Future Coronary Heart Disease Research Articles

RETINAL MICROVASCULAR CHANGES AND RISK OF CORONARY HEART DISEASE: A Systematic Review and Meta-Analysis.

To quantify associations between various retinal microvascular changes and the risk of the development of coronary heart disease (CHD). PubMed, Embase, Web of Science, and Cochrane Library databases were searched for cohort studies on the association between retinal microvascular changes and incident CHD up to July 31, 2023. The summary risk estimates were estimated using the random-effects model. Subgroup and sensitivity analyses were performed to investigate the potential source of heterogeneity. The authors identified 21 studies that met the inclusion criteria of this meta-analysis through database searching. This study yielded significant associations between retinal microvascular changes, including arteriolar narrowing, venular widening, vessel occlusion, and other retinal vascular signs, and the risk of CHD, with pooled adjusted hazard ratios of 1.20 (95% confidence interval: 1.13-1.27). In sex- and age-stratified analyses, retinal microvascular changes were associated with a greater risk of developing CHD in female patients and younger adults. A range of retinal microvascular changes was associated with the risk of CHD, particularly in female patients and younger ages. The results of this study support the concept that retinal microvascular abnormalities may be markers for future CHD. Noninvasive retinal microvascular assessments may be helpful in screening patients with increased CHD risk.

C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.

Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population. Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L). Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024). While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.

Lipidomics identified novel cholesterol-independent predictors for risk of incident coronary heart disease: Mediation of risk from diabetes and aggravation of risk by ambient air pollution

IntroductionPrevious lipidomics studies have identified various lipid predictors for cardiovascular risk, however, with limited predictive increment, sometimes using too many predictor variables at the expense of practical efficiency. ObjectivesTo search for lipid predictors of future coronary heart disease (CHD) with stronger predictive power and efficiency to guide primary intervention. MethodsWe conducted a prospective nested case-control study involving 1,621 incident CHD cases and 1:1 matched controls. Lipid profiling of 161 lipid species for baseline fasting plasma was performed by liquid chromatography-mass spectrometry. ResultsIn search of CHD predictors, seven lipids were selected by elastic-net regression during over 90% of 1000 cross-validation repetitions, and the derived composite lipid score showed an adjusted odds ratio of 3.75 (95% confidence interval: 3.15, 4.46) per standard deviation increase. Addition of the lipid score into traditional risk model increased c-statistic to 0.736 by an increment of 0.077 (0.063, 0.092). From the seven lipids, we found mediation of CHD risk from baseline diabetes through sphingomyelin (SM) 41:1b with a considerable mediation proportion of 36.97% (P < 0.05). We further found that the positive associations of phosphatidylcholine (PC) 36:0a, SM 41:1b, lysophosphatidylcholine (LPC) 18:0 and LPC 20:3 were more pronounced among participants with higher exposure to fine particulate matter or its certain components, also to ozone for LPC 18:0 and LPC 20:3, while the negative association of cholesteryl ester (CE) 18:2 was attenuated with higher black carbon exposure (P < 0.05). ConclusionWe identified seven lipid species with greatest predictive increment so-far achieved for incident CHD, and also found novel biomarkers for CHD risk stratification among individuals with diabetes or heavy air pollution exposure.

Can the association between LDL-Cholesterol and incident coronary heart disease (CHD) be modulated by concomitant Lp(a) levels in the general population?

