Future Coronary Heart Disease Events Research Articles

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.

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.

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.

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).

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.

Interplay of Risk Factors and Coronary Artery Calcium for CHD Risk in Young Patients

ObjectivesThe aim of this study was to examine prevalence, predictors, and impact of coronary artery calcium (CAC) across different risk factor burdens on the prevalence of obstructive coronary artery disease (CAD) and future coronary heart disease (CHD) risk in young patients. BackgroundThe interplay of risk factors and CAC for predicting CHD in young patients aged ≤45 years is not clear. MethodsThe study included 3,691 symptomatic patients (18-45 years of age) from the WDHR (Western Denmark Heart Registry) undergoing coronary computed tomographic angiography. CHD events were myocardial infarction and late revascularization. ResultsDuring a median of 4.1 years of follow-up, 57 first-time CHD events occurred. In total, 3,180 patients (86.1%) had CAC = 0 and 511 patients (13.9%) had CAC >0. Presence of CAC increased with number of risk factors (odds ratio: 4.5 [95% CI: 2.7-7.3] in patients with >3 vs 0 risk factors). The prevalence of obstructive CAD at baseline and the rate of future CHD events increased in a stepwise manner with both higher CAC and number of risk factors. The CHD event rate was lowest at 0.5 (95% CI: 0.1-3.6) per 1,000 person-years in patients with 0 risk factors and CAC = 0. Among patients with >3 risk factors, the event rate was 3.1 (95% CI: 1.0-9.7) in patients with CAC = 0 compared with 36.3 (95% CI: 17.3-76.1) in patients with CAC >10. ConclusionsIn young patients, there is a strong interplay between CAC and risk factors for predicting the presence of obstructive CAD and for future CHD risk. In the presence of risk factors, even a low CAC score is a high-risk marker. These results demonstrate the importance of assessing risk factors and CAC simultaneously when assessing risk in young patients.

Family history of cardiovascular disease and risk of premature coronary heart disease: A matched case-control study.

Background: Self-reported family history of cardiovascular disease (CVD) is an independent risk factor for future coronary heart disease (CHD) events. However, inclusion of family history of CVD in the traditional risk scores failed to improve risk prediction of CHD. It is proposed that family history of CVD may substantially increase the risk of CHD among younger individuals. Methods: We conducted a matched case-control study with 170 hospital-based premature CHD patients (<55 years in men and <65 years in women) from a tertiary care centre in Thiruvananthapuram, Kerala and age and sex matched community-based controls in 1:1 ratio. Conditional logistic regression analysis was conducted to assess the independent association of family history of cardiovascular disease (CVD) and premature CHD. We estimated McNemar's odds ratios and their 95 percent confidence intervals. Results: The prevalence of any family history of CVD and CHD in the control population was 24% and 21%, respectively. The family history of CVD was independently associated with premature CHD (odds ratio (OR) = 9.0; 95% confidence interval (CI) 4.7-17.3). There was a dose-response relationship between family history and premature CHD as the risk increased linearly with increase in number of affected family members. Conclusions: Family history of CVD is an independent risk factor for premature CHD. The risk of premature CHD increases linearly with increase in number of affected family members. Collecting family history beyond parental history of CVD is important for risk stratification. Targeting young individuals with family history of CVD for intensive risk reduction interventions may help to prevent future events.

Family history of cardiovascular disease and risk of premature coronary heart disease: A matched case-control study

Background: Self-reported family history of cardiovascular disease (CVD) is an independent risk factor for future coronary heart disease (CHD) events. However, inclusion of family history of CVD in the traditional risk scores failed to improve risk prediction of CHD. It is proposed that family history of CVD may substantially increase the risk of CHD among younger individuals. Methods: We conducted a matched case-control study with 170 hospital-based premature CHD patients (<55 years in men and <65 years in women) from a tertiary care centre in Thiruvananthapuram, Kerala and age and sex matched community-based controls in 1:1 ratio. Conditional logistic regression analysis was conducted to assess the independent association of family history of cardiovascular disease (CVD) and premature CHD. We estimated McNemar's odds ratios and their 95 percent confidence intervals. Results: The prevalence of any family history of CVD and CHD in the control population was 24% and 21%, respectively. The family history of CVD was independently associated with premature CHD (odds ratio (OR) = 9.0; 95% confidence interval (CI) 4.7–17.3). There was a dose-response relationship between family history and premature CHD as the risk increased linearly with increase in number of affected family members. Conclusions: Family history of CVD is an independent risk factor for premature CHD. The risk of premature CHD increases linearly with increase in number of affected family members. Collecting family history beyond parental history of CVD is important for risk stratification. Targeting young individuals with family history of CVD for intensive risk reduction interventions may help to prevent future events.

Family history of cardiovascular disease and risk of premature coronary heart disease: A matched case-control study

Background: Self-reported family history of cardiovascular disease (CVD) is an independent risk factor for future coronary heart disease (CHD) events. However, inclusion of family history of CVD in the traditional risk scores failed to improve risk prediction of CHD. It is proposed that family history of CVD may substantially increase the risk of CHD among younger individuals. Methods: We conducted a matched case-control study with 170 hospital-based premature CHD patients (&lt;55 years in men and &lt;65 years in women) from a tertiary care centre in Thiruvananthapuram, Kerala and age and sex matched community-based controls in 1:1 ratio. Conditional logistic regression analysis was conducted to assess the independent association of family history of cardiovascular disease (CVD) and premature CHD. We estimated McNemar's odds ratios and their 95 percent confidence intervals. Results: The prevalence of any family history of CVD and CHD in the control population was 24% and 21%, respectively. The family history of CVD was independently associated with premature CHD (odds ratio (OR) = 9.0; 95% confidence interval (CI) 4.7–17.3). There was a dose-response relationship between family history and premature CHD as the risk increased linearly with increase in number of affected family members. Conclusions: Family history of CVD is an independent risk factor for premature CHD. The risk of premature CHD increases linearly with increase in number of affected family members. Collecting family history beyond parental history of CVD is important for risk stratification. Targeting young individuals with family history of CVD for intensive risk reduction interventions may help to prevent future events.

Standardized reporting systems for computed tomography coronary angiography and calcium scoring: A real-world validation of CAD-RADS and CAC-DRS in patients with stable chest pain

ObjectivesTo assess the prognostic implications of standardized reporting systems for coronary computed tomography angiography (CCTA) and coronary artery calcium scores (CACS) in patients with stable chest pain. BackgroundThe Coronary Artery Disease Reporting And Data System (CAD-RADS) and Coronary Artery Calcium – Data and Reporting System (CAC-DRS) aim to improve communication of CACS and CCTA results, but its influence on prognostication is unknown. MethodsImages from 1769 patients who underwent CCTA as part of the Scottish Computed Tomography of the HEART (SCOT-HEART) multi-center randomized controlled trial were assessed. CACS were classified as CAC-DRS 0 to 3 based on Agatston scores. CCTA were classified as CAD-RADS 0 to 5 based on the most clinically relevant finding per patient. The primary outcome was the five-year events of fatal and non-fatal myocardial infarction. ResultsPatients had a mean age of 58 ± 10 years and 56% were male. CAC-DRS 0, 1, 2 and 3 occurred in 642 (36%), 510 (29%), 239 (14%) and 379 (21%) patients respectively. CAD-RADS 0, 1, 2, 3, 4A, 4B and 5 occurred in 622 (35%), 327 (18%), 211 (12%), 165 (9%), 221 (12%), 42 (2%) and 181 (10%) patients respectively. Patients classified as CAC-DRS 3 were at an increased risk of fatal or non-fatal myocardial infarction compared to CAC-DRS 0 patients (hazard ratio (HR) 9.41; 95% confidence interval (CI) 3.24, 27.31; p < 0.001). Patients with higher CAD-RADS categories were at an increased risk of fatal or non-fatal myocardial infarction, with patients classified as CAD-RADS 4B at the highest risk compared to CAD-RADS 0 patients (HR 19.14; 95% CI 4.28, 85.53; p < 0.001). ConclusionPatients with higher CAC-DRS and CAD-RADS scores were at increased risk of subsequent fatal and non-fatal myocardial infarction. This confirms that the classification provides additional prognostic discrimination for future coronary heart disease events.

Metabolic syndrome severity is significantly associated with future coronary heart disease in Type 2 diabetes

BackgroundThe severity of the metabolic syndrome (MetS) is significantly associated with future coronary heart disease (CHD) among individuals without baseline Type 2 diabetes. However, the validity of assessing MetS severity among individuals with diabetes is unknown.ObjectiveTo assess for differences in MetS severity by timing of Type 2 diabetes diagnosis and to assess for associations between MetS severity and future CHD among individuals with diabetes.MethodsWe analyzed data from participants of the Atherosclerosis Risk in Communities study, including 1419 with- and 7241 without diabetes, followed during 4 visits and adjudicated CHD diagnoses over a 20-year period. We used Cox-regression techniques to assess hazard ratios (HR) of CHD based on a sex- and race/ethnicity-specific MetS-severity Z-score (standard MetS score) and a similar MetS-severity score formulated without incorporating glucose as a component of MetS (no-glucose MetS score).ResultsFor both the standard- and no-glucose MetS-severity scores, scores were highest in the baseline-diabetes group, lowest in the never-diabetes group and intermediate in the incident-diabetes groups. Among participants with diabetes, increasing MetS-severity score at baseline was associated with incident CHD, using both the standard MetS score (HR 1.29, 95% confidence interval [CI] 1.21, 1.39) and the no-glucose score (HR 1.42, CI 1.24, 1.62) (both p < 0.001). For the baseline-diabetes group, this relationship remained significant when Visit 2 Hemoglobin-A1c was included in the model, both for the standard MetS score (HR 1.21, CI 1.09, 1.34; p < 0.001) and the no-glucose score (HR 1.25, CI 1.04, 1.51; p = 0.02).ConclusionsMetS severity appears to provide an estimate of metabolic disarray in the setting of diabetes and is predictive of future CHD events beyond HbA1c. Identifying MetS severity among individuals with diabetes may help in identifying those at higher risk, who could then receive further preventative treatment.

Systematic Review of Validity Assessments of Framingham Risk Score Results in Health Economic Modelling of Lipid-Modifying Therapies in Europe.

BackgroundThe Framingham Risk Score is used both in the clinical setting and in health economic analyses to predict the risk for future coronary heart disease events. Based on an American population, the Framingham Risk Score has been criticised for potential overestimation of risk in European populations.ObjectiveWe investigated whether the use of the Framingham Risk Score actually was validated in health economic studies that modelled the effects of lipid-lowering treatment with statins on coronary heart disease events in European populations.MethodsIn this systematic literature review of all relevant published studies in English (literature searched September 2016 in PubMed, EMBASE and SCOPUS), 99 studies were identified and 22 were screened in full text, 18 of which were included. Key data were extracted and synthesised narratively.ResultsThe only type of validation identified was a comparison against coronary heart disease risk data from one primary preventive and one secondary preventive clinical investigation, and from observational population data in one study. Taken together, those three studies reported an overall satisfactory accuracy in the results obtained by Framingham Risk Score predictions, but the Framingham Risk Score tended to underestimate non-fatal myocardial infarctions. In five studies, potential issues in applying the Framingham Risk Score on a European population were not addressed.ConclusionFurther studies are needed to ascertain that the Framingham Risk Score can accurately predict cardiovascular outcome in health economic modelling studies on lipid-lowering therapy in European populations. Future modelling studies using the Framingham Risk Score would benefit from validating the results against other data.Electronic supplementary materialThe online version of this article (doi:10.1007/s40273-017-0578-1) contains supplementary material, which is available to authorized users.

Comparison of QRS Duration and Associated Cardiovascular Events in American Indian Men Versus Women (The Strong Heart Study)

Electrocardiographic QRS duration at rest is associated with sudden cardiac death and death from coronary heart disease in the general population. However, its relation to cardiovascular events in American Indians, a population with persistently high cardiovascular disease mortality, is unknown. The relation of QRS duration to incident cardiovascular disease during 17.2years of follow-up was assessed in 1,851 male and female Strong Heart Study participants aged 45 to 74years without known cardiovascular disease at baseline. Cox regression with robust standard error estimates was used to determine the association between quintiles of QRS duration and incident cardiovascular disease in gender-stratified analyses, adjusted for age, systolic blood pressure, hypertension, antihypertensive medication use, body mass index, current smoking, diabetes, total cholesterol, high-density lipoprotein cholesterol, and albuminuria. In women only, QRS duration in the highest quintile (≥105ms) conferred significantly higher risk of cardiovascular disease than QRS duration in the lowest quintile (64 to 84ms) (hazard ratio 1.6, 95% CI 1.1 to 2.4) likely because of higher risks of coronary heart disease (hazard ratio 1.8, 95% CI 1.1 to 3.1) and myocardial infarction (hazard ratio 2.1, 95% CI 1.0 to 4.7). Furthermore, when added to the Strong Heart Study Coronary Heart Disease Risk Calculator, QRS duration significantly improved prediction of future coronary heart disease events in women (Net Reclassification Index 0.17, 95% CI 0.06 to 0.47). In conclusion, QRS duration is an independent predictor of cardiovascular disease in women in the Strong Heart Study cohort and may have value in estimating risk in populations with similar risk profiles and a high lifetime incidence of cardiovascular disease.

Comparing Arterial Function Parameters for the Prediction of Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA).

Arterial dysfunction has been linked to decline in cardiac function and increased risk of cardiovascular disease events. We calculated the value of arterial function, measured at baseline (2000-2002), in predicting time to first coronary heart disease (CHD) event (median follow-up, 10.2 years) among participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Measures included the following: C1 and C2, derived from diastolic pulse contour analysis from the radial artery blood pressure waveform obtained by tonometry (n=6,336); carotid distensibility and Young's elastic modulus at the carotid artery, derived from carotid artery ultrasonography (n=6,531 and 6,528); and aortic distensibility, measured using cardiac magnetic resonance imaging (n=3,677). After adjustment, the hazard ratio for a CHD event per standard-deviation increment in arterial function was 0.97 (95% confidence interval (CI): 0.86, 1.10) for C1, 0.73 (95% CI: 0.63, 0.86) for C2, 0.98 (95% CI: 0.86, 1.11) for carotid distensibility, 0.99 (95% CI: 0.90, 1.09) for Young's modulus, and 0.90 (95% CI: 0.74, 1.10) for aortic distensibility. We examined the area under the receiver operating characteristic curve for the model with full adjustment plus the addition of each measure individually. C2 provided additional discrimination for the prediction of CHD (area under the curve=0.736 vs. 0.743; P=0.04). Lower C2 was associated with a higher risk of future CHD events.

The relationship between insulin like growth factor-1 and coronary artery calcium score in cardiovascular asymptomatic adult men

Objectives: The relationship between insulin-like growth factor-1 (IGF-1) and cardiovascular risk factors remains controversial. Our aim was to determine whether the serum levels of IGF-1 associate with coronary artery calcium score (CACS), a predictive marker for future coronary heart disease (CHD) events, in cardiovascular asymptomatic adult men.

Nonlinear relation between pulse pressure and coronary heart disease in patients with type 2 diabetes or hypertension.

Wide pulse pressure (PP) is an independent predictor of coronary heart disease (CHD). However, the linearity of the relation between PP and CHD was not examined before. We aimed to examine this relation in patients with type 2 diabetes and/or hypertension. A total of 3120 patients (including 2607 with diabetes and 1586 with hypertension) were followed for 7.8 years. Physician-adjudicated first hard CHD event was the primary outcome. Cox regression analysis was used to investigate the association between PP and incident CHD. Restricted cubic splines were used to investigate nonlinear relations. Four spline covariates were defined between 30, 40, 50, 60, and 70 mmHg. The null-hypothesis of the linearity of the relation between PP and CHD was rejected (P value = 0.004). The second, third, and fourth spline covariates were significant (P value = 0.02, P value = 0.02 and P value = 0.01, respectively), supporting a nonlinear relation in corresponding PP intervals. Patients with PP less than 45 mmHg and PP more than 55 mmHg had increased risk of future CHD event, compared with those with PP between 45 and 55 mmHg [hazard ratio (HR) = 1.33 (1.00-1.77) and HR = 1.67 (1.23-2.27), respectively]. This remained significant after controlling for systolic, diastolic, or mean arterial pressures in wide PP group. However, adjustment for traditional cardiovascular risk factors (especially age) attenuated the relation in those with wide PP. The relation between PP and CHD is nonlinear in patients with type 2 diabetes and hypertension. Both narrow and wide PPs increase risk of future hard CHD events. The association between wide PP and CHD is independent from SBP, DBP, or mean arterial pressure.

Diabetes Isn't Equivalent to Past Coronary Heart Disease as a Risk Factor for Future CHD Events

For many years, patients with diabetes and no known coronary heart disease (CHD) were thought to have the same risk for future myocardial infarction

Capsule Commentary on Rana et al., Diabetes and Prior Coronary Heart Disease Are Not Necessarily Risk Equivalent for Future Coronary Heart Disease Events.

T he prevalence of diabetes mellitus (DM) has risen dramatically over the past decades as obesity rates have increased in the United States. Recent estimates suggest that approximately 9 % of the U.S. population, or over 29 million Americans, have DM, with the great majority having Type 2 DM. While cardiovascular disease is known to be the leading cause of death among those with diabetes, there has been controversy as to whether prevalent diabetes portends the same risk for future cardiovascular events as prevalent coronary heart disease (CHD). Delineating diabetes as a CHD equivalent or a CHD risk factor is critical to improving the accuracy of cardiovascular risk prediction and in developing tailored risk reduction strategies. Rana and colleagues analyzed electronic health record data from the Kaiser Permanente Northern California health care system, which includes over 1.5 million members. This study demonstrated that the risk of a CHD event over a 10-year follow-up period was significantly lower for those with diabetes alone as compared to those with prior CHD; these findings appear to refute previous data showing that prevalent diabetes is a CHD equivalent. Most interestingly, those with diabetes for the longest duration, or for ten or more years in the cohort, had a similar risk of CHD events as those with CHD alone. The findings are robust, given that much of the prior data examining diabetes as a CHD risk equivalent comes from metaanalyses with inherent methodologic limitations, and this study was done in a large, ethnically and racially diverse population from a real-world setting. Additionally, sex-stratified analyses of CHD event rates in this population help to identify whether CHD risk based on prevalent diabetes differs betweenmen andwomen. One area for future work with this study cohort would be to evaluate differences in CHD event rates across racial and ethnic groups among those with diabetes and/or CHD as compared to those without either disease. Overall, these findings support the use of outcomes data from diverse patient populations for creating and refining cardiovascular risk prediction models, as was used in the creation of the 2013 ACC/AHA cardiovascular risk estimator. The author has no conflict with any of the material in this manuscript. Funding support for the author is provided by the Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH). The views expressed in this manuscript are those of the author and do not necessarily represent the views of the National Heart, Lung, andBlood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.