Abstract 16278: Discordant Lipid Phenotype and Other Determinants of Statin Response in the Pravastatin Inflammation/crp Evaluation (PRINCE) Trial

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Oluremi N Ajala ◽  
Olga Demler ◽  
Yanyan Liu ◽  
Paul M Ridker ◽  
Robert J Glynn ◽  
...  
Keyword(s):  
Moderate Intensity ◽  
Forward Selection ◽  
Cvd Risk ◽  
Double Blind ◽  
Apo B ◽  
Lipid Phenotype ◽  
Validation Of Models ◽  
Baseline Levels ◽  
Hs Crp ◽  
Statin Response

Introduction: Wide variability in LDL-C change is observed with statins, yet determinants of statin response are uncertain. Methods: Participants were selected from the primary prevention cohort of the Pravastatin Inflammation/CRP Evaluation double-blind trial that randomized participants to pravastatin 40 mg/d or placebo over 24 weeks. Baseline and 24-week levels of LDL-C and 15 other biomarkers were measured in 495 participants. We defined optimal statin response as >=30% LDL-C reduction and suboptimal response as <30% reduction. Sub-optimal hs-CRP response was defined as >=median (14%) decline in hs-CRP from baseline to 24 weeks and non-response as no decrease or an increase in hs-CRP. χ 2 , t-tests and ANOVA were used to compare variables across optimal statin response (N=166) and suboptimal response (N=287). Multivariable logistic regression models evaluated associations of determinants of statin response. Forward selection identified variables that associated with response. Xgboost was used to train and validate the models using 2/3 and 1/3 of the data respectively. Results: Significant determinants of optimal statin response included older age, and higher baseline levels of LDL-C and triglyceride-rich lipoproteins. By contrast, female sex, alcohol intake >=1 drink/day, diabetes, higher baseline levels of apo B and lipoprotein(a) were associated with decreased response, as was hs-CRP non-response (Table). Race, baseline hs-CRP and sub-optimal hs-CRP response, smoking, HDL-C and BMI had no significant effect on statin LDL-C response. Training and validation of models predicted suboptimal LDL-C response with an AUC of 0.71. Similarly, training and validation of models using Xgboost yielded an AUC of 0.85. Conclusion: This study identified discordant lipid phenotype and other determinants of moderate-intensity statin response and suggests other pathways of CVD risk beyond those addressed by statin treatment that require further investigation.

Abstract P260: Determinants of Statin Response: A Secondary Analysis of the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER)

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Oluremi N Ajala ◽  
Olga Demler ◽  
Yanyan Liu ◽  
Paul Ridker ◽  
Robert J Glynn ◽  
...  
Keyword(s):  
Secondary Analysis ◽  
Statin Treatment ◽  
Older Age ◽  
Multinomial Regression ◽  
Cvd Risk ◽  
Apo B ◽  
Markers Of Inflammation ◽  
Response Table ◽  
Baseline Levels ◽  
Statin Response

Introduction: Wide variability in LDLC change is observed with statins, yet determinants of statin response are uncertain. Hypotheses: Some markers of inflammation are associated with decreased statin response. Components of metabolic syndrome and older age are associated with better response. Methods: JUPITER (NCT00239681) randomized participants with LDLC<130 mg/dL and hs-CRP≥2 mg/L to rosuvastatin 20 mg/d or placebo. Baseline and 1-year levels of LDLC and a panel of 20 other biomarkers were measured. We defined optimal statin response as ≥50% LDLC reduction; suboptimal response as <50% reduction; and non-response as no change or increase in LDLC. χ 2 , t-tests and ANOVA were used to compare variables across optimal (N=3,801), suboptimal (N=3,235) and non-responders (N=868). Multinomial regression models evaluated associations of determinants of statin response after adjusting for risk factors including compliance. Backward selection identified variables that associated with response. t-distributed Stochastic Neighbor Embedding (t-SNE) suggested predictor clusters for statin response. Results: Compliance was the strongest determinant of statin response (Table). On multivariable analyses, blacks and Hispanics were at higher risk for suboptimal/non-response compared with whites as were greater alcohol use and HbA1c. Higher baseline levels of lipids [lipoprotein(a), apolipoprotein (apo) AI and B], inflammatory biomarkers, and lower branched-chain amino acids associated with decreased statin response (Table). By contrast, determinants of better response included older age, female sex, and higher waist circumference and baseline levels of LDLC, triglycerides, and blood pressure. We observed systematic patterns in t-SNE clustering for statin response by LDLC, LDL particle number, and apo B. Conclusions: This study identified determinants for high-intensity statin response and suggests other pathways of CVD risk beyond those addressed by statin treatment that require further investigation.

