Coronary Heart Disease Risk Reduction Research Articles

Event-free FH patients >65 years of age are characterized by higher concentration of large HDL particles

Background and Aims: Familial hypercholesterolemia (FH) is a genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C) and premature coronary heart disease (CHD). Cholesterol-lowering therapy (statins) reduces CHD risk, but have only been available for the last 25 years, thus, elderly (>65 years) FH patients have been untreated several decades of their life. Surprisingly, some of these have never experienced any CHD event, raising the question whether they present CHD-resistant characteristics. To our knowledge, there are no reports of comprehensive metabolite profiling in these individuals. Therefore, we aimed to characterize metabolic differences between elderly FH subjects with and without CHD.

Effects of cardiac rehabilitation with and without meditation on myocardial blood flow using quantitative positron emission tomography: A pilot study

BackgroundPsychosocial stress is recognized as a risk factor for coronary heart disease (CHD). High rates of CHD in African-Americans may be related to psychosocial stress. However, standard cardiac rehabilitation (CR) usually does not include a systematic stress-reduction technique. Previous studies suggest that the Transcendental Meditation (TM) technique may reduce CHD risk factors and clinical events. This pilot study explored the effects of standard CR with and without TM on a measure of CHD in African-American patients. MethodsFifty-six CHD patients were assigned to CR, CR + TM, TM alone, or usual care. Testing was done at baseline and after 12 weeks. The primary outcome was myocardial flow reserve (MFR) assessed by 13N-ammonia positron emission tomography (PET). Secondary outcomes were CHD risk factors. Based on guidelines for analysis of small pilot studies, data were analyzed for effect size (ES). ResultsFor 37 patients who completed posttesting, there were MFR improvements in the CR + TM group (+20.7%; ES = 0.64) and the TM group alone (+12.8%; ES = 0.36). By comparison, the CR-alone and usual care groups showed modest changes (+ 5.8%; ES = 0.17 and − 10.3%; ES = − 0.31), respectively. For the combined TM group, MFR increased (+ 14%, ES = 0.56) compared to the combined non-TM group (− 2.0%, ES = − 0.08). ConclusionsThese pilot data suggest that adding the TM technique to standard cardiac rehabilitation or using TM alone may improve the myocardial flow reserve in African-American CHD patients. These results may be applied to the design of controlled clinical trials to definitively test these effects. Trial registrationClinicalTrials.gov registration # NCT01810029.

Lignan Intake and Risk of Coronary Heart Disease

BackgroundEvidence regarding lignan consumption in relation to coronary heart disease (CHD) risk remains limited and mixed. ObjectivesThe aim of this study was to prospectively examine associations between lignan intake and CHD risk in U.S. men and women. MethodsWe prospectively followed 214,108 men and women in 3 cohorts who did not have cardiovascular disease or cancer at baseline. Diet was repeatedly assessed using a validated food frequency questionnaire every 2-4 years since baseline. ResultsDuring 5,517,225 person-years of follow-up, we documented 10,244 CHD cases, including 6,283 nonfatal myocardial infarction and 3,961 fatal CHD cases. In multivariable-adjusted analyses, comparing extreme quintiles, the pooled hazard ratios of CHD were 0.85 (95% CI: 0.79-0.92) for total lignans, 0.76 (95% CI: 0.71-0.82) for matairesinol, 0.87 (95% CI: 0.81-0.93) for secoisolariciresinol, 0.89 (95% CI: 0.83-0.95) for pinoresinol, and 0.89 (95% CI: 0.83-0.95) for lariciresinol (all P values for trend ≤0.003). Nonlinear relationships were found for total lignan, matairesinol, and secoisolariciresinol: the risk reduction plateaued at intakes above approximately 300 μg/d, 10 μg/d, and 100 μg/d, respectively (P < 0.01 for all nonlinearity). The inverse associations for total lignan intake appeared to be more apparent among participants with higher total fiber intake (P = 0.04 for interaction). In addition, lignan intake was more strongly associated with plasma concentrations of enterolactone when fiber intake was higher. ConclusionsIncreased long-term intake of lignans was associated with a significantly lower risk of total CHD in both men and women. Possible synergistic effects may exist between lignan and fiber intake in relation to CHD risk reduction, possibly through enhancing the production of enterolignans.

High-Density Lipoprotein Subfractions: Much Ado about Nothing or Clinically Important?

