Increased Risk Of Coronary Heart Disease Research Articles

INFLA score: a novel inflammatory marker for assessing cardiometabolic disease risk in obese individuals

BackgroundThe low-grade inflammation score (INFLA-score) is a composite index that assesses chronic inflammatory status using multiple inflammatory markers. However, its correlation with cardiometabolic diseases (CMDs) in obese populations remains unclear.MethodsWe conducted a prospective cohort study involving 79,160 participants with obesity (BMI ≥ 30 kg/m2) from the UK Biobank. The INFLA-score was calculated based on high-sensitivity C-reactive protein, leukocyte count, platelet count and granulocyte/lymphocyte ratio. We employed Kaplan–Meier survival curves, multivariable Cox regression, restricted cubic splines and accelerated time-to-failure models to analyse the association between the INFLA-score and CMDs risk, including coronary heart disease (CAD), stroke and type 2 diabetes mellitus (T2DM).ResultsOver a median follow-up of 161.41 months, we recorded 14,903 CMDs events, comprising 7184 CAD cases, 1914 strokes and 7924 T2DM cases. Cox regression analysis revealed that each unit increase in the INFLA-score corresponded to a 1.5%, 1.1%, 1.2% and 2.4% increase CMDs risk (HR: 1.015, 95% CI 1.013–1.018), CAD risk (HR: 1.011, 95% CI 1.007–1.015), stroke risk (HR: 1.012, 95% CI 1.004–1.020) and T2DM risk (HR: 1.024, 95% CI 1.020–1.028), respectively. Restricted cubic spline analysis indicated a non-linear relationship between cumulative INFLA-score and CMDs risk (P = 0.044). Subgroup analysis revealed interactions between sex, age, history of lipid-lowering drug use, and INFLA-score regarding CMDs risk. Sensitivity analysis corroborated the main findings.ConclusionOur findings strongly support the close association between INFLA-score and CMDs risk, particularly notable in women, those aged < 55, and individuals with a history of lipid-lowering drug use. These findings offer new insights into the role of inflammation in obesity-related CMDs, suggesting potential applications for prevention and identification of high-risk populations.

INFLA score: a novel inflammatory marker for assessing cardiometabolic disease risk in obese individuals

BackgroundThe low-grade inflammation score (INFLA-score) is a composite index that assesses chronic inflammatory status using multiple inflammatory markers. However, its correlation with cardiometabolic diseases (CMDs) in obese populations remains unclear.MethodsWe conducted a prospective cohort study involving 79,160 participants with obesity (BMI ≥ 30 kg/m2) from the UK Biobank. The INFLA-score was calculated based on high-sensitivity C-reactive protein, leukocyte count, platelet count and granulocyte/lymphocyte ratio. We employed Kaplan–Meier survival curves, multivariable Cox regression, restricted cubic splines and accelerated time-to-failure models to analyse the association between the INFLA-score and CMDs risk, including coronary heart disease (CAD), stroke and type 2 diabetes mellitus (T2DM).ResultsOver a median follow-up of 161.41 months, we recorded 14,903 CMDs events, comprising 7184 CAD cases, 1914 strokes and 7924 T2DM cases. Cox regression analysis revealed that each unit increase in the INFLA-score corresponded to a 1.5%, 1.1%, 1.2% and 2.4% increase CMDs risk (HR: 1.015, 95% CI 1.013–1.018), CAD risk (HR: 1.011, 95% CI 1.007–1.015), stroke risk (HR: 1.012, 95% CI 1.004–1.020) and T2DM risk (HR: 1.024, 95% CI 1.020–1.028), respectively. Restricted cubic spline analysis indicated a non-linear relationship between cumulative INFLA-score and CMDs risk (P = 0.044). Subgroup analysis revealed interactions between sex, age, history of lipid-lowering drug use, and INFLA-score regarding CMDs risk. Sensitivity analysis corroborated the main findings.ConclusionOur findings strongly support the close association between INFLA-score and CMDs risk, particularly notable in women, those aged < 55, and individuals with a history of lipid-lowering drug use. These findings offer new insights into the role of inflammation in obesity-related CMDs, suggesting potential applications for prevention and identification of high-risk populations.

Mediation Mendelian randomisation study on the effects of shift work on coronary heart disease and traditional risk factors via gut microbiota.

Epidemiological evidence suggests that there is an increased risk of coronary heart disease (CHD) related to jobs involving shift work (JSW), but the causality of and mechanism underlying such a relationship remain unclear. Therefore, we aimed to explore the relationship between JSW and CHD, investigating both causality and potential mediating factors. We performed univariate, multivariate, and mediation Mendelian randomisation (MR) analyses using data from large genome-wide association studies focussed on JSW and CHD, as well as data on some CHD risk factors (type 2 diabetes, hypertension, obesity, and lipids measurement) and 196 gut microbiota taxa. Single-nucleotide polymorphisms significantly associated with JSW acted as instrument variables. We used inverse-variance weighting as the primary method of analysis. Bidirectional MR analysis indicated a robust effect of JSW on increased CHD risk; however, the existence of CHD did not affect the choice of JSW. We identified a mediating effects of type 2 diabetes and hypertension in this relationship, accounting for 11.89% and 14.80% of the total effect of JSW on CHD, respectively. JSW were also causally associated with the risk of type 2 diabetes and hypertension and had an effect on nine microbial taxa. The mediating influence of the Eubacterium brachy group at the genus level explained 16.64% of the total effect of JSW on hypertension. We found limited evidence for the causal effect of JSW on obesity and lipids measurements. Our findings suggest a causal effect of JSW on CHD, diabetes, and hypertension. We also found evidence for a significant connection between JSW and alterations in the gut microbiota. Considering that certain microbial taxa mediated the effect of JSW on hypertension risk, targeting gut microbiota through therapeutics could potentially mitigate high risks of hypertension and CHD associated with JSW.

Effects of Ninjurin 2 polymorphisms on susceptibility to coronary heart disease

ABSTRACT Objective The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). Methods We conducted a case-control study with 499 CHD cases and 505 age and gender-matched controls. Five single nucleotide polymorphisms (SNPs) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390, and rs11610368) were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis to assess the association of NINJ2 polymorphisms and CHD risk-adjusted for age and gender. What’s more, risk genes and molecular functions were screened via protein-protein interaction (PPI) network and functional enrichment analysis. Results Rs118050317 in NINJ2 significantly increased CHD risk in people aged more than 60 years and women. Rs118050317 and rs7307242 had strong relationships with hypertension risk in CHD patients. Additionally, rs75750647 exceedingly raised diabetes risk in cases under multiple models, whereas rs10849390 could protect CHD patients from diabetes in allele, homozygote, and additive models. We also observed two blocks in NINJ2. Further interaction network and enrichment analysis showed that NINJ2 played a greater role in the pathogenesis and progression of CHD. Conclusion Our results suggest that NINJ2 polymorphisms are associated with CHD risk.

Correlation Between Blood Cadmium Levels and Platelet Characteristics, As Well As Their Impact on Susceptibility to Coronary Heart Disease: Findings from NHANES 2005-2018 Data.

Investigating the correlation between blood cadmium levels, platelet characteristics, and susceptibility to coronary heart disease (CHD). Utilized NHANES 2005-2018 data with covariates such as age, sex, race, marital status, and socio-economic status. Blood cadmium served as the independent variable, while platelet count (PC) and mean platelet volume (MPV) were dependent variables. The average age of the participants was 68.77 ± 11.03 years, and 67.4% of them were male. The mean values for WBC, MPV, PC, and blood cadmium were 7.53 ± 3.36 × 103 cells/µL, 11.33 ± 0.27fL, 57.61 ± 5.34 × 103 cells/µL, and 2.58 ± 0.61 µg/L, respectively. Adjusting for other variables revealed increased MPV and PC with rising blood cadmium levels in cardiac patients, indicating a higher risk of CHD in those with elevated blood cadmium. The average age of the participants was 68.77 ± 11.03 years, and 67.4% of them were male. The mean values for WBC, MPV, PC, and blood cadmium were 7.53 ± 3.36 × 103 cells/µL, 11.33 ± 0.27fL, 57.61 ± 5.34 × 103 cells/µL, and 2.58 ± 0.61 µg/L, respectively. Adjusting for other variables revealed increased MPV and PC with rising blood cadmium levels in cardiac patients, indicating a higher risk of CHD in those with elevated blood cadmium. This study enhances understanding of how cadmium impacts platelet characteristics, contributing to increased CHD risk, providing insights for primary prevention strategies.

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.

Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol

Familial hypercholesterolemia (FH) is a genetic disorder that often results in severely high low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). However, the impact of FH variants on CHD risk among individuals with moderately elevated LDL-C is not well quantified. To assess CHD risk associated with FH variants among individuals with moderately (130-189 mg/dL) and severely (≥190 mg/dL) elevated LDL-C and to quantify excess CHD deaths attributable to FH variants in US adults. A total of 21 426 individuals without preexisting CHD from 6 US cohort studies (Atherosclerosis Risk in Communities study, Coronary Artery Risk Development in Young Adults study, Cardiovascular Health Study, Framingham Heart Study Offspring cohort, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis) were included, 63 of whom had an FH variant. Data were collected from 1971 to 2018, and the median (IQR) follow-up was 18 (13-28) years. Data were analyzed from March to May 2023. LDL-C, cumulative past LDL-C, FH variant status. Cox proportional hazards models estimated associations between FH variants and incident CHD. The Cardiovascular Disease Policy Model projected excess CHD deaths associated with FH variants in US adults. Of the 21 426 individuals without preexisting CHD (mean [SD] age 52.1 [15.5] years; 12 041 [56.2%] female), an FH variant was found in 22 individuals with moderately elevated LDL-C (0.3%) and in 33 individuals with severely elevated LDL-C (2.5%). The adjusted hazard ratios for incident CHD comparing those with and without FH variants were 2.9 (95% CI, 1.4-6.0) and 2.6 (95% CI, 1.4-4.9) among individuals with moderately and severely elevated LDL-C, respectively. The association between FH variants and CHD was slightly attenuated when further adjusting for baseline LDL-C level, whereas the association was no longer statistically significant after adjusting for cumulative past LDL-C exposure. Among US adults 20 years and older with no history of CHD and LDL-C 130 mg/dL or higher, more than 417 000 carry an FH variant and were projected to experience more than 12 000 excess CHD deaths in those with moderately elevated LDL-C and 15 000 in those with severely elevated LDL-C compared with individuals without an FH variant. In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without. Further research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening.

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study

BackgroundThe residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event.MethodsData on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined.ResultsThe 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log–alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure.ConclusionThis study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Association between systolic blood pressure and low-density lipoprotein cholesterol with coronary heart disease according to age.

The impact of elevated systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD) at different stages of life is unclear. We aimed to investigate whether genetically mediated SBP/LDL-C is associated with the risk of CHD throughout life. We conducted a three-sample Mendelian randomization analysis using data from the UK Biobank including 136,648 participants for LDL-C, 135,431 participants for SBP, and 24,052 cases for CHD to assess the effect of duration of exposure to the risk factors on risk of CHD. Analyses were stratified by age at enrolment. In univariable analyses, there was a consistent association between exposure to higher LDL-C and SBP with increased odds of incident CHD in individuals aged ≤55 years, ≤60 years, and ≤65 years (p-value for heterogeneity = 1.00 for LDL-C and 0.67 for SBP, respectively). In multivariable Mendelian randomization analyses, exposure to elevated LDL-C/SBP early in life (age ≤55 years) was associated with a higher risk of CHD independent of later life levels (age >55 years) (odds ratio 1.68, 95% CI 1.20-2.34 per 1 mmol/L LDL-C, and odds ratio 1.33, 95% CI 1.18-1.51 per 10 mmHg SBP). Genetically predicted SBP and LDL-C increase the risk of CHD independent of age. Elevated SBP and LDL-C in early to middle life is associated with increased CHD risk independent of later-life SBP and LDL-C levels. These findings support the importance of lifelong risk factor control in young individuals, whose risk of CHD accumulates throughout life.

Is residential exposure to oil refineries a novel contextual risk factor for coronary heart disease?

Despite a multi-decade decrease in cardiovascular disease, geographic disparities have widened, with excess mortality concentrated within the United States (U.S.) South. Petroleum production and refining, a major contributor to climate change, is concentrated within the U.S. South and emits multiple classes of atherogenic pollutants. We investigated whether residential exposure to oil refineries could explain variation in self-reported coronary heart disease (CHD) prevalence among adults in southern states for the year 2018, where the majority of oil refinery activity occurs (Alabama, Mississippi, Louisiana, Arkansas, Texas, New Mexico, and Oklahoma). We examined census tract-level association between oil refineries and CHD prevalence. We used a double matching method to adjust for measured and unmeasured spatial confounders: one-to-n distance matching and one-to-one generalized propensity score matching. Exposure metrics were constructed based on proximity to refineries, activities of refineries, and wind speed/direction. For all census tracts within 10 km of refineries, self-reported CHD prevalence ranged from 1.2% to 17.6%. Compared to census tracts located at ≥5 km and <10 km, one standard deviation increase in the exposure within 5 km of refineries was associated with a 0.33 (95% confidence interval: 0.04, 0.63) percentage point increase in the prevalence. A total of 1119.0 (123.5, 2114.2) prevalent cases or 1.6% (0.2, 3.1) of CHD prevalence in areas within 5 km from refineries were potentially explained by exposure to oil refineries. At the census tract-level, the prevalence of CHD explained by exposure to oil refineries ranged from 0.02% (0.00, 0.05) to 47.4% (5.2, 89.5). Thus, although we cannot rule out potential confounding by other personal risk factors, CHD prevalence was found to be higher in populations living nearer to oil refineries, which may suggest that exposure to oil refineries can increase CHD risk, warranting further investigation.

CYP4V2 rs56413992 C > T was associated with the risk of coronary heart disease in the Chinese Han population: a case–control study

PurposeThe research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk.MethodsThis case–control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection.ResultsAs a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09–1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06–1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN).ConclusionThis study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.

Ultra-processed food consumption and cardiovascular events risk

Abstract Background The consumption of ultra-processed food (UPF) has been suggested to be associated with cardiovascular events risk, but their dose-response relationship have not reached a consensus. Methods We searched PubMed, EMBASE, Cochrane Library, and Web of Science databases for manuscripts published from inception to November 17, 2021, which reported the relationship between UPF consumption and cardiovascular events risk. A total of ten studies were included with 325,403 participants and 38,720 cardiovascular events cases. Using the fixed/random-effects models, hazard ratios of pooled outcomes were estimated. Results A non-linear relationship of UPF consumption with cardiovascular events risk was identified (P for heterogeneity = 0.013, P for dose-response &amp;lt; 0.001, P for non-linearity = 0.013). Compared with the lowest UPF consumption category, the third highest pooled HR for cardiovascular events risk was 1.02 (95% CI, 0.98 to 1.05), the second highest was 1.08 (95% CI, 1.04 to 1.12) and the highest was 1.24 (95% CI, 1.16 to 1.32). A linear association between UPF consumption and coronary heart disease (CHD) risk was identified (P for heterogeneity = 0.110, P for dose-response &amp;lt; 0.001, P for non-linearity = 0.202). A 10% increase in UPF consumption in daily calorie intake was associated with a 6% increase in CHD risk. UPF consumption was non-linearly associated with cerebrovascular disease (CeVD) risk (P for heterogeneity = 0.001, P for dose-response &amp;lt; 0.001, P for non-linearity = 0.026). Conclusions There was a nonlinear relationship between UPF consumption and cardiovascular events. Moderate intake of UPF was associated with a lower risk of cardiovascular events, with the lowest risk at &amp;lt;15%/day of UPF consumption out of total calorie intake. Heavy UPF consumption was significantly and positively associated with increased risk of cardiovascular events.

Abstract 13869: The Association Between DYRK4 Hypomethylation in Peripheral Blood and Coronary Heart Disease: A Case-Control Study

Backgrounds: Coronary heart disease (CHD) is a leading cause of morbidity and mortality worldwide, with myocardial infarction (MI) representing its most prevalent type. Previous studies have suggested an association between the dual-specificity tyrosine-regulated kinases ( DYRK) gene family and various cardiovascular disease risks. However, the specific role of DYRK4 in CHD, particularly in MI, remains unclear. Objective: We hereby investigated the association between blood-based DYRK4 methylation and CHD, MI and non-MI related CHD. Methods: A total of 88 CHD cases (23 MI and 65 non-MI) were diagnosed by coronary angiography and clinical presentation at Chinese People's Liberation Army General Hospital from 2018 to 2019. 93 persons who participated in the annual health examination were randomly selected as controls. The DYRK4 methylation, which contains three measurable CpG sites, was quantified by mass spectrometry of nucleic acid. Covariates-adjusted odds ratios (ORs) for -10% methylation was calculated by binary logistic regression, and receiver operating characteristic (ROC) curves were generated to evaluate the discriminatory power. Results: Decreased methylation of DYRK4_CpG_2 and DYRK4_CpG_3 in peripheral blood was significantly associated with increased CHD risk (OR: 1.49 and 1.20; p = 0.044 and 0.049). Notably, these two CpG sites were only significant in non-MI related CHD (OR: 1.71 and 1.33; p = 0.015 and 0.009) rather than MI (OR: 1.11 and 0.99; p = 0.759 and 0.968). The combination of DYRK4_CpG_2 and DYRK4_CpG_3 methylation levels could efficiently discriminate CHD, MI and non-MI related CHD patients from controls (area under curve (AUC) = 0.771, 0.795 and 0.784, respectively). Conclusion: Our study suggests that hypomethylation of DYRK4_CpG_2, DYRK4_CpG_3 in blood is associated with CHD, and DYRK4 methylation model may provide a new strategy for detection of CHD, especially non-MI related CHD.

Ratio of visceral fat area to body fat mass (VBR) is a superior predictor of coronary heart disease.

Ratio of visceral fat area to body fat mass (VBR) is a superior predictor of coronary heart disease.

Birth Weight, Cardiometabolic Factors, and Coronary Heart Disease: A Mendelian Randomization Study.

Observational studies have shown associations of birth weight (BW) with coronary heart disease (CHD), but results are inconsistent and do not distinguish the fetal or maternal effect of BW. This study aims to explore the causal association between BW and CHD, analyze the fetal and maternal contribution, and quantify mediating effects of cardiometabolic factors. Genetic variants from genome-wide association study summary-level data of own BW (N = 298 142), offspring BW (N = 210 267 mothers), and 16 cardiometabolic (anthropometric, glycemic, lipidemic, and blood pressure) factors were extracted as instrumental variables. We used two-sample Mendelian randomization study (MR) to estimate the causal effect of BW on CHD (60 801 cases and 123 504 controls from mixed ancestry) and explore the fetal and maternal contributions. Mediation analyses were conducted to analyze the potential mediating effects of 16 cardiometabolic factors using two-step MR. Inverse variance weighted analysis showed that lower BW raised the CHD risk (β -.30; 95% CI: -0.40, -0.20) and consistent results were observed in fetal-specific/maternal-specific BW. We identified 5 mediators in the causal pathway from BW to CHD, including body mass index-adjusted hip circumference, triglycerides, fasting insulin, diastolic blood pressure, and systolic blood pressure (SBP), with mediated proportion ranging from 7.44% for triglycerides to 27.75% for SBP. Causality between fetal-specific and maternal-specific BW and CHD was mediated by glycemic factors and SBP, respectively. Our findings supported that lower BW increased CHD risk and revealed that fetal-specific and maternal-specific BW may both contribute to this effect. The causality between BW and CHD was mediated by several cardiometabolic factors.

The Potential of Single Nucleotide Polymorphisms (SNPs) as Biomarkers and Their Association with the Increased Risk of Coronary Heart Disease: A Systematic Review.

Human genetic analyses and epidemiological studies showed a potential association between several types of gene polymorphism and the development of coronary heart disease (CHD). Many studies on this pertinent topic need to be investigated further to reach an evidence-based conclusion. Therefore, in this current review, we describe several types of gene polymorphisms that are potentially linked to CHD. A systematic review using the databases EBSCO, PubMed, and ScienceDirect databases was searched until October of 2022 to find relevant studies on the topic of gene polymorphisms on risk factors for CHD, especially for the factors associated with single nucleotide polymorphisms (SNPs). The risk of bias and quality assessment was evaluated by Joanna Briggs Institute (JBI) guidelines. From keyword search results, a total of 6243 articles were identified, which were subsequently narrowed to 14 articles using prespecified inclusion criteria. The results suggested that there were 33 single nucleotide polymorphisms (SNPs) that can potentially increase the risk factors and clinical symptoms of CHD. This study also indicated that gene polymorphisms had a potential role in increasing CHD risk factors that were causally associated with atherosclerosis, increased homocysteine, immune/inflammatory response, Low-Density Lipoprotein (LDL), arterial lesions, and reduction of therapeutic effectiveness. In conclusion, the findings of this study indicate that SNPs may increase risk factors for CHD and SNPs show different effects between individuals. This demonstrates that knowledge of SNPs on CHD risk factors can be used to develop biomarkers for diagnostics and therapeutic response prediction to decide successful therapy and become the basis for defining personalized medicine in future.

Traumatic brain injury and risk of heart failure and coronary heart disease: A nationwide population-based cohort study.

This study examined the long-term risks of heart failure (HF) and coronary heart disease (CHD) following traumatic brain injury (TBI), focusing on gender differences. Data from Taiwan's National Health Insurance Research Database included 29,570 TBI patients and 118,280 matched controls based on propensity scores. The TBI cohort had higher incidences of CHD and HF (9.76 vs. 9.07 per 1000 person-years; 4.40 vs. 3.88 per 1000 person-years). Adjusted analyses showed a significantly higher risk of HF in the TBI group (adjusted hazard ratio = 1.08, 95% CI = 1.01-1.17, P = 0.031). The increased CHD risk in the TBI cohort became insignificant after adjustment. Subgroup analysis by gender revealed higher HF risk in men (aHR = 1.14, 95% CI = 1.03-1.25, P = 0.010) and higher CHD risk in women under 50 (aHR = 1.32, 95% CI = 1.15-1.52, P < 0.001). TBI patients without beta-blocker therapy may be at increased risk of HF. Our results suggest that TBI increases the risk of HF and CHD in this nationwide cohort of Taiwanese citizens. Gender influences the risks differently, with men at higher HF risk and younger women at higher CHD risk. Beta-blockers have a neutral effect on HF and CHD risk.

Abstract 9935: Association of Hypertension and Growth Differentiation Factor 15 With Incident Coronary Heart Disease: The Kuakini Honolulu Heart Program

Introduction: Hypertension is a pathophysiological stress. Growth differentiation factor 15 (GDF15) is a stress-response protein, and a predictor for heart disease. The effects of the longevity genotype of FOXO3, a stress-response and prominent longevity-associated gene, on mortality vary in normotensive and hypertensive men. Hypothesis: The effect of GDF15 concentration on the risk of incident coronary heart disease (CHD) is different in men with different hypertension status. Methods: The Kuakini Honolulu Heart Program (KHHP) is a longitudinal study of cardiovascular diseases that started in 1965 involving 8,006 Japanese-American men in Hawaii. Proteomic analyses were performed using serum from KHHP exam 4 (1991-1993, ages 71-93) in a random sample (n=1,000) of men who in mid-life had been free of chronic diseases such as CHD, stroke, cancer, and diabetes. Participants were followed for incident CHD event (first event of MI, coronary insufficiency, angina, CABG, angioplasty, silent MI and CHD death) through December 1999. The Cox proportional hazards model was used to assess potential association of GDF15 concentration and hypertension (SBP/DBP≥160/95 mmHg or on anti-hypertensives) with incident CHD. Results: We excluded 5 men missing GDF15 data and 221 men with diseases including CHD, CHF, atrial fibrillation, LVH and stroke at baseline (KHHP exam 4). During 9 years of follow-up (median 7.92 years), 60 men developed CHD. To eliminate the possible recursive-effect of preclinical CHD on GDF15 at baseline, 6 CHD cases diagnosed within the first year of follow-up were excluded. So, there were 768 men available for analysis. Participants were divided, using tertiles of GDF15 concentration, into two groups: low-medium GDF15 (in low or middle tertile) and high GDF15 (in upper tertile). Multivariate Cox model adjusting for age, BMI, smoking (pack-years), cholesterol, HDL, diabetes and serum glucose showed a significant interaction effect of hypertension and high GDF15 on incident CHD (p=0.019); HR (95%CI) of high GDF15 vs low-medium GDF15 on CHD was 4.56 (1.51-13.76; p=0.007) in normotensive men, and 0.97 (0.49-1.92; p=0.93) in hypertensive men. Conclusions: High GDF15 concentration increases CHD risk in normotensive men, but not in hypertensive men.

Race-Dependent Association of High-Density Lipoprotein Cholesterol Levels With Incident Coronary Artery Disease

BackgroundPlasma lipids are risk factors for coronary heart disease (CHD) in part because of race-specific associations of lipids with CHD. ObjectivesThe purpose of this study was to understand why CHD risk equations underperform in Black adults. MethodsBetween 2003 and 2007, the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort recruited 30,239 Black and White individuals aged ≥45 years from the contiguous United States. We used Cox regression models adjusted for clinical and behavioral risk factors to estimate the race-specific hazard of plasma lipid levels with incident CHD (myocardial infarction or CHD death). ResultsAmong 23,901 CHD-free participants (57.8% White and 58.4% women, mean age 64 ± 9 years) over a median 10 years of follow-up, 664 and 951 CHD events occurred among Black and White adults, respectively. Low-density lipoprotein cholesterol and triglycerides were associated with increased risk of CHD in both races (P interaction by race >0.10). For sex-specific clinical HDL-C categories: low HDL-C was associated with increased CHD risk in White (HR: 1.22; 95% CI: 1.05-1.43) but not in Black (HR: 0.94; 95% CI: 0.78-1.14) adults (P interaction by race = 0.08); high HDL-C was not associated with decreased CHD events in either race (HR: 0.96; 95% CI: 0.79-1.16 for White participants and HR: 0.91; 95% CI: 0.74-1.12 for Black adults). ConclusionsLow-density lipoprotein cholesterol and triglycerides modestly predicted CHD risk in Black and White adults. Low HDL-C was associated with increased CHD risk in White but not Black adults, and high HDL-C was not protective in either group. Current high-density lipoprotein cholesterol–based risk calculations could lead to inaccurate risk assessment in Black adults.

Relationship of low-density lipoprotein-cholesterol and lipoprotein(a) to cardiovascular risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aimsPlasma low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are both associated with coronary heart disease (CHD). This study investigated whether elevated plasma Lp(a) concentration was associated with increased CHD risk when LDL-C was low (≤100 mg/dL) in individuals not on statin therapy. MethodsParticipants from the Multi-Ethnic Study of Atherosclerosis (MESA) (n = 4,585) were categorized into four groups: Group 1: LDL-C ≤ 100 mg/dL, Lp(a) < 50 mg/dL; Group 2: LDL-C > 100 mg/dL, Lp(a) < 50 mg/dL; Group 3: LDL-C ≤ 100 mg/dL, Lp(a) ≥ 50 mg/dL; and Group 4: LDL-C > 100 mg/dL, Lp(a) ≥ 50 mg/dL. The relationship of Lp(a) and LDL-C with time to CHD events was assessed with Kaplan Meier curves and multivariable Cox proportional hazard models. ResultsParticipants were followed for a mean of 13.4 years and a total of 315 CHD events occurred. Compared to participants with LDL-C ≤ 100 mg/dL and Lp(a) < 50 mg/dL, those with LDL-C > 100 mg/dL and Lp(a) < 50 mg/dL (Group 2) demonstrated no increased risk for CHD events (HR: 0.92; 95% CI: 0.69, 1.21). However, participants with LDL-C ≤ 100 mg/dL and Lp(a) ≥ 50 mg/dL (Group 3) and those with LDL-C > 100 mg/dL and Lp(a) ≥ 50 mg/dL (Group 4) exhibited significantly increased risk of CHD events compared to Group 1 (HR: 1.83; 95% CI: 1.02, 3.27) and Group 2 (HR: 1.61; 95% CI: 1.15, 2.26), respectively. ConclusionsWhen Lp(a) was elevated, risk of CHD events increased, regardless of baseline LDL-C.