Abstract 682: Lapaqistat Acetate Monotherapy: Effects of a Novel Squalene Synthase Inhibitor on LDL-C Levels and Other Lipid Parameters in Patients with Primary Hypercholesterolemia

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Harold E Bays ◽  
Robert J Weiss ◽  
James M Rhyne ◽  
Yinzhong Chen ◽  
Claudia Lopez ◽  
...  
Keyword(s):  
Study Drug ◽  
Squalene Synthase ◽  
Phase Iii ◽  
Lipid Lowering ◽  
Controlled Study ◽  
Lipid Lowering Therapy ◽  
Double Blind ◽  
Apo B ◽  
Primary Hypercholesterolemia ◽  
Hs Crp

Background: Lapaquistat acetate (LAPA) inhibits squalene synthase, an important enzyme in the cholesterol biosynthetic pathway. Early studies showed that LAPA reduced LDL-C and improved lipid profiles in animals and humans. Methods: This multicenter, phase III, randomized, double-blind, parallel-group, placebo-controlled study assessed LAPA monotherapy in nondiabetic patients ≥ 18 yrs old with primary hypercholesterolemia (mean LDL-C > 130 mg/dL and < 220 mg/dL; mean triglyceride [TG] ≤400 mg/dL). Treatment-naïve patients or patients discontinuing previous lipid-lowering therapy underwent a 6-wk dietary stabilization period, then were randomized to 100 mg LAPA (n = 241) or Placebo (n = 120) once daily for 12 wks. The primary endpoint was percent (%) change from baseline compared with Placebo in direct LDL-C at Wk 12 or last on-treatment value. Secondary endpoints included: % change in calculated LDL-C, non-HDL-C, total cholesterol (TC), Apo B, HDL-C, VLDL-C, Apo A1, TG, and hs-CRP. Safety was monitored using clinical and laboratory examinations. Results: LAPA significantly reduced LDL-C levels (see Table ) within 2– 4 wks of treatment initiation that were maintained throughout the study. LDL-C remained relatively unchanged in the Placebo group. Compared with Placebo, LAPA lowered LDL-C levels 20.09% by end of study (p < 0.001). Non-HDL-C, TC, Apo B, VLDL-C, Apo A1, TG, and hs-CRP were also significantly reduced vs Placebo. Both the overall adverse event (AE) profile and the rate of AEs considered potentially related to study drug (~24%), were similar between treatment groups. Two serious AEs occurred in each group; the 2 SAEs in lapaquistat-treated patients were considered not related to study drug. Conclusion: LAPA (100 mg/day) monotherapy provided significant improvements in LDL-C, non-HDL-C, TC, Apo B, VLDL-C, TG, and hs-CRP levels, was generally safe and well tolerated, and potentially represents a novel treatment for hypercholesterolemic patients.

scholarly journals High Sensitivity C-Reactive Protein as Atherogenic Marker Among Type 2 Diabetes

2017 ◽  
Vol 13 (33) ◽  
pp. 403
Author(s):  
Abdelmarouf H. Mohieldein ◽  
Marghoob Hasan ◽  
Mahmoud I. El-Habiby
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Diabetic Patients ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Vascular Events ◽  
Apo B ◽  
Hs Crp