Abstract Background LDL-cholesterol (LDL-C), quantified by conventional methods, also includes the choles-terol attributable to Lipoprotein (a) (Lp(a)-C) due to their overlapping densities. The clinical relevance of this is still poorly investigated, since current attempts to estimate a true LDL-C (i.e. a LDL-C without its Lp(a)-C content, so called LDL-C-Lp(a)corr) remain challenging. Aims The aims of the present analysis were 1) to compare the association between LDL-C and LDL-C-Lp(a)corr with incident coronary heart disease (CHD) in the general population; 2) to determine the prognostic ability of LDL-C for future CHD events depending on concomitant Lp(a) levels. Methods Data from 68,748 subjects from eight European prospective population-based cohorts, who were free of CHD at baseline were used. LDL-C-Lp(a)corr was calculated as "LDL-C - Lp(a)-C", where Lp(a)-C was estimated as being 30% of the Lp(a) total mass. Fine and Gray competing risk-adjusted models were calculated for the association between LDL-C and LDL-C-Lp(a)corr (in quintiles (Q) with Q1 as REF) and future CHD events in the total study sample, as well as for LDL-C only after categorization of the study population according to Lp(a) mass (&amp;lt;90th percentile (pctl.) (43,5 mg/dL) (n=61,861) and ≥90th pctl. (n=6,887)). Results Similar risk estimates for incident CHD were found for LDL-C and LDL-C-Lp(a)corr with sHRs of 2.69 (95% CI 2.30-3.15) and 2.49 (95% CI 2.13-2.90), respectively (both p&amp;lt;0.001, comparing Q5 vs Q1; fully-adjusted models, including traditional cardiovascular risk factors and hsCRP). Categorization of the study sample according to Lp(a) mass revealed that the association between LDL-C and incident CHD was potentiated by higher Lp(a) mass (≥90th pctl) resulting in a sHR of 4.36 (95% CI 2.05-9.23; p&amp;lt;0.001 for Q5 vs Q1; fully-adjusted model), which was approximately x1.5 higher than the risk estimate found in the total study sample (i.e. without categorization for Lp(a) mass). In contrast, in subjects with Lp(a) mass &amp;lt;90th pctl. sHR for future CHD events was found to be 2.56 (95% CI 2.18-3.02) (for Q5 vs Q1 of LDL-C distribution; fully-adjusted model), being almost identical to the sHR obtained within the overall cohort (p for interaction between the categories of Lp(a) was 0.42). Conclusion Within the present analysis, correction of LDL-C for its Lp(a)-C content did not provide any meaningful additional information on CHD-risk estimation in the general population, thereby not confirming a clinically relevant value of LDL-C-Lp(a)corr. On the other hand, a simple categorization of Lp(a) mass with respect to high (≥90th pctl.) vs low (&amp;lt;90th pctl.) values demonstrated that Lp(a) significantly modulates LDL-C-related risk for future CHD only at higher levels. So, for the vast majority of subjects (&amp;lt;90th pctl. of Lp(a) distribution), no correction of LDL-C for its Lp(a)-C content is required.

Genetics and Ischemic Heart Disease: Should We Opt for Genetic Testing for Primary Prevention?

Cardiovascular diseases (CVD) are a prevalent health concern within the general population of Pakistan, where the average lifespan is notably lower than the global average, with men typically living to 67 years and women to 69 years. According to the 2019 Global Burden of Disease study, Pakistan had an estimated age-standardized incidence rate of CVD at 918.18 per 100,000 (compared to the global rate of 684.33 per 100,000), along with an age-standardized death rate of 357.88 per 100,000 (globally, this rate is 239.85 per 100,000).1 Coronary heart disease (CHD), as revealed by the Framingham Heart Study focusing on individuals aged 40 to 94 without prior heart disease, displayed a lifetime risk of 49% for men and 32% for women when reaching the age of 40.2 There has been a declining trend in death rates in the United States attributed to CVD, CHD, and stroke since 1975. Data from 2000 to 2008 also indicate a decline in CHD mortality.3 Worryingly, the World Health Organization (WHO) reports a concerning rise in CHD-related fatalities in Pakistan. In 2020, 240,720 individuals died due to CHD, accounting for 16.49% of all deaths. This highlights an escalating trend of CHD-related mortality in Pakistan. It's important to note that most individuals presenting with cardiac events have one or more established or borderline risk factors aside from age and gender.4-6 While some essential risk factors are discernible, others may remain elusive. The screening of these risk factors and the evidence for targeted therapeutic interventions are still emerging and require further exploration.7 The starting point for assessing CVD risk factors is variables used to predict major cardiovascular events. These include age, sex, blood pressure, cholesterol levels, diabetes mellitus, and smoking status. Although risk assessment tools like the Pooled Cohort Equation in 2014 and Astro-CHARM have been developed, they have yet to provide satisfactory assessments for potential new CVD risk factors.8 CHD is recognized as a multifactorial disorder resulting from genetic and environmental factors interplay. Environmental risk factors have been identified in approximately 80% of CHD cases.9 Several risk scores, such as the Framingham Risk Score, PROCAM, Reynolds Risk Score, and QRISK 2, have been proposed to guide the use of statins in high-risk groups.10-14 Yet, these risk scores often lack precision and may either overestimate or underestimate future CHD events.15,16 The variation in disease susceptibility among individuals with similar environmental factors and conventional coronary artery disease risk factors (CRFs) may be attributed to genetic variations.17 Genetic analysis can potentially enhance risk discrimination beyond the consideration of CRFs alone. Family history of heart disease, accounting for more than 40% of risk estimation, has long been considered a part of CRFs.18 Candidate gene studies have been conducted to identify common variants in genes associated with disease pathways.19 Single-nucleotide polymorphisms (SNPs) have been employed as markers of genetic diversity. Among these SNPs, those located on the 9p21 locus have shown the strongest association with CHD risk to date.20,21 However, despite the clear link between these variants and incident CHD, 9p21 locus SNPs have not definitively improved the prediction or classification of CHD risk compared to traditional risk factors.22-24 It is important to note that most genetic studies on CHD have predominantly focused on European/Caucasian populations, and their applicability to the South Asian population, including Pakistan, requires further investigation.25,26 In this context, the Pakistani population, much like other Asian countries, is underrepresented in genetic research on CHD. Shahid SU et al. did some work in this respect,27 showing 21 SNPs risk score for genetic risk analysis in the Pakistani population. In conclusion, while different risk assessment tools have been developed for the Pakistani population aged 40 years and above, there is an urgent need to expand cardiac risk evaluation by identifying genetic markers related to CHD, particularly in the younger population. This will be crucial for advancing our understanding of CHD risk factors and developing more effective prevention and intervention strategies.

Forecasting the mortality burden of coronary heart disease and stroke in Germany: National trends and regional inequalities

BackgroundThe decline of cardiovascular disease (CVD) mortality has slowed in many countries, including Germany. We examined the implications of this trend for future coronary heart disease (CHD) and stroke mortality in Germany considering persistent mortality inequalities between former East and West Germany. MethodsWe retrieved demographic and mortality data from 1991 to 2019 from the German Federal Statistical Office. Using a Bayesian age-period-cohort framework, we projected CHD and stroke mortality from 2019 to 2035, stratified by sex and German region. We decomposed annual changes in deaths into three components (mortality rates, population age structure and population size) and assessed regional inequalities with age-sex-standardized mortality ratios. ResultsWe confirmed that declines of CVD mortality rates in Germany will likely stagnate. From 2019 to 2035, we projected fewer annual CHD deaths (114,600 to 103,500 [95%-credible interval: 81,700; 134,000]) and an increase in stroke deaths (51,300 to 53,700 [41,400; 72,000]). Decomposing past and projected mortality, we showed that population ageing was and is offset by declining mortality rates. This likely reverses after 2030 leading to increased CVD deaths thereafter. Inequalities between East and West declined substantially since 1991 and are projected to stabilize for CHD but narrow for stroke. ConclusionsCVD deaths in Germany likely keep declining until 2030, but may increase thereafter due to population ageing if the reduction in mortality rates slows further. East-West mortality inequalities for CHD remain stable but may converge for stroke. Underlying risk factor trends need to be monitored and addressed by public health policy.

Association of Circulating Matrix Metalloproteinase-9 and the Risk of Coronary Heart Disease in Young Smokers

Introduction: Smoking causes cardiovascular risk which may alter the stability between the production and degradation of the extracellular matrix. Matrix metalloproteinase-9 (MMP-9) is a zinc-containing endopeptidase that degrades the extracellular matrix and plays a vital role in tissue remodeling. As a result, elevated serum MMP-9 levels produced by smoking, particularly at young age, raise the risk of future CHD. So this study aims to find out the possible relationship between circulating MMP-9 and the risk of cardiovascular disease in young smokers. Methods: The study was conducted on smokers with CHD subjects attending cardiology and medicine OP of the SRM Medical College Hospital and research center Tamil Nadu, India. The study group was divided into three groups. Group 1 includes 120 healthy controls as nonsmokers, Group 2 includes 120 smokers with Coronary heart disease (CHD), and Group 3 includes 120 smokers with diabetes and CHD subjects in the age group of 20-55 years. Serum MMP-9, hs-CRP, and APO-E levels were measured using the ELISA method and the lipid level was measured enzymatically using AU480 automatic analyzer (back man coulter). Results: The mean serum MMP-9, hs-CRP, and APO-E levels were significantly higher in both groups (p&lt;0.05) when compared to controls. The study also shows a significant positive association between MMP-9 with hs-CRP, APO-E, smoking burden, and smoking intensity. Conclusion: The study concludes a significant association exists between cigarette smoking with MMP-9 and also relative exposure to circulating inflammation markers plays a potential role in the pathogenesis of CHD.

Serum High-Sensitivity Cardiac Troponin T as an Independent Predictor for Incident Coronary Heart Disease in the Japanese General Population: The Circulatory Risk in Communities Study (CIRCS).

Epidemiological evidence is extremely limited about high-sensitivity cardiac troponin T (hs-cTnT) and future coronary heart disease (CHD) events for the general population in countries with low mortality from CHD. Therefore, we investigated the association between hs-cTnT levels and the risk of incident CHD using a nested case-control study in a large Japanese cohort study. The participants were residents of four Japanese communities in the Circulatory Risk in Communities Study (CIRCS). We obtained 120 cases (81 men and 39 women, aged 38-86 years at baseline) of first incident CHD and 240 controls matched by age, sex, communities, and blood sampling term. Serum hs-cTnT levels were measured using an electrochemiluminescence immunoassay with stored sera collected between 2001 and 2011. The median period between sampling at survey and CHD incidence was 2.0 (interquartile range, 0.9-3.7) years. After adjusting for conventional risk factors, the multivariable odds ratios (ORs) of CHD were calculated using conditional logistic regression analyses. hs-cTnT ranged from ≤ 3 (assay detection limit) to 155 ng/L. Compared with the lowest quartile of hs-cTnT, multivariable ORs (95% confidence intervals) of CHD for the second, third, and highest quartiles were 1.30 (0.57-2.95), 2.48 (1.09-5.64), and 3.01 (1.27-7.12), respectively. Similar associations were observed after adjusting for estimated glomerular filtration, or after excluding matched groups, including people with chronic kidney disease. Serum hs-cTnT could predict CHD in the Japanese general population. These findings implicate a benefit from monitoring hs-cTnT to predict CHD even among populations in countries with low mortality from CHD.

Validation of low-density lipoprotein cholesterol equations in pediatric population.

Several studies have shown a high prevalence of dyslipidemia in children. Since childhood lipid concentrations continue into adulthood, recognition of lipid abnormalities in the early period is crucial to prevent the development of future coronary heart disease (CHD). Low density lipoprotein cholesterol (LDL-C) is one of the most used parameters in the initiation and follow-up of treatment in patients with dyslipidemia. It is a well known fact that LDL-C lowering therapy reduces the risk of future CHD. Therefore, accurate determination of the LDL-C levels is so important for the management of lipid abnormalities. This study aimed to validate different LDL-C estimating equations in the Turkish population, composed of children and adolescents. A total of 3,908 children below 18 years old at Sivas Cumhuriyet University Hospital (Sivas, Turkey) were included in this study. LDL-C was directly measured by direct homogeneous assays, i.e., Roche, Beckman, Siemens and estimated by Friedewald's, Martin/Hopkins', extended Martin-Hopkins' and Sampson's formulas. The concordances between the estimations obtained by the formulas and the direct measurements were evaluated both overall and separately for the LDL-C, triglycerides (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) sublevels. Linear regression analysis was performed and residual error plots were generated between each estimation and direct measurement method. Coefficient of determination (R 2) and mean absolute deviations were also evaluated. The overall concordance of Friedewald, Sampson, Martin-Hopkins and the extended Martin-Hopkins formula were 64.6%, 69.9%, 69.4%, and 84.3% for the Roche direct assay, 69.8%, 71.6%, 73.6% and 80.4% for the Siemens direct assay, 66.5%, 68.8%, 68.9% and 82.1% for the Beckman direct assay, respectively. The extended Martin-Hopkins formula had the highest concordance coefficient in both overall and all sublevels of LDL-C, non-HDL-C, and TG. When estimating the LDL-C categories, the highest underestimation degrees were obtained with the Friedewald formula. Our analysis, conducted in a large pediatric population, showed that the extended Martin-Hopkins equation gives more reliable results in estimation of LDL-C compared to other equations.

Projections of future coronary heart disease and stroke mortality in Japan until 2040: a Bayesian age-period-cohort analysis

We aimed to estimate the future burden of coronary heart disease (CHD) and stroke mortalities by sex and all 47 prefectures of Japan until 2040 while accounting for effects of age, period, and cohort and integrating them to be at the national level to account for regional differences among prefectures. We estimated future CHD and stroke mortality projections, developing Bayesian age-period-cohort (BAPC) models in population and the number of CHD and stroke by age, sex, and all 47 prefectures observed from 1995 to 2019; then applying these to official future population estimates until 2040. The present participants were all men and women aged over 30 years and were residents of Japan. In the BAPC models, the predicted number of national-level cardiovascular deaths from 2020 to 2040 would decrease (39,600 [95% credible interval: 32,200-47,900] to 36,200 [21,500-58,900] CHD deaths in men, and 27,400 [22,000-34,000] to 23,600 [12,700-43,800] in women; and 50,400 [41,900-60,200] to 40,800 [25,200-67,800] stroke deaths in men, and 52,200 [43,100-62,800] to 47,400 [26,800-87,200] in women). After adjusting these factors, future CHD and stroke deaths will decline until 2040at the national level and in most prefectures. This research was supported by the Intramural Research Fund of Cardiovascular Diseases of the National Cerebral and Cardiovascular Center (21-1-6, 21-6-8), JSPS KAKENHI Grant Number JP22K17821, and the Ministry of Health, Labour and Welfare Comprehensive Research on Life-Style Related (Diseases Cardiovascular Diseases and Diabetes Mellitus Program), Grant Number 22FA1015.

Abstract 13386: The Association of High Polygenic Risk With Future Coronary Heart Disease Events Diminishes Later in Life

Introduction: Polygenic risk scores (PRS) for coronary heart disease (CHD) are associated with incident CHD events. We assessed whether the strength of this association differs over the life course. Methods: We studied 7,958 genotyped participants of European-ancestry without CHD enrolled in the Atherosclerosis Risk in Communities Study (ARIC). Participants were 45-64 years old at the baseline visit occurring 1987-89 with follow up available through 2015. A genome-wide PRS for CHD composed of 1.7 million variants was computed for each participant. Incident CHD was defined as clinically adjudicated myocardial infarction including silent infarction, coronary revascularization, or fatal coronary event. An extended Cox model was constructed with age as the model time scale. The association of PRS with incident CHD was assumed to be log-linear and further modeled as a function of age assuming differing piecewise constant effect sizes across the intervals ≤55, 55-65, 65-80, and ≥80 years. The regression model also included the following covariates: sex, systolic blood pressure, total and HDL cholesterol, history of diabetes, antihypertensive medication use, and smoking status. Results: In the ARIC cohort (median enrollment age 54, interquartile range [IQR] 49-59, female 52%), over a median of 24.5 years (IQR 14.4-28.1), there were 1,872 incident CHD events. In comparison to average polygenic risk for CHD (50th percentile of PRS distribution), harboring high polygenic risk (95th percentile) was associated with a 2.9-fold increased risk of incident CHD (95% CI 2.12-3.95) up to age 55 years, independent of conventional risk factors. The strength of association was attenuated later in life (Hazard ratio, age 55-65, 2.5 [2.14-2.84]; age 65-80, 1.87 [1.68-2.07]; age ≥80, 1.78 [1.38-2.31]) Conclusions: A genome-wide PRS for CHD is more strongly associated with incident coronary events at younger age. The strength of association declined later in life while remaining significant. The age-dependent association of PRS with CHD may need to be accounted for in risk prediction models.

C-reactive protein as a possible modifier of Lipoprotein(a)-related risk for coronary heart disease in Europe: results from the BiomarCARE project

Abstract Background Lipoprotein(a) (Lp(a)) represents a unique proatherogenic lipoprotein with potent pro-thrombotic and pro-inflammatory properties. Recent studies demonstrated that Lp(a)-associated risk for cardiovascular disease (CVD) was significantly increased only in individuals with a high inflammatory burden (i.e. hsCRP levels &amp;gt;2 mg/L). However, these results have been either based on a post-hoc analysis in a highly selected study population with a high/very high CVD risk, or conducted within a multi-ethnic population with significant variation in Lp(a) levels. Purpose The main aim was to investigate whether hsCRP concentration modulates the predictive value of Lp(a) for coronary heart disease (CHD) events in the general population across Europe. Methods Data of 87,760 participants from 10 European prospective population-based cohorts, participating in the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, were used for the present analysis (79,958 subjects without and 7,189 individuals with established CHD at baseline (primary/secondary prevention cohorts, respectively)). All Lp(a) measurements were performed in the central BiomarCaRE laboratory. Fine and Gray competing risk-adjusted models stratified by study cohort were calculated to assess the association between Lp(a) levels and future CHD events stratified according to hsCRP levels (&amp;lt;1 mg/l, ≥1–&amp;lt;2 mg/l and ≥2 mg/l). Results During a median follow-up of 11.3 years, 4,928 events occurred in the CHD-free subpopulation and 1,772 events occurred in the CHD subpopulation. In the primary prevention cohort, increased Lp(a) was significantly associated with future CHD events irrespective of hsCRP: Hazard ratios (HRs) for future CHD events (top vs bottom quintile (Q) of Lp(a) distribution) were 1.46 (95% CI: 1.21–1.78; p&amp;lt;0.001) in those having a hsCRP concentration &amp;lt;1 mg/l; 1.32 (95% CI: 1.09–1.61; p=0.0052) for a hsCRP group of ≥1-&amp;lt;2 mg/l and 1.40 (95% CI: 1.22–1.61; p&amp;lt;0.001) in subjects with a hsCRP concentration ≥2 mg/l, after multivariable adjustment for traditional CV risk factors including LDL-Ccorr and lipid-lowering medication. In contrast, in the secondary prevention, we found no association between increased Lp(a) levels and CHD events in individuals with a very low inflammatory burden (HR for hsCRP &amp;lt;1 mg/l 0.92 (95% CI 0.63–1.34), p=0.66, Q5 vs Q1)), whereas the association was significant among subjects with a hsCRP concentration ≥1 mg/l (HRs: 1.43 (95% CI: 1.01–2.03; p=0.045) for hsCRP group ≥1-&amp;lt;2 mg/l and 1.35 (95% CI: 1.07–1.71; p=0.013) for hsCRP group ≥2 mg/l (both for Q5 vs Q1)). Conclusion In a primary prevention setting, Lp(a) was associated with incident CHD irrespective of the inflammatory burden. In contrast, among subjects with known CHD, the association of Lp(a) and future CHD events was only present in those with hsCRP levels &amp;gt;1 mg/l. These findings might guide target population selection for upcoming Lp(a)-targeting compounds. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by the 7th Framework Programme Collaborative Project (grant agreement no. HEALTH-F2-2011-278913). The MORGAM Project has received funding from EU projects MORGAM (Biomed, BMH4-CT98-3183), GenomEUtwin (Fifth Framework Programme FP5, QLG2-CT-2002-01254), ENGAGE (FP7, HEALTH-F4-2007-201413), CHANCES (FP7, HEALTH-F3-2010-242244), BiomarCaRE (FP7, HEALTH-F2-2011-278913), euCanSHare (Horizon 2020, No. 825903) and AFFECT-EU (Horizon 2020, No. 847770); and Medical Research Council, London (G0601463, No. 80983: Biomarkers in the MORGAM Populations).

The Effect of Spirulina on Anxiety in Patients with Hypertension: A Randomized Triple-Blind Placebo-Controlled Clinical Trial

Background: High blood pressure, coronary heart disease (CHD), and anxiety ailments entirely lead to many illness in patients and impose expenses on the health care system. Anxiety can significantly predict future CHD consequences. Spirulina is a known antioxidant that has a role in anxiety. The hypothesis was that Spirulina could alleviate anxiety and positively affect hypertension and its consequences. Nonetheless, there are scarce recently developed investigations on assessing the effect of consuming Spirulina on anxiety in human beings. Methods: The present study assessed the effect of Spirulina on anxiety in 48 Iranian patients with hypertension (female and male) aged 24–65 years in a randomized triple-blind, placebo-controlled clinical trial. The patients were given either 2 g Spirulina in the form of spirulina-fortified dressing or placebo. Anxiety levels were evaluated for each patient before and after eight weeks following consumption products with the Beck Anxiety Inventory. Results: Forty-one participants completed the intervention. At the baseline, there was no significant difference in anxiety levels between groups, and they also had the same levels of stress based on the Holmes-Rahe questionnaire. The results showed no significant difference in the level of anxiety between groups after the intervention (P = 0.93). Conclusion: Although no positive results were seen in this study, this novel issue has a potential for further investigations to make comprehensive decisions.

Usefulness of Novel Atherogenic Lipid Indices for the Evaluation of Metabolic Status Leading to Coronary Heart Disease in a Real-World Survey of the Japanese Population.

We evaluated the usefulness of two novel cholesterol-triglyceride subgroup (CTS) indices, CTSqlt and CTSqnt, that potentially reflect the metabolic status regarding risk of coronary heart disease (CHD) using a retrospective longitudinal study of the Japanese general population. We recruited 12,373 individuals from the annual users of our healthcare center. Among them, the first onset of CHD was recorded in 131 individuals between April 2014 and March 2020. The multivariate Cox proportional hazards regression analyses for all normalized lipid indices revealed that the CTSqnt index showed a comparable hazard ratio for the CHD outcome to non-high-density lipoprotein cholesterol (nonHDL-c) and triglycerides. The HR of the CTSqlt index was significantly lower than for CTSqnt, but still comparable to that for low-density lipoprotein cholesterol (LDL-c). In comparison with the other indices, CTSqlt is more sensitive to risk increment while the index value increases. Linear regression analyses for the CTS indices and previously known lipid indices suggest that the CTSqnt and CTSqlt indices reflect the quantity of atherogenic lipoproteins and particle size (quality) of smaller and denser LDLs, respectively. Furthermore, the CTSqnt/HDL-c index can be used as a comprehensive risk indicator that may represent the status of lipid metabolism determined by the CTSqlt and CTSqnt indices and thus may be useful for screening. The CTS indices can be used to evaluate the metabolic status of individuals, which may increase the risk of future CHD.

What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling

Background and aimsFamilial hypercholesterolemia (FH) is a genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary heart disease (CHD). Cholesterol-lowering therapy (statins) reduces CHD risk, but have been available only in the last 25 years, thus, elderly FH patients have been exposed to elevated LDL-C levels most of their life. Surprisingly, some of these have never experienced any CHD event, raising the question whether they present CHD resistant characteristics.Identifying possible cardioprotective biomarkers could contribute to future CHD preventive treatment, therefore, we aimed to identify metabolic markers in event-free elderly FH subjects. Methods and resultsWe used a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform to quantify a large number of metabolites in serum samples from 83 FH patients ≥65 years, and analyze differences between subjects with (n = 39) and without (n = 44) CHD.Mean age was 70 years in both groups (57% and 38% female in the event-free group and CHD group, respectively). The event-free group had significantly higher levels of large and extra-large high-density lipoprotein (HDL) particles, and higher concentration of Apolipoprotein A1 (ApoA1) and cholesterol in HDL and HDL2 particles, compared to the CHD group (p ≤ 0.05 for all). ConclusionCHD resistant elderly FH patients have higher levels of large HDL particles. The mechanisms behind the event-free survival among these patients remain unclear; hence, a deeper understanding of the metabolic profile in event-free elderly FH subjects may lead to development of novel preventive therapies.

Abstract P179: The Association Of A Genetic Risk Score With Prevalent Coronary Heart Disease In The Hispanic Community Health Study/Study Of Latinos (HCHS/SOL)

Background: Coronary heart disease (CHD) is one of the leading causes of death for the Hispanic/Latino population living in the United States (US). One way to reduce the burden of CHD is to target therapy and primary prevention in high-risk groups. Towards this end, a genetic risk score (GRS) constructed from 71 single-nucleotide polymorphisms (SNPs) has been used in populations of European ancestry to identify those at higher risk for CHD events and who would benefit most from statin therapy. Objectives: The purpose of this study is to evaluate a 71-SNP GRS with prevalent CHD in the HCHS/SOL cohort. Methods: The HCHS/SOL is a prospective, multi-center, population-based study that enrolled 16,415 Hispanic/Latino adults aged 18-74 years from four US communities in 2008-2011. Prevalent CHD was defined as self-reported physician-diagnosed angina, myocardial infarction, bypass, angioplasty, stent placement or evidence of electrocardiographic abnormalities indicative of CHD. We leveraged genome-wide genotype data to assess the association between a 71-SNP GRS and prevalent CHD among 9030 HCHS/SOL participants with accessible genetic data. Multivariable logistic regression was used to derive odds ratios and 95% confidence intervals for the association between GRS and prevalent CHD, adjusted for sex, age, and the first 5 principal components and weighted to adjust for sampling probability and non-response. Stratified analysis was conducted to explore heterogeneity by Hispanic/Latino background group. Results: The 71-SNP GRS had a range of 43-87 risk alleles among participants. In multivariable logistic regression analyses, participants in the top quintile of the GRS had 1.42 (95% CI: 1.11, 1.82) higher odds of prevalent CHD than participants in the lower four quintiles combined. Stratified analyses showed stronger associations between the GRS and prevalent CHD by Hispanic/Latino background group, with the strongest associations observed among participants of Cuban (OR=1.86; 95%: 1.18-2.92) and Central American (OR=2.81; 95% CI: 1.28-6.17) backgrounds. Conclusion: Our findings show that a previously developed 71-SNP GRS is associated with prevalent CHD among Hispanic/Latino participants. These findings may have important implications for lessening future CHD health disparities among Hispanics/Latinos living in the US.

Carotid plaque is strongly associated with coronary artery calcium and predicts incident coronary heart disease in a population-based cohort

Background and aimsCoronary artery calcium (CAC) and carotid plaque are markers of atherosclerosis and predict future coronary heart disease (CHD) events. The aim of this study was to investigate associations between CAC and carotid plaque in asymptomatic individuals, also in relation to predicted CHD-risk and incident events. A secondary aim was to compare predictive value between CAC, carotid plaque, and total carotid plaque area (TPA) as predictors for future CHD-events. MethodsThe REFINE-Reykjavik study is prospective and population-based with CAC-scoring and carotid plaque ultrasound assessment, both presence and area. A total of 948 individuals without clinical CHD were included in the study. CAC scores were categorized into 0,1–100,101-300 and > 300, and carotid plaque into none, minimal and significant. Three models were applied adjusted for age, sex, and each of the Framingham risk score (FRS), local CHD risk score and established CHD risk factors. ResultsCombined carotid plaque- and CAC-presence was highly prevalent, 69.5% for males and 41.7% for females (54.5% overall). TPA outperformed base models in CHD prediction, resulting in statistically significant area under the receiver operator characteristic curve (AUC) increase ranging from 0.02 to 0.05. Most CHD-events in females occurred in individuals classified as low-risk with respect to traditional risk factors but with a gradient in observed risk across carotid plaque categories. ConclusionsCarotid plaque was strongly associated with the presence and extent of CAC in asymptomatic individuals in a population-based cohort. Carotid plaque predicts incident CHD events over risk scores and may be useful for refined risk prediction in females.

Simple Nutrient-Based Rules vs. a Nutritionally Rich Plant-Centered Diet in Prediction of Future Coronary Heart Disease and Stroke: Prospective Observational Study in the US.

To better understand nutrition paradigm shift from nutrients to foods and dietary patterns, we compared associations of a nutrient-based blood cholesterol-lowering diet vs. a food-based plant-centered diet with risk of coronary heart disease (CHD) and stroke. Participants were 4701 adults aged 18–30 years and free of cardiovascular disease at baseline, followed for clinical events from 1985 and 86 to 2018. A plant-centered diet was represented by higher A Priori Diet Quality Score (APDQS). A blood cholesterol-lowering diet was represented by lower Keys Score. Proportional hazards regression was used to calculate hazard ratios (HR). Higher APDQS showed a nutrient-dense composition that is low in saturated fat but high in fiber, vitamins and minerals. Keys Score and APDQS changes were each inversely associated with concurrent plasma low-density lipoprotein cholesterol (LDL-C) change. Over follow-up, 116 CHD and 80 stroke events occurred. LDL-C predicted CHD, but not stroke. APDQS, but not Keys Score, predicted lower risk of CHD and of stroke. Adjusted HRs (95% CIs) for each 1-SD higher APDQS were 0.73 (0.55–0.96) for CHD and 0.70 (0.50–0.99) for stroke. Neither low dietary fat nor low dietary carbohydrate predicted these events. Our findings support the ongoing shift in diet messages for cardiovascular prevention.

Prospective increases in depression symptoms and markers of inflammation increase coronary heart disease risk - The Whitehall II cohort study

ObjectiveStress, inflammation, and depression are associated to coronary heart disease (CHD). However, how these constructs collectively contribute to CHD incidence is not well understood. For the first time, this study explored the concurrent relationship between workplace stress, depression symptomology and levels of low-grade inflammation with future CHD incidence. MethodsData from the 5-year intervals at phase 5, 7, and 9 of the Whitehall II study (N = 8348, Mage = 56) provided measures of workplace stress, depression symptomology, inflammation (interleukin-6, C-reactive protein, fibrinogen), and CHD incidence. The proposed stress-inflammation-depression-CHD pathway was assessed with a longitudinal design incorporating a structural equation model (SEM) that measured if changes in stress, depression, and inflammation between phase 5 to phase 7 predicted first-time CHD events between phases 7 and 9. ResultsThe SEM empirically supported this proposed pathway and demonstrated excellent model fit, χ (72) = 3582.959, p < .001, CFI = 0.896, RMSEA = 0.076 (CI90 = 0.074, 0.079), while depression symptoms mediated the association between workplace stress and CHD incidence, B = 0.003 (CI90 = 0.001, 0.004). Further, survival analysis indicated that individuals with higher mean scores (across phases) of depression symptoms or fibrinogen levels were more likely to experience a first time CHD event. ConclusionsIncreases in depression symptoms and fibrinogen levels may be good indicators of future CHD morbidity among older employees. Future research is encouraged to monitor negative affective states and the potential use of biobehavioural options to reduce depression and inflammation that may mitigate CHD risk.

Hiding unhealthy heart outcomes in a low-fat diet trial: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial finds that postmenopausal women with established coronary heart disease were at increased risk of an adverse outcome if they consumed a low-fat ‘heart-healthy’ diet

The Women’s Health Initiative Randomized Controlled Dietary Modification Trial (WHIRCDMT) was designed to test whether the US Department of Agriculture’s 1977 Dietary Guidelines for Americans protects against coronary heart disease...