High-density lipoproteins (HDL) are a heterogenous group of plasma molecules with a large variety in composition. There is a wide specter in lipid content and the number of different proteins that has been associated with HDL is approaching 100. Given this heterogeneity and the fact that the total amount of HDL is inversely related to the risk of coronary heart disease (CHD), there has been increasing interest in the function of specific HDL subgroups and in what way measuring and quantifying these subgroups could be of clinical importance in determining individual CHD risk. If certain subgroups appear to be more protective than others, it may also in the future be possible to pharmacologically increase beneficial and decrease harmful subgroups in order to reduce CHD risk. In this review we give a short historical perspective, summarize some of the recent clinical findings regarding HDL subclassifications and discuss why such classification may or may not be of clinical relevance.

Acupuncture Treatment Reduced the Risk of Coronary Heart Disease in Patients with Depression: A Propensity-Score Matched Cohort Study.

BackgroundMajor depressive disorder is a significant public health concern, which often leads to loss of productivity, functional decline, and various complications. The aim of this study was to investigate the effectiveness of acupuncture in the risk reduction of coronary heart disease (CHD) in patients with depression.MethodsWe enrolled patients diagnosed with depression between January 1, 1997, and December 31, 2010, through the Taiwanese National Health Insurance Research Database (NHIRD). Propensity score was used to match equal numbers (n=14,647) of acupuncture cohort and no-acupuncture cohort based on characteristics including sex, age, baseline comorbidity and medication. Patients were followed up until December 31, 2013, or withdrawn from the NHIRD. The Cox regression model was used to compare the hazard ratios (HRs) of CHD in the two cohorts.ResultsThe basic characteristics of the two groups were similar. A lower cumulative incidence of CHD was noted in the acupuncture cohort (Log rank test, p < 0.001). Over time, 1626 patients in the acupuncture cohort (21.05 per 1000 person-years) and 2412 patients in the no-acupuncture cohort (39.84 per 1000 person-years) developed CHD (adjusted HR=0.50, 95% CI 0.47–0.53). The decreased CHD incidence was independent of age, sex, comorbidities, and medications used. The cumulative incidence of CHD was significantly lower in the acupuncture cohort than in the no-acupuncture cohort (Log rank test, p<0.001).ConclusionThe results provided a real-world evidence that acupuncture may have beneficial effect on CHD risk reduction in patients with depression.

Anti-inflammatory activity of the Tongmai Yangxin pill in the treatment of coronary heart disease is associated with estrogen receptor and NF-κB signaling pathway

Ethnopharmacological relevanceThe Tongmai Yangxin Pill (TMYX) is a patented traditional Chinese medicine originating from two classic prescriptions, Zhigancao Decoction and Shenmai Yin, which composed of 11 Chinese medicinal herbs: Rehmannia glutinosa (Gaertn.) DC., Spatholobus suberectus Dunn, Ophiopogon japonicus (Thunb.) Ker Gawl., Glycyrrhiza uralensis Fisch., Polygonum multiflorum Thunb., Equus asinus L., Schisandra chinensis (Turcz.) Baill., Codonopsis pilosula (Franch.) Nannf., Chinemys reevesii (Gray), Ziziphus jujuba Mill. and Cinnamomum cassia (L.) J.Presl (Committee of the Pharmacopoeia of PR China, 2015). TMYX has marketed in China for the treatment of chest pain, palpitation, angina, irregular heartbeat and coronary heart disease (CHD) for several decades. Previous studies have confirmed that TMYX can treat CHD by reducing inflammation, but the underlying pharmacological mechanism remains unclear. Aim of the studyThis study aimed to declare the underlying pharmacological mechanism of anti-inflammatory activity of TMYX in the treatment of CHD via clinical trial, microarray study, bioinformatics analysis and the vitro assays. Materials and methodsEight CHD patients’ serum biochemical indices including coagulation function, lipid metabolism, endothelial injury, metalloprotease, adhesion molecule, inflammatory mediator and homocysteine were measured to investigate the reduction of CHD risk by TMYX oral administration (40 pills/time, 2 times/day) for eight weeks. The expression profile chips and Ingenuity Pathway Analysis (IPA) were assessed to reveal the global transcriptional response and predict related functions, diseases and canonical pathways. The in vitro anti-inflammatory actions of TMYX were evaluated using oxidized low-density lipoprotein (100 μg/mL) induced murine RAW264.7 macrophage with an ethanol extract from TMYX (EETMYX) (25–100 μg/mL). ResultsTMYX treatment showed reduced levels of apolipoprotein B, endothelin 1, nuclear factor κB (NF-κB) and homocysteine in CHD patients. In contrast, the treatment increased the ratio of apolipoprotein A/apolipoprotein B. EETMYX restored cell morphology and suppressed the lipid deposition of the induced foam cells. EETMYX exerted anti-inflammatory effects by raising the mRNA and protein expression of Estrogen receptor 1 (ESR1), blocking the reduction of IκBa level and the phosphorylation of IKKα/β, IκBα and NF-κB p65, accompanied by inhibiting MCP-1, TNF-α and IL-6 production, which were consistent with bioinformatics predictions. ConclusionTMYX treatment improved the biochemical indices in CHD patients. EETMYX effectively attenuated macrophage foam cell formation and exhibited anti-inflammatory activity is associated with regulating ESR1 and NF-κB signaling pathway activity.