Background: People with type 2 diabetes are threefold affected by cardiovascular disease (CVD) compared with non-diabetics. Many studies reported the absence of traditional CVD risk factors in a substantial portion of individuals experiencing clinical vascular events. Novel risk markers for CVD are often said to add independent predictive value for risk prediction. Objective: In the present study we evaluated different CVD risk factors based on highsensitivity C-reactive (hs- CRP) protein quartiles among diabetics and nondiabetics population. Methods: In this population- based cross- sectional study, we recruited a total of onehundred and nine participants (64 type 2 diabetics and 45 healthy controls). Venous blood sample collected from each subject. Body weight and height were measured and body mass index (BMI) was calculated. Biochemical analytes were measured according to standard procedures. Data analyzed using SPSS software. Results: Mean serum hs-CRP levels were significantly higher among diabetics (2.3 mg/l) compared to controls (1.8 mg/l; P = 0.019). Moreover, the 3rd & 4th quartiles of hs-CRP were characterized by more frequency of diabetes as well as hypertension. The percent of participants with diabetes or hypertension seemed positively related to hs CRP concentrations. Lipid profile analysis revealed the highest levels of LDL-C and Apo B in 4th quartile hs-CRP. In addition, participants in the 4th quartile hs-CRP were characterized by the highest age, BMI, plasma glucose. However, there was European Scientific Journal November 2017 edition Vol.13, No.33 ISSN: 1857 – 7881 (Print) e - ISSN 1857- 7431 404 no clear association between levels of hs-CRP and the HbA1c, TC, TG, HDL-C, and Apo A1. Conclusion: Measurement of hs-CRP in diabetic patients might provide useful information for development of atherosclerosis and cardiovascular disease and help in early intervention.

scholarly journals Evaluation of LDL goal achievement in statin consumption, south east of Iran

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Malihe Aghasizadeh ◽  
Saeede Khosravi Bizhaem ◽  
Mahin Baniasadi ◽  
Mohammad Reza Khazdair ◽  
Toba Kazemi
Keyword(s):  
Cardiovascular Risk ◽  
Statin Therapy ◽  
Goal Achievement ◽  
Moderate Intensity ◽  
Cvd Risk ◽  
Intensity Pattern ◽  
Cross Sectional ◽  
Low Intensity ◽  
Very High ◽  
Statin Use

AbstractLipid goal achievement and statin consumption were estimated at extreme/very-high/high/moderate and low cardiovascular risk categories. In the cross-sectional study, 585 patients treated with statin therapy referring to the heart clinic of Birjand were recruited. Patients were classified and examined LDL-C values and the proportion reaching targets according to the American Association of Clinical Endocrinologists guideline. Three patterns of statin use (high/moderate/low-intensity statin therapy) in all patients were examined and attainments of LDL-C goal in cardiovascular risk groups have been demonstrated. Over half the populations (57.6%) were in the very-high CVD risk group. The results showed that the proportion of patients meeting total LDL-C goal values according to the guidelines was 43.4%. The frequency of patient had achievement LDL goal lower in high-intensity pattern (N = 13, 2.3%), compared with moderate (N = 496, 86.1%) and low-intensity patterns (N = 67, 11.6%). In general, LDL-C goal achievement was greatest with moderate-intensity statin use. LDL-C reduction after statin consumption was estimated about one-third of the studied population. It seems likely that the achievement of a therapeutic target for serum lipids such as LDL-C improved is far more cost-effective and would be able to reach the target LDL as well changing the type and intensity of statins.

scholarly journals The Effect of Dietary Nitrate Supplementation on Physiology and Performance in Trained Cyclists

2017 ◽  
Vol 12 (5) ◽  
pp. 684-689 ◽  
Author(s):  
Joseph A. McQuillan ◽  
Deborah K. Dulson ◽  
Paul B. Laursen ◽  
Andrew E. Kilding
Keyword(s):  
Time Trial ◽  
Crossover Design ◽  
Moderate Intensity ◽  
Beetroot Juice ◽  
Double Blind ◽  
Dietary Nitrate ◽  
Performance Time ◽  
Exercise Economy ◽  
Nitrate Supplementation ◽  
And Performance

