to assess the association between LDL-C and mortality. The effect of PH reversal on LDL-C levels was assessed in 34 patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing invasive treatment. LDL-C was lower in both PAH (2.6 ± 0.8 mmol/l) and CTEPH (2.7 ± 0.7 mmol/l) patients when compared to controls (3.2 ± 1.1 mmol/l, p < 0.001). In PAH patients lower LDL-C significantly predicted death (HR:0.44/1 mmol/l, 95%CI:0.26-0.74, p = 0.002) after a median follow-up time of 33(21-36) months. In the CTEPH group, LDL-C increased (from 2.6[2.1-3.2] to 4.0[2.8-4.9]mmol/l, p = 0.01) in patients with PH reversal but remained unchanged in other patients (2.4[2.2-2.7] vs 2.3[2.1-2.5]mmol/l, p = 0.51). We concluded that LDL-C level is low in patients with PAH and is associated with an increased risk of death. Reversal of PH increases LDL-C levels.Item Open Access Low-density lipoprotein cholesterol was inversely associated with 3-year all-cause mortality among Chinese oldest old: data from the Chinese Longitudinal Healthy Longevity Survey.(Atherosclerosis, 2015-03) Lv, Yue-Bin; Yin, Zhao-Xue; Chei, Choy-Lye; Qian, Han-Zhu; Kraus, Virginia Byers; Zhang, Juan; Brasher, Melanie Sereny; Shi, Xiao-Ming; Matchar, David Bruce; Zeng, YiObjective
Low-density lipoprotein cholesterol (LDL-C) is a risk factor for survival in middle-aged individuals, but conflicting evidence exists on the relationship between LDL-C and all-cause mortality among the elderly. The goal of this study was to assess the relationship between LDL-C and all-cause mortality among Chinese oldest old (aged 80 and older) in a prospective cohort study.Methods
LDL-C concentration was measured at baseline and all-cause mortality was calculated over a 3-year period. Multiple statistical models were used to adjust for demographic and biological covariates.Results
During three years of follow-up, 447 of 935 participants died, and the overall all-cause mortality was 49.8%. Each 1 mmol/L increase of LDL-C concentration corresponded to a 19% decrease in 3-year all-cause mortality (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.71-0.92). The crude HR for abnormally higher LDL-C concentration (≥3.37 mmol/L) was 0.65 (0.41-1.03); and the adjusted HR was statistically significant around 0.60 (0.37-0.95) when adjusted for different sets of confounding factors. Results of sensitivity analysis also showed a significant association between higher LDL-C and lower mortality risk.Conclusions
Among the Chinese oldest old, higher LDL-C level was associated with lower risk of all-cause mortality. Our findings suggested the necessity of re-evaluating the optimal level of LDL-C among the oldest old.Item Open Access Secondary prevention risk interventions via telemedicine and tailored patient education (SPRITE): a randomized trial to improve postmyocardial infarction management.(Circulation. Cardiovascular quality and outcomes, 2011-03) Shah, Bimal R; Adams, Martha; Peterson, Eric D; Powers, Benjamin; Oddone, Eugene Z; Royal, Kira; McCant, Felicia; Grambow, Steven C; Lindquist, Jennifer; Bosworth, Hayden BBackground
Secondary prevention by risk factor modification improves patient outcomes, yet it is often not achieved in clinical practice. Reasons for failure stem from challenges of prioritizing risk factor reduction and engaging patients in changing their behaviors. We hypothesize that a novel telemedicine intervention with tailored patient education could improve cardiovascular risk factors.Methods
To evaluate this intervention, we propose enrolling 450 patients with a recent myocardial infarction and hypertension into a 3-arm randomized, controlled trial. The first arm (n=150) will receive home blood pressure (BP) monitors plus a nurse-delivered, telephone-based tailored patient education intervention and will be enrolled into HealthVault, a Microsoft electronic health record platform. The second arm (n=150) will also receive BP monitors plus a tailored patient education intervention and be enrolled in HeartVault. However, the patient education intervention will be delivered by a Web-based program and will cover topics identical to those in the nurse-delivered intervention. Both arms will be compared with a control group receiving standard care (n=150). All participants will have an in-person assessment at baseline and at completion of the study, including standardized measurements of BP, LDL cholesterol, and glycosylated hemoglobin (in diabetic subjects). The study design will allow assessment of a telephone-based, nurse-administered disease management program versus standard care. The main outcome of interest is the reduction in systolic BP in each intervention group compared with the control group at 12 months. Secondary outcomes assessed will include reductions in LDL cholesterol, body weight, and glycosylated hemoglobin, as well as adherence to evidence-based therapies and improvement in health behaviors.Conclusion