Decrease of coronary heart disease risk with GLP1-receptor agonists or SGLT2 inhibitors therapy in patients with type 2 diabetes in primary cardiovascular prevention: A 24 months follow-up study

AimsThe aim of this real-world study is to evaluate the effect of glucagon-like peptide1 receptor-agonist (GLP1 RA) and sodium-glucose co-transporter2 inhibitor (SGLT2i) on coronary heart disease (CHD) risk, in patients with type 2 diabetes (T2D) in primary cardiovascular prevention. MethodsData from 312 patients with T2D, without CHD history, starting treatment with GLP1 RA (n = 174) or SGLT2i (n = 138), were retrospectively collected. UKPDS-RE score was used to estimate 10-years risk for CHD before and 6, 12 and 24 months after prescription. ResultsThe 10-year CHD risk significantly decreased over 24 months in both GLP1 RA and SGLT2i groups (p = 0.037 and p < 0.001, respectively), with 3% and 7% CHD risk reduction already obtained after the first 6 months of GLP1 RA and SGLT2i therapy respectively (p < 0.001 in both groups. Analyses by categories of baseline CHD risk showed significant reductions of CHD risk in the severe risk categories of both groups (p < 0.001). CHD risk reduction obtained with SGLT2i was higher than with GLP1 RA at 6 and 12 months but not at 24 months. ConclusionThis real-world study shows that both GLP1 RA and SGLT2i reduce the 10-year risk for cardiovascular disease in patients with T2D in primary cardiovascular prevention.

Diet-Derived Circulating Antioxidants and Risk of Coronary Heart Disease: A Mendelian Randomization Study

BackgroundPreviously, observational studies have identified associations between higher levels of dietary-derived antioxidants and lower risk of coronary heart disease (CHD), whereas randomized clinical trials showed no reduction in CHD risk following antioxidant supplementation. ObjectivesThe purpose of this study was to investigate possible causal associations between dietary-derived circulating antioxidants and primary CHD risk using 2-sample Mendelian randomization (MR). MethodsSingle-nucleotide polymorphisms for circulating antioxidants (vitamins E and C, retinol, β-carotene, and lycopene), assessed as absolute levels and metabolites, were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene-CHD associations were obtained from 3 databases: the CARDIoGRAMplusC4D consortium (60,801 cases; 123,504 control subjects), UK Biobank (25,306 cases; 462,011 control subjects), and FinnGen study (7,123 cases; 89,376 control subjects). For each exposure, MR analyses were performed per outcome database and were subsequently meta-analyzed. ResultsAmong an analytic sample of 768,121 individuals (93,230 cases), genetically predicted circulating antioxidants were not causally associated with CHD risk. For absolute antioxidants, the odds ratio for CHD ranged between 0.94 (95% confidence interval [CI]: 0.63 to 1.41) for retinol and 1.03 (95% CI: 0.97 to 1.10) for β-carotene per unit increase in ln-transformed antioxidant values. For metabolites, the odds ratio ranged between 0.93 (95% CI: 0.82 to 1.06) for γ-tocopherol and 1.01 (95% CI: 0.95 to 1.08) for ascorbate per 10-fold increase in metabolite levels. ConclusionsEvidence from our study did not support a protective effect of genetic predisposition to high dietary-derived antioxidant levels on CHD risk. Therefore, it is unlikely that taking antioxidants to increase blood antioxidants levels will have a clinical benefit for the prevention of primary CHD.

Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis.

OBJECTIVEObservational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding.RESEARCH DESIGN AND METHODSUsing 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (251,420 women and 212,049 men). Weighted median, MR-Egger, MR-pleiotropy residual sum and outlier, and radial MR from summary-level analyses were used for pleiotropy assessment.RESULTSMR analyses showed that genetic risk of type 2 diabetes increased the odds of CHD for women (odds ratio 1.13 [95% CI 1.08–1.18] per 1-log unit increase in odds of type 2 diabetes) and men (1.21 [1.17–1.26] per 1-log unit increase in odds of type 2 diabetes). Sensitivity analyses showed some evidence of directional pleiotropy; however, results were similar after correction for outlier SNPs.CONCLUSIONSThis MR analysis supports a causal effect of genetic liability to type 2 diabetes on risk of CHD that is not stronger for women than men. Assuming a lack of bias, these findings suggest that the prevention and management of type 2 diabetes for CHD risk reduction is of equal priority in both sexes.

Explaining the increment in coronary heart disease mortality in Mexico between 2000 and 2012.

Mexico is still in the growing phase of the epidemic of coronary heart disease (CHD), with mortality increasing by 48% since 1980. However, no studies have analyzed the drivers of these trends. We aimed to model CHD deaths between 2000 and 2012 in Mexico and to quantify the proportion of the mortality change attributable to advances in medical treatments and to changes in population-wide cardiovascular risk factors. We performed a retrospective analysis using the previously validated IMPACT model to explain observed changes in CHD mortality in Mexican adults. The model integrates nationwide data at two-time points (2000 and 2012) to quantify the effects on CHD mortality attributable to changes in risk factors and therapeutic trends. From 2000 to 2012, CHD mortality rates increased by 33.8% in men and by 22.8% in women. The IMPACT model explained 71% of the CHD mortality increase. Most of the mortality increases could be attributed to increases in population risk factors, such as diabetes (43%), physical inactivity (28%) and total cholesterol (24%). Improvements in medical and surgical treatments together prevented or postponed 40.3% of deaths; 10% was attributable to improvements in secondary prevention treatments following MI, while 5.3% to community heart failure treatments. CHD mortality in Mexico is increasing due to adverse trends in major risk factors and suboptimal use of CHD treatments. Population-level interventions to reduce CHD risk factors are urgently needed, along with increased access and equitable distribution of therapies.

Abstract 15273: Estimating Coronary Heart Disease Risk and Treatment Benefit in Patients With Familial Hypercholesterolemia to Enable Shared Decision Making

Introduction: Current risk equations for coronary heart disease (CHD) do not take into account family history or cumulative exposure to LDL-C. We modified CHD risk equations for use in familial hypercholesterolemia (FH) patients and developed a decision aid (DA) for FH to facilitate shared decision making (SDM). Methods: Literature review, evidence synthesis and expert input were used to adapt the 30-year Framingham Risk Score (FRS) and 10-year ACC/AHA pooled cohort equations to calculate the CHD risk in individuals with FH aged 20-39 years and ≥40 years, respectively. Based on published data, estimated risk was multiplied by 2 for family history of early CHD or 3 in the presence of a pathogenic variant. Treatment benefit of lipid lowering was estimated based on the ‘cumulative exposure to LDL-C’ model ( JACC 2012; 60 ) using the following equations: Post-treatment 30-yr risk in those aged 20-39 years = Baseline Risk (FRS) x 0.54 delta LDL-C (mmol/L) Post-treatment 10-yr risk in those aged ≥40 years = Baseline Risk (ACC/AHA Pooled Cohort) x 0.72 delta LDL-C (mmol/L) To convey CHD risk and treatment benefit, we developed a DA using an iterative, patient-centered design process for use in FH encounters. Results: Using the DA, providers can discuss baseline CHD risk estimates, lipid lowering drug (LLD) options and the expected post-treatment risk reduction with FH patients. The estimated % LDL-C reduction for each LLD and the predicted risk reduction per mmol/L of LDL-C lowered were obtained from literature review. Lowering LDL-C by 1 mmol/L (39 mg/dL) was associated with a 28% CHD risk reduction over 10 years and a 46% reduction over 30 years ( Eur Heart J 2017; 38 ). We describe 2 examples of estimating CHD risk and treatment benefit in FH cases in Table 1 . Conclusion: We adapted CHD risk prediction equations to account for family history of CHD and presence of a pathogenic FH variant and designed a DA to convey personalized CHD risk estimates and treatment benefit to facilitate SDM with FH patients.