Purpose:To determine the effect of dietary nitrate (NO3 –) supplementation on physiology and performance in well-trained cyclists after 6–8 d of NO3 – supplementation.Methods:Eight competitive male cyclists (mean ± SD age 26 ± 8 y, body mass 76.7 ± 6.9 kg, VO2peak 63 ± 4 mL · kg–1 · min–1) participated in a double-blind, placebo-controlled, crossover-design study in which participants ingested 70 mL of beetroot juice containing ~4 mmol NO3 – (NIT) or a NO3 –-depleted placebo (PLA), each for 8 d. Replicating pretreatment measures, participants undertook an incremental ramp assessment to determine VO2peak and first (VT1) and second (VT2) ventilatory thresholds on d 6 (NIT6 and PLA6), moderate-intensity cycling economy on d 7 (NIT7 and PLA7), and a 4-km time trial (TT) on d 8 (NIT8 and PLA8).Results:Relative to PLA, 6 d of NIT supplementation produced unclear effects for VO2peak (mean ± 95% confidence limit: 1.8% ± 5.5%) and VT1 (3.7% ± 12.3%) and trivial effects for both VT2 (–1.0% ± 3.0%) and exercise economy on d 7 (–1.0% ± 1.6%). However, effects for TT performance time (–0.7% ± 0.9%) and power (2.4% ± 2.5%) on d 8 were likely beneficial.Conclusions:Despite mostly unclear outcomes for standard physiological determinants of performance, 8 d of NO3 – supplementation resulted in likely beneficial improvements to 4-km TT performance in well-trained male endurance cyclists.

scholarly journals Moderate-intensity exercise reduces activated and apoptotic endothelial microparticles in healthy midlife women

2019 ◽  
Vol 126 (1) ◽  
pp. 102-110 ◽  
Author(s):  
Corinna Serviente ◽  
Amy Burnside ◽  
Sarah Witkowski
Keyword(s):  
Acute Exercise ◽  
Menopausal Status ◽  
Exploratory Analysis ◽  
Midlife Women ◽  
Repeated Measure ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Cvd Risk ◽  
Endothelial Microparticles ◽  
Healthy Midlife Women

Endothelial microparticles (EMPs) are related to cardiovascular disease (CVD) risk. Risk factors for CVD increase with menopause, and greater cardiorespiratory fitness is generally expected to reduce CVD risk. The effects of habitual physical activity on endothelial health may be due in part to the effect of acute exercise on circulating EMPs. This study was performed to evaluate the effect of an acute bout of exercise on CD62E+ and CD31+/42b− EMPs in healthy fit midlife women at different menopausal stages. Healthy, active premenopausal (PRE), perimenopausal (PERI), and postmenopausal (POST) women completed a single bout of moderate-intensity treadmill exercise. Activated (CD62E+) and apoptotic (CD31+/42b−) EMPs were evaluated before and 30 min after exercise by using fluorescent activated cell sorting. In an exploratory analysis, these results were compared with data from low-fit peri- and postmenopausal women. Differences by group and time point were evaluated with repeated-measure ANOVAs. There was a reduction in the number of total microparticles ( P < 0.001), CD62E+ ( P = 0.003), and CD31+/42b− ( P < 0.001) EMPs/μl plasma following acute exercise. The percentage of CD62E+ EMPs increased with acute exercise ( P < 0.001), whereas the percentage of CD31+/42b− EMPs did not change ( P = 0.40). There was no effect of menopausal status on CD62E+or CD31+/42b− EMPs, or on total microparticles (all P > 0.05). The exploratory analysis revealed that low-fit women had similar changes in EMPs with acute exercise. We concluded that acute moderate-intensity exercise reduces CD62E+and CD31+/42b− EMPs, as well as total microparticles, in healthy midlife women. These effects occurred despite differences in menopausal status and fitness. NEW & NOTEWORTHY This study demonstrates that acute moderate-intensity exercise reduces activated and apoptotic endothelial microparticles in healthy midlife women.

Abstract MP34: Tai Chi Exercise is More Effective Than Brisk Walking in Reducing Cardiovascular Disease Risk Factors

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Aileen W Chan ◽  
Doris Y Leung ◽  
SY Chair ◽  
Janet W Sit ◽  
Ruth E Taylor-Piliae
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Perceived Stress ◽  
Tai Chi ◽  
Disease Risk ◽  
Moderate Intensity ◽  
Brisk Walking ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Over Time

Background: Physical inactivity is one of the major modifiable lifestyle risk factors associated with cardiovascular disease (CVD). Tai Chi (TC) is safe and popular among older adults; yet direct comparisons between TC and brisk walking (BW) on reducing CVD risk factors are lacking. Methods: A total of 246 adults (mean age=64.4±9.8 years, 45.5% men) with hypertension and two other CVD risk factors (i.e., smoker, diabetic, dyslipidemia, or overweight) were randomly assigned to either TC (n=82), BW (n=82), or control (C, n=82) groups. The TC and BW groups had 150 minutes/week, moderate-intensity physical activity for three months; with home-based practice encouraged for another six months. The primary outcome was blood pressure (BP). Secondary outcomes were: fasting blood sugar (FBS), HbA1c, total cholesterol, triglycerides, high and low density lipoprotein, body mass index (BMI), waist circumference and perceived stress. Data were collected at baseline, post-intervention at 3-month, 6-month and 9-month follow-up assessments. Generalized estimating equations models compared changes in the outcomes over time between groups. Results: At baseline, average BP=141/81, smokers=11%, diabetics=58%, dyslipidemia=61%, average BMI=26; with no significant differences between groups. TC significantly lowered BP (systolic -13.33 mmHg; diastolic -6.45 mmHg), FBS (-0.72 mmol/L), HbA1c (-0.39%), and perceived stress (-3.22 score) at 9-months, compared to C group. Pairwise comparisons indicated significantly greater reductions in SBP (p<0.001), DBP (p=0.049), FBS (p=0.001), HbA1c (p=0.002), and perceived stress (p=0.027) in TC group, compared to BW group. No significant changes in other CVD risk indicators over time between groups were observed. Conclusion: TC was better than BW in reducing several CVD risk factors, and can be recommended as a viable exercise to build a healthier life free of CVD.

The Relationships of High-Sensitivity C-Reactive Protein and Homocysteine Levels With Disease Activity, Damage Accrual, and Cardiovascular Risk in Systemic Lupus Erythematosus

2019 ◽  
Vol 22 (2) ◽  
pp. 169-177 ◽  
Author(s):  
Gabriela Pocovi-Gerardino ◽  
Maria Correa-Rodríguez ◽  
José-Luis Callejas Rubio ◽  
Raquel Ríos Fernández ◽  
María Martín Amada ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
High Sensitivity ◽  
Cvd Risk Factors ◽  
Systemic Lupus ◽  
Cvd Risk ◽  
Damage Accrual ◽  
Hs Crp

Chronic inflammation coupled with cardiovascular disease (CVD) risk factors influences the progression of atherosclerosis in systemic lupus erythematosus (SLE). High-sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) are associated with the risk of CVD in the general population, but their associations with CV risk and disease activity in SLE are unclear. In this cross-sectional study ( N = 139 SLE patients, mean age = 45.27 ± 13.18 years), we investigated associations between hs-CRP and Hcy levels and disease activity, damage accrual, and CVD risk in SLE. Disease activity and damage accrual were measured with the SLE Activity Index 2000 (SLEDAI-2K), the Systemic Lupus Erythematosus International Collaborating Clinics Group/American College of Rheumatology damage index (SDI), and anti-double-stranded DNA antibodies (anti-dsDNA). CVD risk factors of obesity, diabetes mellitus, hypertension, blood lipids, and ankle–brachial index were collected. Linear regression analysis and one-way analysis of variance were used to analyze relationships of hs-CRP and Hcy with SLE activity, damage accrual, and CVD risk factors. Results: hs-CRP correlated significantly with SLEDAI-2K ( p = .036), SDI ( p = .00), anti-dsDNA titers ( p = .034), diabetes ( p = .005), and obesity ( p = .027). hs-CRP and Hcy correlated with triglyceride (TG) levels ( p = .032 and p < .001, respectively), TG/high-density lipoprotein cholesterol index ( p = .020 and p = .001, respectively), and atherogenic index of plasma ( p = .006 and p = .016, respectively). hs-CRP levels >3 mg/L correlated with SDI score ( p = .012) and several CVD risk factors. Discussion: Findings suggest SLE patients with elevated hs-CRP and/or Hcy have a higher prevalence of CVD risk factors.

Sign in / Sign up

Export Citation Format

Share Document