If successful in optimizing BP control, managing other coronary heart disease risk factors, and demonstrating a lower cost, the Web-based disease management tool has the potential to enhance coronary artery disease management, quality of care, and ultimately, patient outcomes. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00901277.Item Open Access Study protocol: the Adherence and Intensification of Medications (AIM) study--a cluster randomized controlled effectiveness study.(Trials, 2010-10-12) Heisler, Michele; Hofer, Timothy P; Klamerus, Mandi L; Schmittdiel, Julie; Selby, Joe; Hogan, Mary M; Bosworth, Hayden B; Tremblay, Adam; Kerr, Eve ABACKGROUND: Many patients with diabetes have poor blood pressure (BP) control. Pharmacological therapy is the cornerstone of effective BP treatment, yet there are high rates both of poor medication adherence and failure to intensify medications. Successful medication management requires an effective partnership between providers who initiate and increase doses of effective medications and patients who adhere to the regimen. METHODS: In this cluster-randomized controlled effectiveness study, primary care teams within sites were randomized to a program led by a clinical pharmacist trained in motivational interviewing-based behavioral counseling approaches and authorized to make BP medication changes or to usual care. This study involved the collection of data during a 14-month intervention period in three Department of Veterans Affairs facilities and two Kaiser Permanente Northern California facilities. The clinical pharmacist was supported by clinical information systems that enabled proactive identification of, and outreach to, eligible patients identified on the basis of poor BP control and either medication refill gaps or lack of recent medication intensification. The primary outcome is the relative change in systolic blood pressure (SBP) measurements over time. Secondary outcomes are changes in Hemoglobin A1c, low-density lipoprotein cholesterol (LDL), medication adherence determined from pharmacy refill data, and medication intensification rates. DISCUSSION: Integration of the three intervention elements--proactive identification, adherence counseling and medication intensification--is essential to achieve optimal levels of control for high-risk patients. Testing the effectiveness of this intervention at the team level allows us to study the program as it would typically be implemented within a clinic setting, including how it integrates with other elements of care. TRIAL REGISTRATION: The ClinicalTrials.gov registration number is NCT00495794.Item Open Access The effect of a nurse-led telephone-based care coordination program on the follow-up and control of cardiovascular risk factors in patients with coronary artery disease.(International journal for quality in health care : journal of the International Society for Quality in Health Care, 2016-12) Wong, Ningyan; Chua, Siang Jin Terrance; Gao, Fei; Sim, Sok Tiang Rosalind; Matchar, David; Wong, Sung Lung Aaron; Yeo, Khung Keong; Tan, Wei Chieh Jack; Chin, Chee TangObjective
We sought to analyse the impact of a care coordination protocol on transiting patients with coronary artery disease who had undergone percutaneous coronary intervention (PCI) to primary care and its effect on cardiovascular risk factor control.Design
A prospective observational study involving 492 patients who had undergone PCI either electively or after an acute coronary syndrome.Setting
A tertiary institution in Singapore.Participants
Patients who had undergone a PCI either electively or after an acute coronary syndrome.Interventions
The SCORE (Standardized Care for Optimal Outcomes, Right-Siting and Rapid Re-evaluation) program was a nurse-led, telephone-based, care coordination protocol.Main outcome measures
Transition to primary care within 1 year of enrolment, the achievement of low-density lipoprotein (LDL) level of <2.6 mmol/l within 1 year and hospital admissions related to cardiovascular causes within 1 year were studied.Results
