Hyperhomocysteinemia as an Independent Risk Factor for Coronary Heart Disease. Comparison with Conventional Risk Factors

The present study was designed to evaluate the strength of association of raised plasma homocysteine concentration as a risk factor for coronary heart disease independent of conventional risk factor. It was a case control study conducted at Punjab Institute of Cardiology Lahore. A total of 210 subjects aged 25 to 60 years comprising of 105 newly admitted patients of CHD as cases and 105 age and sex matched healthy individuals with no history of CHD as control were recruited for the study. Fasting blood samples were obtained from cases and controls. Plasma homocysteine was analyzed by fluorescence polarization immunoassay (FPIA) method on automated immunoassay analyzer (Abbott IMX). Total cholesterol, triglyceride and HDL cholesterol were analyzed using calorimetric kit methods. The concentration of LDL cholesterol was calculated using Friedewald formula. The patients were also assessed for traditional risk factors such as age, sex, family history of CVD, hypertension, smoking and physical activity, and were compared with control subjects. The collected data was entered in SPSS version 24 for analysis and interpretation.The mean age in controls and experimental groups were 43.00± 8.42 years and 44.72± 8.59 years with statistically same distribution (p- value= 0.144). The mean plasma homocysteine for cases was 22.33± 9.22 µmol/L where as it was 12.59±3.73 µmol/L in control group. Highly significant difference was seen between the mean plasma level of homocysteine in cases and controls (p˂0.001).Simple logistic regression indicates a strong association of coronary heart disease with hyperhomocysteinemia (OR 7.45), which remained significantly associated with coronary heart disease by multivariate logistic regression (OR 7.10, 95%C1 3.12-12.83, p=0.000). The present study concludes that elevated levels of Plasma homocysteine is an independent risk factor for coronary heart disease independent of conventional risk factors and can be used as an indicator for predicting the future possibility for the onset of CVD.

Disaggregating proportional multistate lifetables by population heterogeneity to estimate intervention impacts on inequalities

Background Simulation models can be used to quantify the projected health impact of interventions. Quantifying heterogeneity in these impacts, for example by socioeconomic status, is important to understand impacts on health inequalities. We aim to disaggregate one type of Markov macro-simulation model, the proportional multistate lifetable, ensuring that under business-as-usual (BAU) the sum of deaths across disaggregated strata in each time step returns the same as the initial non-disaggregated model. We then demonstrate the application by deprivation quintiles for New Zealand (NZ), for: hypothetical interventions (50% lower all-cause mortality, 50% lower coronary heart disease mortality) and a dietary intervention to substitute 59% of sodium with potassium chloride in the food supply. Methods We developed a disaggregation algorithm that iteratively rescales mortality, incidence and case-fatality rates by time-step of the model to ensure correct total population counts were retained at each step. To demonstrate the algorithm on deprivation quintiles in NZ, we used the following inputs: overall (non-disaggregated) all-cause mortality & morbidity rates, coronary heart disease incidence & case fatality rates; stroke incidence & case fatality rates. We also obtained rate ratios by deprivation for these same measures. Given all-cause and cause-specific mortality rates by deprivation quintile, we derived values for the incidence, case fatality and mortality rates for each quintile, ensuring rate ratios across quintiles and the total population mortality and morbidity rates were returned when averaged across groups. The three interventions were then run on top of these scaled BAU scenarios. Results The algorithm exactly disaggregated populations by strata in BAU. The intervention scenario life years and health adjusted life years (HALYs) gained differed slightly when summed over the deprivation quintile compared to the aggregated model, due to the stratified model (appropriately) allowing for differential background mortality rates by strata. Modest differences in health gains (HALYs) resulted from rescaling of sub-population mortality and incidence rates to ensure consistency with the aggregate population. Conclusion Policy makers ideally need to know the effect of population interventions estimated both overall, and by socioeconomic and other strata. We demonstrate a method and provide code to do this routinely within proportional multistate lifetable simulation models and similar Markov models.

AK098656: a new biomarker of coronary stenosis severity in hypertensive and coronary heart disease patients

Background AK098656 may be an adverse factor for coronary heart disease (CHD), especially in patients with hypertension. This study aimed to analyze the effect of AK098656 on CHD and CHD with various complications. Methods A total of 117 CHD patients and 27 healthy control subjects were enrolled in the study. Plasma AK098656 expression was determined using the quantitative real-time polymerase chain reaction. Student’s t-test was used to compare AK098656 expression levels in different groups. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to quantify the discrimination ability between CHD patients and health controls and between CHD and CHD + complications patients. The relationship between AK098656 and coronary stenosis was analyzed using Spearman’s correlation. Results AK098656 expression was remarkably higher in CHD patients than in healthy controls (P = 0.03). The ROC curve revealed an effective predictive AK098656 expression value for CHD risk, with an AUC of 0.656 (95% CI 0.501–0.809). Moreover, AK098656 expression was increased in CHD + complications patients compared to CHD patients alone (P = 0.005), especially in patients with hypertension (CHD + hHTN, P = 0.030). The ROC curve revealed a predictive AK098656 prognostic value for discriminating between CHD and CHD + hHTN patients, with an AUC of 0.666 (95% CI 0.528–0.805). There was no significant difference in AK098656 expression in CHD patients with diabetes mellitus compared to CHD patients alone. In addition, AK098656 expression in CHD patients was positively correlated with stenosis severity (R = 0.261, P = 0.006). Conclusion AK098656 expression was significantly increased in patients with CHD, especially those with hypertension, and its expression level was positively correlated with the degree of coronary stenosis. This implied that AK098656 may be a risk factor for CHD and can potentially be applied in clinical diagnosis or provide a novel target for treatment.

Coronary Heart Disease and Cardiovascular Risk Factors in Patients With Idiopathic Inflammatory Myopathies: A Systemic Review and Meta-Analysis

Objectives:It is well-established that the association between atherosclerotic cardiovascular diseases (ASCVD) and connective tissue diseases (CTDs), but the relationship between coronary heart disease (CHD) and idiopathic inflammatory myopathies (IIMs) remains controversial yet. The aim of this meta-analysis is to systematically evaluate the risk of CHD in IIMs patients. In addition, we explore differences in traditional cardiovascular risk factors between IIMs patients and controls.Methods:We searched Pubmed, EMBASE and Cochrane databases to identify relevant observational studies published in English up to August 2021. Pooled relative risk (RR) and 95% confidence interval (CI) was calculated using the generic inverse variance method for the risk of CHD. A meta-proportion analysis was conducted to assess differences in cardiovascular risk factors between two groups.Results:A total of 15 studies met inclusion criteria: seven studies focused on CHD and nine studies focused on traditional cardiovascular risk factors. The results demonstrated that IIMs patients had a higher risk of CHD (RR = 2.19, 95% CI: 1.40–3.42). Hypertension (OR = 1.44, 95% CI: 1.28–1.61), diabetes mellitus (OR = 1.67, 95% CI: 1.55–1.81) and dyslipidemia (OR = 1.48, 95% CI: 1.19–1.84) were more prevalent in IIMs patients compared with controls. However, there was a significant heterogeneity among studies assessing the risk of CHD and hypertension. Subgroup analysis demonstrated that definition of CHD, country and sample size may be potential sources of heterogeneity.Conclusions:IIMs patients were at increased risk of CHD, and traditional cardiovascular risk factors appeared more prevalent in IIMs patients. This systemic review offers the proof that early appropriate interventions could reduce cardiovascular-associated morbidity and mortality in IIMs patients.

Functional Deletion/Insertion Promoter Variants in SCARB1 Associated With Increased Susceptibility to Lipid Profile Abnormalities and Coronary Heart Disease

Background: Genetic variants in Scavenger receptor Class B Type 1 (SCARB1) influencing high-density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) risk were identified by recent genome-wide association studies. Further study of potential functional variants in SCARB1 may provide new ideas of the complicated relationship between HDL-C and CHD.Methods: 2000 bp in SCARB1 promoter region was re-sequenced in 168 participants with extremely high plasma HDL-C and 400 control subjects. Putative risk alleles were identified using bioinformatics analysis and reporter-gene assays. Two indel variants, rs144334493 and rs557348251, respectively, were genotyped in 5,002 CHD patients and 5,175 control subjects. The underlying mechanisms were investigated.Results: Through resequencing, 27 genetic variants were identified. Results of genotyping in 5,002 CHD patients and 5,175 control subjects revealed that rs144334493 and rs557348251 were significantly associated with increased risk of CHD [odds ratio (OR): 1.28, 95% confidence interval (CI): 1.09 to 1.52, p = 0.003; OR: 2.65, 95% CI: 1.66–4.24, p = 4.4 × 10−5). Subsequent mechanism experiments demonstrated that rs144334493 deletion allele attenuated forkhead box A1 (FOXA1) binding to the promoter region of SCARB1, while FOXA1 overexpression reversely increased SR-BI expression.Conclusion: Genetic variants in SCARB1 promoter region significantly associated with the plasma lipid levels by affecting SR-BI expression and contribute to the susceptibility of CHD.

Intelligent Algorithm-Based Multislice Spiral Computed Tomography to Diagnose Coronary Heart Disease

In this study, dictionary learning and expectation maximization reconstruction (DLEM) was combined to denoise 64-slice spiral CT images, and results of coronary angiography (CAG) were used as standard to evaluate its clinical value in diagnosing coronary artery diseases. 120 patients with coronary heart disease (CHD) confirmed by CAG examination were retrospectively selected as the research subjects. According to the random number table method, the patients were divided into two groups: the control group was diagnosed by conventional 64-slice spiral CT images, and the observation group was diagnosed by 64-slice spiral CT images based on the DLEM algorithm, with 60 cases in both groups. With CAG examination results as the standard, the diagnostic effects of the two CT examination methods were compared. The results showed that when the number of iterations of maximum likelihood expectation maximization (MLEM) algorithm reached 50, the root mean square error (RMSE) and peak signal to noise ratio (PSNR) values were similar to the results obtained by the DLEM algorithm under a number of iterations of 10 when the RMSE and PSNR values were 18.9121 dB and 74.9911 dB, respectively. In the observation group, 28.33% (17/60) images were of grade 4 or above before processing; after processing, it was 70% (42/60), significantly higher than the proportion of high image quality before processing. The overall diagnostic consistency, sensitivity, specificity, and accuracy (88.33%, 86.67%, 80%, and 85%) of the observation group were better than those in the control group (60.46%, 62.5%, 58.33%, and 61.66%). In conclusion, the DLEM algorithm has good denoising effect on 64-slice spiral CT images, which significantly improves the accuracy in the diagnosis of coronary artery stenosis and has good clinical diagnostic value and is worth promoting.

Does weight mediate the effect of smoking on coronary heart disease? Parametric mediational g-formula analysis

Background In settings in which there are time-varying confounders affected by previous exposure and a time-varying mediator, natural direct and indirect effects cannot generally be estimated unbiasedly. In the present study, we estimate interventional direct effect and interventional indirect effect of cigarette smoking as a time-varying exposure on coronary heart disease while considering body weight as a time-varying mediator. Methods To address this problem, the parametric mediational g-formula was proposed to estimate interventional direct effect and interventional indirect effect. We used data from the Multi-Ethnic Study of Atherosclerosis to estimate effect of cigarette smoking on coronary heart disease, considering body weight as time-varying mediator. Results Over a 11-years period, smoking 20 cigarettes per day compared to no smoking directly (not through weight) increased risk of coronary heart disease by an absolute difference of 1.91% (95% CI: 0.49%, 4.14%), and indirectly decreased coronary heart disease risk by -0.02% (95% CI: -0.05%, 0.04%) via change in weight. The total effect was estimated as an absolute 1.89% increase (95% CI: 0.49%, 4.13%). Conclusion The overall absolute impact of smoking to incident coronary heart disease is modest, and we did not discern any important contribution to this effect relayed through changes to bodyweight. In fact, changes in weight because of smoking have no meaningful mediating effect on CHD risk.