Association of small, dense LDL-cholesterol concentration and lipoprotein particle characteristics with coronary heart disease: A systematic review and meta-analysis.

The aim of this study was to systematically collate and appraise the available evidence regarding the associations between small, dense low-density lipoprotein (sdLDL) and incident coronary heart disease (CHD), focusing on cholesterol concentration (sdLDL-C) and sdLDL particle characteristics (presence, density, and size). Coronary heart disease (CHD) is the leading cause of death worldwide. Small, dense low-density lipoprotein (sdLDL) has been hypothesized to induce atherosclerosis and subsequent coronary heart disease (CHD). However, the etiological relevance of lipoprotein particle size (sdLDL) versus cholesterol content (sdLDL-C) remains unclear. PubMed, MEDLINE, Web of Science, and EMBASE were systematically searched for studies published before February 2020. CHD associations were based on quartile comparisons in eight studies of sdLDL-C and were based on binary categorization in fourteen studies of sdLDL particle size. Reported hazards ratios (HR) and odds ratios (OR) with 95% confidence interval (CI) were standardized and pooled using a random-effects meta-analysis model. Data were collated from 21 studies with a total of 30,628 subjects and 5,693 incident CHD events. The average age was 67 years, and 53% were men. Higher sdLDL and sdLDL-C levels were both significantly associated with higher risk of CHD. The pooled estimate for the high vs. low categorization of sdLDL was 1.36 (95% CI: 1.21, 1.52) and 1.07 (95% CI: 1.01, 1.12) for comparing the top quartiles versus the bottom of sdLDL-C. Several studies suggested a dose response relationship. The findings show a positive association between sdLDL or sdLDL-C levels and CHD, which is supported by an increasing body of genetic evidence in favor of its causality as an etiological risk factor. Thus, the results support sdLDL and sdLDL-C as a risk marker, but further research is required to establish sdLDL or sdLDL-C as a potential therapeutic marker for incident CHD risk reduction.

The Role of the Gut Microbiota in Coronary Heart Disease.

This review focuses on recent evidence examining the role gut microbiota play in coronary heart disease. It also provides a succinct overview of current and future therapies targeting the gut microbiota for coronary heart disease risk reduction. A consensus has been reached that differences exist in the gut microbiotas of patients with coronary heart disease. Studies have shown that the gut microbiota is associated with obesity, diabetes, dyslipidemia, and hypertension, which are risk factors for coronary heart disease. The gut microbiota is involved in mediating basic metabolic processes, such as cholesterol metabolism, uric acid metabolism, oxidative stress, and inflammatory reactions, through its metabolites, which can induce the development of atherosclerosis and coronary heart disease. Interfering with the composition of gut microbiota, supplementing probiotics, and fecal donation are active areas of research to potentially prevent and treat coronary heart disease. Gut microbiota are causally associated with coronary heart disease. We analyzed the gut microbiota's effects on risk factors for coronary heart disease and studied the effects of gut microbiota metabolites on coronary heart disease. Gut microbiota is a potential target for preventing and treating coronary heart disease.

Prevalence and correlates of metabolic syndrome among rural women in Mysore, India

AimsMetabolic Syndrome (MetS) is a strong predictor of Coronary Heart Disease (CHD). Studies in urban India have found about one-third of Indians suffer from MetS. Less is known about the prevalence of MetS in rural areas, where 70% of the population reside. This study examined the prevalence of Metabolic Syndrome in a population of rural women in India. MethodsData were gathered in a community-based study of 500 rural and tribal women residing in the Mysore district, between the age of 30–59 years. The study used the WHO STEPS approach, in which information on demographics and behavioral risk factors were collected. Along with anthropometric measurements, blood pressure, blood glucose, lipids were measured. A harmonized definition of MetS recommended by International Diabetes Federation Task Force on Epidemiology and Prevention was used in this study. ResultsThree out of five study participants were found to have MetS (47.1%, n = 223). Of those, 56.5% met 3 of the 5 criteria, 32.2% met 4 criteria, and 11.2% met all 5 criteria. Among the entire sample, low HDL was the most prevalent criterion (88.4%), followed by elevated glucose (57.9%), elevated triglycerides (49.3%), elevated BP (41.5%), and increased waist circumference (15.3%). In this sample, women with METS were generally older (p < 0.001), housewives (p = 0.001), that consumed salty highly processed foods (p = 0.020) and had low physical activity (p = 0.015). ConclusionsThis study showed a high prevalence of MetS in rural women. There is a compelling need for interventions aimed at reducing CHD risk factors in this population.

The Relationship Between Vegetarian Diet and The Risk of Coronary Heart Disease

Background. Coronary heart disease (CHD) is a major cause of death in developed countries whereas most cases can be prevented by addressing behavioral risk factors, such as unhealthy diet. Vegetarian dietary patterns reduce CHD risk and mortality by 40%. The Framingham Heart Study on Hard CHD calculates a 10-year risk assessment with six predictors, two of which are lipid profile types. Aims. To discover the relationship between vegetarian diet and the risk of coronary heart disease, we did a cross-sectional analytical observation in North Jakarta using 30 healthy vegetarians and 30 healthy non-vegetarians aged of 20-34 years in 2010. Framingham Heart Study on Hard CHD 10-year risk assessments were done on both groups. Methods. Results were compared and analyzed using Mann-Whitney U and Spearman correlation tests. Results. Mann-Whitney U test showed significant differences on total cholesterol and total FHS risk points (p-value 0.000; pvalue 0.000). Spearman correlation analysis on total risk points confirms a moderate negative degree for vegetarian diet and CHD risk (r = -0.525, p-value 0.000). In conclusion, there is a significant relationship between vegetarian diet and a reduced risk of coronary heart disease in 20-34 years of age.

P5322Oxidized phospholipids on apolipoprotein B-100 among black US adults with and without PCSK9 loss-of-function variants

Abstract Background High oxidized phospholipid-apolipoprotein B-100 (OxPL-apoB) levels are associated with an increased risk for coronary heart disease (CHD). Genetic PCSK9 loss-of-function (LOF) variants result in life-long lower levels of LDL-C and lipoprotein(a) and reduced CHD risk, but the association with OxPL-apoB is unknown. Purpose To estimate the association between PCSK9 LOF variants and OxPL-apoB levels among black adults. Methods Genotyping for LOF variants (Y142X and C679X) was conducted for 10,196 black Reasons for Geographic And Racial Differences in Stroke study participants. OxPL-apoB was measured using antibody E06 for all participants with LOF variants (n=241) and randomly selected participants, matched at a 1:3 ratio, without LOF variants (n=723). Low OxPL-apoB was defined as the bottom quartile of the population distribution (&lt;1.6 nM). Prevalence ratios (PR) and 95% confidence intervals (CI) were calculated for the association between PCSK9 LOF variants and low OxPL-apoB levels adjusting for age, sex, and estimated glomerular filtration rate. Results Adults with versus without PCSK9 LOF variants had lower LDL-C and lipoprotein(a) and were less likely to be taking a statin. (Table) A higher proportion of adults with versus without PCSK9 LOF variants had low OxPL-apoB levels (30.3 vs 23.4, p=0.03). After adjustment for covariates, the PR of low OxPL-apoB was increased for participants with compared to without LOF variants (PR 1.31, 95% CI 1.00, 1.72). Characteristics of REGARDS participants PCSK9 loss-of-function variant p-value Yes (n=241) No (n=723) Age, years, mean (SD) 63.7 (9.2) 63.8 (8.6) 0.81 Female, % 61.4 60.6 0.82 Diabetes, % 34.4 27.4 0.04 LDL-C, mg/dL, mean (SD) 85 (32) 118 (37) &lt;0.001 Lp(a), nmol/L, median (25th, 75th percentile) 63.2 (30.4, 119.6) 80.4 (39.7, 138.4) 0.02 Statin use, % 13.3 30.4 &lt;0.001 OxPL-apoB &lt;1.6 nM, % 30.3 23.4 0.03 Abbreviations: LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein(a); LOF, loss-of-function; nM, nanomolar; OxPL-apoB, oxidized phospholipids on apolipoprotein B-100; PCSK9, proprotein convertase subtilisin/kexin type-9; REGARDS, REasons for Geographic And Racial Differences in Stroke; SD, standard deviation. Conclusion Among black adults, PCSK9 LOF variants were associated with lower OxPL-apoB levels. Acknowledgement/Funding Industry/academic collaboration between Amgen Inc., University of Alabama at Birmingham and the Icahn School of Medicine at Mt. Sinai; and U01NS041588

Tea consumption is associated with a reduced risk of coronary heart disease in female but not male populations in Guangzhou, China.