Under the SCORE protocol, a significantly higher number of patients transited to primary care and achieved the LDL target within 1 year, as compared with non-SCORE patients. Discharge to primary care and achievement of target LDL continued to be higher among those under the SCORE protocol even after multivariate analysis. Rates of hospital admission due to cardiovascular causes were not significantly different.Conclusions
Care coordination improved the rate of transition of post-PCI patients to primary care and improved LDL control, with no difference in the rate of hospital admissions due to cardiovascular causes. These findings support the implementation of a standardized follow-up protocol in patients who have undergone PCI.Item Open Access The trials and tribulations of enrolling couples in a randomized, controlled trial: a self-management program for hyperlipidemia as a model.(Patient education and counseling, 2011-07) Voils, Corrine I; Yancy, William S; Weinberger, Morris; Bolton, Jamiyla; Coffman, Cynthia J; Jeffreys, Amy; Oddone, Eugene Z; Bosworth, Hayden BObjective
Capitalizing on spousal support may enhance the effectiveness of interventions for chronic disease management. However, couples-based interventions present logistical challenges. We describe our experience and lessons learned while recruiting couples into the Couples Partnering for Lipid-Enhancing Strategies (CouPLES) trial.Methods
This trial seeks to reduce serum low-density lipoprotein cholesterol levels using a couples-based intervention designed to help patients engage in self-management behaviors. We proposed enrolling 250 couples over 13 months.Results
Due to practical challenges that we encountered, recruitment and enrollment lasted 21 months. Those challenges included: travel to study site; effectively marketing the study; participant burden; and establishing eligibility criteria. By modifying our protocol to address these challenges, the recruitment rate increased from 12 to 33%.Conclusion
In the absence of trials identifying the most effective recruitment strategies, investigators may need to experiment, amending their protocol intermittently until target enrollment numbers are reached. The lessons we present may help researchers conducting couples-based interventions develop more effective protocols.Practice implications
To achieve target enrollment numbers, researchers conducting couples-based interventions should consider minimizing travel to the study site; carefully crafting recruitment materials; budgeting more for participant incentives and staff effort; and limiting exclusion criteria. These practices may also enhance retention.Item Open Access Therapy and clinical trials.(Curr Opin Lipidol, 2013-06) Sodhi, Nishtha; Krasuski, Richard AItem Open Access Whole genome sequence analysis of blood lipid levels in >66,000 individuals.(Nature communications, 2022-10) Selvaraj, Margaret Sunitha; Li, Xihao; Li, Zilin; Pampana, Akhil; Zhang, David Y; Park, Joseph; Aslibekyan, Stella; Bis, Joshua C; Brody, Jennifer A; Cade, Brian E; Chuang, Lee-Ming; Chung, Ren-Hua; Curran, Joanne E; de Las Fuentes, Lisa; de Vries, Paul S; Duggirala, Ravindranath; Freedman, Barry I; Graff, Mariaelisa; Guo, Xiuqing; Heard-Costa, Nancy; Hidalgo, Bertha; Hwu, Chii-Min; Irvin, Marguerite R; Kelly, Tanika N; Kral, Brian G; Lange, Leslie; Li, Xiaohui; Lisa, Martin; Lubitz, Steven A; Manichaikul, Ani W; Michael, Preuss; Montasser, May E; Morrison, Alanna C; Naseri, Take; O'Connell, Jeffrey R; Palmer, Nicholette D; Palmer, Nicholette D; Peyser, Patricia A; Reupena, Muagututia S; Smith, Jennifer A; Sun, Xiao; Taylor, Kent D; Tracy, Russell P; Tsai, Michael Y; Wang, Zhe; Wang, Yuxuan; Bao, Wei; Wilkins, John T; Yanek, Lisa R; Zhao, Wei; Arnett, Donna K; Blangero, John; Boerwinkle, Eric; Bowden, Donald W; Chen, Yii-Der Ida; Correa, Adolfo; Cupples, L Adrienne; Dutcher, Susan K; Ellinor, Patrick T; Fornage, Myriam; Gabriel, Stacey; Germer, Soren; Gibbs, Richard; He, Jiang; Kaplan, Robert C; Kardia, Sharon LR; Kim, Ryan; Kooperberg, Charles; Loos, Ruth JF; Viaud-Martinez, Karine A; Mathias, Rasika A; McGarvey, Stephen T; Mitchell, Braxton D; Nickerson, Deborah; North, Kari E; Psaty, Bruce M; Redline, Susan; Reiner, Alexander P; Vasan, Ramachandran S; Rich, Stephen S; Willer, Cristen; Rotter, Jerome I; Rader, Daniel J; Lin, Xihong; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; Peloso, Gina M; Natarajan, PradeepBlood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids.