Ischemic Heart Disease Events Research Articles

Alcohol – The myth of cardiovascular protection

To investigate potential biases that exist in available epidemiological evidence resulting in negative associations or underestimation of cardiovascular (CV) risk associated with alcohol consumption. UK Biobank involved baseline data collection from 22 assessment centres across the United Kingdom. The cohort consisted of 333259 alcohol consumers and 21710 never drinkers. Participants were followed up for a median 6.9 years capturing incident fatal and non-fatal CV events, ischemic heart disease and cerebrovascular disease. Alcohol intake was reported as grams/week. Using never drinkers as reference, alcohol from all drink types combined (hazard ratios ranging between 0.61 and 0.74), beer/cider (0.70-0.80) and spirits combined, and all wines combined (0.66-0.77) associated with a reduced risk for all outcome measures (all CV events, ischaemic heart disease, cerebrovascular disease). In continuous analysis, alcohol captured from all drink types combined (hazard ratio, 1.08, 95% confidence interval, 1.01-1.14), and beer/cider and spirits combined (1.24, 1.17-1.31) associated with an increased risk for overall CV events, however hazard ratios were stronger for beer/cider and spirits (P<0.0001). Wine associated with a reduced risk for overall CV events (0.92, 0.86-0.98) and ischemic heart disease (0.75, 0.67-0.84). This negative relationship with overall CV events was lost after excluding ischemic heart disease events (1.00, 0.93-1.08), while the positive association of alcohol captured from beer/cider and spirits remained significant (1.30, 1.22-1.40). This positive association with overall CV events was present even when consuming less than 14 units per week. Avoiding potential biases prevents underestimation of cardiovascular risk and indicates that consuming up to 14 units per week also associated with increased CV risk in the general population.

Lipoprotein(a) and SARS-CoV-2 infections: Susceptibility to infections, ischemic heart disease and thromboembolic events.

BackgroundComorbidities including ischemic heart disease (IHD) worsen outcomes after SARS‐CoV‐2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS‐CoV‐2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow‐up of the pandemic.MethodCohort study using data from the UK Biobank during the SARS‐CoV‐2 pandemic. Baseline Lp(a) was compared between SARS‐CoV‐2 positive patients and the population controls.ResultsSARS‐CoV‐2 positive patients had Lp(a) concentrations similar to the population controls. The risk for IHD increased with higher Lp(a) concentrations in both, the population controls (n = 435,104) and SARS‐CoV‐2 positive patients (n = 6937). The causality of the findings was supported by a genetic risk score for Lp(a). A SARS‐CoV‐2 infection modified the association with a steeper increase in risk for infected patients (interaction p‐value = 0.03). Although SARS‐CoV‐2 positive patients had a five‐times higher frequency of thromboembolic events compared to the population controls (1.53% vs. 0.31%), the risk was not influenced by Lp(a).ConclusionsSARS‐CoV‐2 infections enforce the association between high Lp(a) and IHD but the risk for thromboembolic events is not influenced by Lp(a).

Risk for ischemic stroke and coronary heart disease associated with migraine and migraine medication among older adults

BackgroundMigraine has been associated with cardiovascular disease (CVD) events among middle-aged adults. The objective of this study was to determine the risk for ischemic stroke and coronary heart disease (CHD) events among older adults with versus without migraine.MethodsThis retrospective cohort study was conducted using data from US adults ≥66 years of age with Medicare health insurance between 2008 and 2017. After stratification by history of CVD, patients with a history of migraine were matched 1:4 to those without a history of migraine, based on calendar year, age, and sex. Patients were followed through December 31, 2017 for ischemic stroke and CHD events including myocardial infarction or coronary revascularization. All analyses were done separately for patients with and without a history of CVD.ResultsAmong patients without a history of CVD (n = 109,950 including n = 21,990 with migraine and n = 87,960 without migraine), 1789 had an ischemic stroke and 3552 had a CHD event. The adjusted hazard ratio (HR) among patients with versus without migraine was 1.20 (95% confidence interval [95%CI], 1.07–1.35) for ischemic stroke and 1.02 (95%CI, 0.93–1.11) for CHD events. Compared to patients without migraine, those with migraine who were taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.43 [95%CI, 1.20–1.69]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.79 [95%CI, 0.67–0.93]). Among patients with a history of CVD (n = 79,515 including n = 15,903 with migraine and n = 63,612 without migraine), 2960 had an ischemic stroke and 7981 had a CHD event. The adjusted HRs (95%CI) for ischemic stroke and CHD events associated with migraine were 1.27 (1.17–1.39) and 0.99 (0.93–1.05), respectively. Patients with migraine taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.21 [95%CI, 1.07–1.36]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.83 [95%CI, 0.72–0.95]), each versus those without migraine.ConclusionsOlder adults with migraine are at increased risk for ischemic stroke. The risk for ischemic stroke among older adults with migraine may differ by migraine medication classes.

Cardiac reparative therapy with adipose graft transposition procedure (AGTP) improves electrophysiological remodeling of chronic myocardial infarction

Abstract Background Cardiac regeneration is a promising therapeutic option for patients with prior myocardial infarction (MI). Adipose graft transposition procedure (AGTP) is a cardiac reparative therapy consisting of the transposition of a vascularized adipose flap from the autologous pericardium over the epicardial scar area, which has shown to reduce the infarct size and improve the left ventricular function. Purpose To assess the impact of the AGTP on the electrophysiological remodeling of the post-MI scar by means of electrophysiological study (EPS), high density (HD) mapping, and 3D contrast-enhanced MRI (ceMRI). Methods A lateral MI was induced in 14 Landrace X Large White pigs by coil deployment at the first marginal branch of the circumflex artery. A 3D ceMRI, EPS and endocardial HD mapping were performed 2 (baseline) and 6 weeks post-MI (30 day post-treatment). Subjects were randomized to AGTP (n=8) or sham surgery (n=6) following baseline tests. Voltage and activation maps were blindly analyzed off-line with self-customized ParaView-based software. ceMRI was post-processed with ADAS3D. Conventional bipolar and unipolar voltage cut-offs were used (0.5–1.5mV and 6.7mV, respectively). Conduction velocity (CV) was determined for every pair of contiguous points. Areas of CV were quantified for every 0.2m/s steps (&amp;lt;0.2 - 4 m/s). Results At follow-up, and compared to the sham group, the AGTP group showed a significant reduction of the border zone area in both bipolar voltage mapping (−18±50% vs +10±144%, p=0.043) and ceMRI (−2.0±1.7 vs +1.1±2.8g; p=0.047), as well as a reduction in dense scar mass by ceMRI (−1.1±0.7g vs. +0.6±0.9 g, p=0.001). The AGTP group had a significant reduction of the size of very-slow CV areas (&amp;lt;0.2 m/s), compared to the sham group (−3.5±3.4 vs. +1.5±3.8 mm2, p=0.022), without differences in other CV ranges. EPS did not induce ventricular tachycardia in any subject at baseline, and only in 1 of the sham group at the follow-up. Conclusions Cardiac reparative therapy with AGTP of post-MI scar reduced the size of border zone tissue and very-slow conduction zones and could provide a protective effect against arrhythmic events in ischemic heart disease. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FIS grant - Instituto de Salud Carlos III

Dairy intake and risk of major cardiovascular events: a prospective cohort study of 0.5 million Chinese adults

Abstract Background Evidence on the association between dairy consumption and risk of cardiovascular disease has been highly inconsistent, with findings suggesting either harmful, neutral or beneficial effects. In addition, a very large majority of the previous studies on this topic were conducted among populations in Europe and North America who usually consume a higher amount of dairy products and very few data, particularly prospective data, come from China where the dairy consumption level is low. Purpose We therefore investigated the associations between intake of dairy products and incidence of several major types of cardiovascular diseases in Chinese adults. Methods During 2004–2008, the prospective China Kadoorie Biobank Study recruited slightly over 0.5 million adults from ten diverse regions (five urban and five rural) across China. Information on the consumption frequency of dairy products was collected at baseline and periodic resurveys, using a validated interviewer-administered laptop-based questionnaire. Over a mean follow-up of 10.9 years, there were 47,128 incident ischaemic heart disease events, 43,481 ischaemic strokes and 9749 intracerebral haemorrhages among 489,595 study participants, who did not report a prior history of cardiovascular disease at baseline. Cox regression analyses were performed to estimate multivariable-adjusted hazard ratios (HRs) for incident events associated with dairy intake. Results Overall, 69.3% of participants reported never or rare consumption (i.e. non-consumers) and 11.3% of them reported regular consumption (i.e. ≥4 days/week) of dairy products, with milk accounting for the largest proportion of total dairy intake (∼77%). Male and female regular dairy consumers had 2.1/1.5 and 1.7/1.1 mmHg lower systolic/diastolic blood pressure, respectively compared to non-consumers. In a subset (∼18,000) of participants with blood lipid levels measured, regular dairy consumers had ∼0.1 mmol/L higher LDL levels than non-consumers. After adjusting for a range of potential confounders, including sociodemographic and lifestyle factors, BMI and other dietary factors, dairy consumption was positively and significantly associated with risk of ischaemic heart disease, with the adjusted HR per 50 g/day increase in usual dairy consumption being 1.11 (95% confidence interval [CI] 1.09–1.14). Dairy consumption was not significantly associated with risk of ischemic stroke but was inversely associated with risk of intracerebral haemorrhage, with each 50 g/day increase in usual dairy consumption being associated with 17% lower risk (HR 0.83, 0.78–0.88). These associations remained significant after additional adjustment for systolic blood pressure. Conclusion In this large study of Chinese adults, higher intake of dairy products was associated with a higher risk of ischaemic heart disease but a lower risk of intracerebral haemorrhage. The exact mechanisms underlying such associations require further investigation. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The CKB baseline survey and the first re-survey were supported by the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up has been supported by Wellcome grants to Oxford University (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z) and grants from the National Key Research and Development Program of China (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) and from the National Natural Science Foundation of China (91843302). The UK Medical Research Council (MC_UU_00017/1,MC_UU_12026/2 MC_U137686851), Cancer Research UK (C16077/A29186; C500/A16896) and the British Heart Foundation (CH/1996001/9454), provide core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit at Oxford University for the project.

Associations of red meat, poultry, fish and egg intake with risk of cardiovascular disease: an 11-year prospective study of the China Kadoorie Biobank

Abstract Background Higher red meat intake and lower fish intake have been associated with increased risk of cardiovascular disease (CVD), while the relevance of poultry and egg intake for CVD incidence remains inconclusive. Furthermore, most of the prospective evidence comes from studies in the Western populations, with limited data from China where the CVD patterns are largely different. Purpose We therefore investigated the associations of red meat, poultry, fish and egg intake with risks of several major types of CVD in Chinese adults. Methods The China Kadoorie Biobank is a prospective study which recruited ∼512,000 adult participants from ten diverse localities during 2004–08. At baseline and periodic resurveys, information on the consumption frequency of major food groups was collected using a validated interviewer-administered laptop-based questionnaire, together with medical history, socio-demographic and other lifestyle factors. During an average follow-up of 10.9 years, 47,128 incident ischaemic heart disease events, 43,481 ischaemic strokes and 9749 intracerebral haemorrhages were recorded among 489,595 participants, who did not have a prior history of CVD at baseline. Cox regression was used to calculate adjusted hazard ratios (HRs) relating dietary exposures to CVD risk. Results There were 47.2%, 1.4%, 9.0% and 24.1% of participants at baseline who regularly consumed (i.e. ≥4 days/week) red meat, poultry, fish and eggs, respectively. After adjusting for potential confounders, including body mass index and other dietary factors under study, egg consumption was significantly associated with lower risks of ischaemic heart disease and ischaemic stroke, with each 50 g/day increase in estimated habitual egg consumption being associated with 18% (HR 0.82, 95% confidence interval [CI] 0.75–0.90) and 24% lower risks (HR 0.76, 95% CI 0.69–0.84), respectively. Inverse associations were also observed between intakes of red meat, fish and eggs and risk of intracerebral haemorrhage, with adjusted HRs for 50 g/day higher intake being 0.84 (95% CI 0.74–0.97), 0.86 (95% CI 0.74–0.99) and 0.42 (95% CI 0.34–0.51), respectively. Conclusion This large prospective study of Chinese adults showed that higher intake of eggs was associated with lower risks of ischaemic heart disease and ischaemic stroke. Moreover, higher intakes of red meat, fish and eggs were each associated with a lower risk of intracerebral haemorrhage. Further investigation of the potential mechanisms that underlie the observed associations is required. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The CKB baseline survey and the first re-survey were supported by the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up has been supported by Wellcome grants to Oxford University (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z) and grants from the National Key Research and Development Program of China (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) and from the National Natural Science Foundation of China (91843302). The UK Medical Research Council (MC_UU_00017/1,MC_UU_12026/2 MC_U137686851), Cancer Research UK (C16077/A29186; C500/A16896) and the British Heart Foundation (CH/1996001/9454), provide core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit at Oxford University for the project. MG. Kakkoura is supported by the Wellcome Trust, Our Planet Our Health (Livestock, Environment and People - LEAP) (205212/Z/16/Z).