BACKGROUND/OBJECTIVESThe association between tea consumption and risk of coronary heart disease (CHD) remains controversial. This study aimed to determine whether tea consumption has an effect on CHD risk in Chinese adults.SUBJECTS/METHODSIn this hospital-based case-control study, 267 cases of CHD and 235 non-CHD controls were enrolled. Blood samples from all cases were examined. Cardiac function indices (left ventricular ejection fraction, left ventricular end-diastolic dimension, lactate dehydrogenase, and creatine kinase of the muscle or brain type), blood lipid index (high-density lipoprotein cholesterol), and blood coagulation function indices (fibrinogen and activated partial thromboplastin time) were recorded. Tea consumption of study participants was assessed by a specifically designed questionnaire. The baseline characteristics of the study populations were recorded, and CHD-related biomarkers were detected. Differences in baseline characteristics of the study participants were examined using t-tests for continuous variables and chi-squared tests for categorical variables. Unconditional logistic regression was used to measure the association between tea and CHD.RESULTSThere were significant differences in cardiac function indices, blood lipid index, and blood coagulation indices between CHD cases and controls (P < 0.05). We found tea consumption reduced CHD risk in female participants (adjusted odds ratio (OR) = 0.484, 95% CI: 0.242–0.968, P = 0.0403). Regarding the type of tea consumed, the risk of CHD was reduced in women who drank partially fermented tea (adjusted OR = 0.210, 95% CI: 0.084–0.522, P = 0.0008). Analytic results for the amount of tea consumed per unit time showed CHD risk was reduced in women who consumed 1–2 cups of tea per day (adjusted OR = 0.291, 95% CI: 0.131–0.643, P = 0.0023). A tea-drinking frequency of > 6 days/week was beneficial for CHD prevention (adjusted OR = 0.183, 95% CI: 0.049–0.679, P = 0.0112). When analyzed according to the duration of tea consumption, the risk of CHD was reduced in participants who had been drinking tea for 10–20 years (adjusted OR = 0.360, 95% CI: 0.137–0.946, P = 0.0382).CONCLUSIONSTea consumption is associated with a reduced risk of CHD in female but not male populations in Guangzhou.

Thai Tea Seed (Camellia oleifera) Oil Favorably Affects Plasma Lipid Responses in Hamsters Fed High‐Fat Diets

Coronary heart disease (CHD) is the leading cause of death worldwide. Dietary inclusion of monounsaturated fatty acids (MUFA) such as olive oil (OO) can reduce CHD risk. Tea seed oil (TSO) from Camellia oleifera grown in Thailand, with a MUFA content similar to OO, may be an alternative to OO when a higher cooking smoke point is desired. The lipid profiles, liver histology, and serum chemistries of hamsters fed high‐fat diets (TSO, OO, grape seed oil or butter; 14% by weight) are analyzed. After three weeks of feeding, TSO and OO groups have similar plasma low‐density lipoprotein cholesterol (LDL‐C), very‐low‐density lipoprotein cholesterol (VLDL‐C), triacylglycerols (TAG), high‐density lipoprotein cholesterol (HDL‐C), and total cholesterol (TC) levels. Moreover, TC/HDL‐C and LDL‐C/HDL‐ C ratios are also comparable. Similar to the OO group, the TSO group has significantly lower plasma LDL‐C, VLDL‐C, TAG, TC, and a lower TC/ HDL‐C ratio as compared to the butter group. Some minor liver pathological lesions commonly found in rodents fed high‐fat diets are observed. Thai TSO may be a healthy option for cooking, and clinical studies are warranted.Practical Applications: With its high smoking point, TSO is attractive to Asian consumers for their styles of cuisine. As it is produced locally, its price is cheaper than imported OO. This study demonstrates TSO's health benefits in lowering lipid profiles similar to OO. Based on this fact, this study supports Thai TSO cultivation in northern Thailand as a means of increasing rural villagers’ income.Hamsters are divided into five groups: tea seed oil, olive oil, grape seed oil, low fat, and butter. Tea seed oil favorably lowers plasma low‐density lipoprotein cholesterol (LDL‐C) in hamsters fed high‐fat diets.

Clinical Impact of 5Years of Liraglutide Treatment on Cardiovascular Risk Factors in Patients with Type 2 Diabetes Mellitus in a Real-Life Setting in Italy: An Observational Study.

IntroductionBased on existing data regarding the durability of liraglutide in type 2 diabetes, this study aimed to assess its long-term effectiveness at 5 years and its overall impact on cardiovascular (CV) risk.MethodsThis was a multicenter retrospective observational study. Liraglutide was used under routine clinical practice conditions. Changes from baseline to 60 months in HbA1c, fasting plasma glucose (FPG), body weight, blood pressure, and lipid profile were assessed. United Kingdom Prospective Diabetes Study (UKPDS) scores were calculated at baseline and after 60 months to assess changes in the estimated 5- and 10-year risk for fatal and nonfatal coronary heart disease (CHD) and fatal and nonfatal stroke.ResultsOverall, 103 patients (age 59.0 ± 7.9 years, diabetes duration 10.4 ± 6.8 years) were involved in the study. After 60 months, HbA1c levels were reduced by − 1.0 ± 1.2%, FPG levels by − 24.5 ± 43.4 mg/dl, body weight by − 5.3 ± 6.4 kg, systolic blood pressure by − 6.5 ± 18.5 mmHg, diastolic blood pressure by − 3.6 ± 11.8 mmHg, and total cholesterol by − 16.9 ± 37.4 mg/dl. The proportion of patients achieving HbA1c levels of < 7% increased from 12.7% to 39.8% (p = 0.02). Based on the UKPDS scores, statistically significant reductions in the 5- and 10-year risk of nonfatal CHD and fatal CHD were found, with no change in the 5- and 10-year risk of fatal and nonfatal stroke.ConclusionIn patients prolonging treatment with liraglutide for 5 years, the benefits in relation to metabolic control and CV risk factors are maintained. The UKPDS risk scores suggest that liraglutide is associated with a reduced CHD risk, but not with a reduced stroke risk.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0503-4) contains supplementary material, which is available to authorized users.

The High Density Lipoprotein Cholesterol Hypothesis Revisited

BACKGROUND: The strong inverse association of plasma levels of high-density lipoprotein cholesterol (HDL-C) with coronary heart disease (CHD) found in human epidemiological studies led to the development of the ‘HDL-C hypothesis’, which posits that intervention to raise HDL-C will result in reduced risk of CHD. However, recent evidence has raised doubts about the hypotheses that elevating HDL-C is necessarily therapeutic. Genetic variations that associate with altered HDL-C do not strongly associate with altered cardiovascular disease risk.CONTENT: HDL-mediated cholesterol efflux from macrophage foam cells or measurements of the flux of cholesterol from macrophages to the liver and feces seem to correlate better with atherosclerotic burden than with HDL-C levels. Thus, it may be time to modify the HDL-C hypothesis to the ‘HDL flux hypothesis’, where intervention to promote cholesterol efflux and reverse cholesterol transport will reduce CHD risk, regardless of whether it affects plasma HDL-C levels. A deeper understanding of the complex biology of HDL metabolism and its relationship to reverse cholesterol transport and atherothromobotic events is urgently needed. This might lead to biomarkers of HDL flux and functionality that are more informative than simple measurements of HDL-C levels.SUMMARY: It is now clear from recent clinical trial and genetic studies that some approaches to raising HDL-C levels may have no effect on CHD. This suggests the need to evaluate HDL-C-raising therapies in different clinical populations, as well as therapies targeted toward HDL flux and function rather than simply HDL-C elevation. Perhaps moving from a focus on the HDL-C hypothesis to a focus on the HDL flux hypothesis will permit a biologically based reassessment of the optimal therapeutic approach to targeting HDL for reduction in cardiovascular risk.KEYWORDS: reverse cholesterol transport, cholesterol efflux capacity, HDL dysfunction, HDL particle size, HDL lipidomics, HDL proteomics