990Seaweed intake and risk of cardiovascular disease: the Japan Public Health Center–based Prospective (JPHC) Study

Abstract Background The minerals, vitamins, soluble dietary fibers, and flavonoids of seaweed are protective for preventing cardiovascular diseases. However, the association between seaweed intake and risk of cardiovascular disease has not been established. We examined the dietary intake of seaweed and its impact upon stroke and ischemic heart disease (IHD) risk among a Japanese study population. Methods We surveyed 40,707 men and 45,406 women from 2 large cohorts (age range: 40–69 y). Seaweed intake in the study subjects was estimated from the food frequency questionnaire at baseline (1990–1994). Stroke and IHD events were identified until the end of 2009 (Cohort I) or 2012 (Cohort II). The hazard ratios (HRs) (95% confidence intervals [CIs]) for incident cardiovascular disease (CVD) and its subtype were estimated using Cox proportional hazard models after stratification by area and adjustment for cardiovascular disease risk and dietary factors by sex. Results During 1,493,232 person-years of follow-up, 4,777 strokes and 1,204 IHD cases were identified. Among men, significant multivariable HRs (95% CIs) for almost daily consumption were seen in IHD (0.76 [0.58-0.99]; P-trend=0.04) compared to almost no seaweed consumption. Among women, such inverse associations were observed in incident IHD (0.56 [0.36-0.85]; P-trend=0.006). No significant associations were observed between seaweed intake and risk of stroke nor stroke subtypes among either men or women. Conclusions Seaweed intake has been shown to contribute to the prevention of IHD in a large Japanese cohort. Key messages Seaweed intake could be beneficial for prevention of IHD.

Cardiac reparative therapy with adipose graft transposition procedure reduces slow conduction areas in a chronic myocardial infarction swine model

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Insituto de Salud Carlos III BACKGROUND Cardiac regenerative therapy is a promising treatment for patients with ischemic heart disease, but there are some concerns on the potential increased risk of arrhythmic events following specific cell therapies. Adipose graft transposition procedure (AGTP) is a cardiac reparative therapy consisting in transposing a vascularized adipose flap from the autologous pericardium and placing it over the epicardial scar area and has demonstrated to reduce infarct size and improve the left ventricular ejection fraction in preclinical and human studies. Specific electrophysiological properties of the scar, (i.e. slow conduction velocity (CV)) have been identified as key features of ventricular tachycardia (VT) isthmuses. PURPOSE To assess the effect of the AGTP on VT inducibility and the electrophysiological properties of the post-MI scar with ultra-high density (UHD) mapping. METHODS A left circumflex artery (first marginal branch) MI was induced in 10 Landrace X Large White pigs by delivering 1-3 coils. Two weeks post-MI, all subjects underwent baseline left ventricular endocardial UHD mapping during right ventricular pacing with 64-electrode basket mapping catheter, as well as electrophysiological study (EPS) to test for VT inducibility. Following the mapping, subjects were allocated 1:1 to AGTP or sham group. UHD mapping and EPS were repeated 30 days post-treatment (6 weeks after MI). Voltage and activation maps were analyzed off-line with self-customized Paraview-based software. Voltage cut-offs of 1.5 and 0.5mV (bipolar) defined normal tissue, border zone (BZ) and dense scar, respectively, and 6.7mV for unipolar. Conduction velocity (CV) was determined for every pair of contiguous points and areas of similar CV were quantified for every 0.2m/s steps (for up to 4 m/s). RESULTS There were no differences between groups with regard of dense scar, BZ an low unipolar voltage areas. The AGTP group had a significant reduction of the size of slow CV (&amp;lt;0.2 m/s) areas, compared to the sham group in whom it increased (-4.1 ± 1.7 vs. +2.4 ± 1.6 mm2, p = 0.028)(Figure). There were no differences in the size of other ranges of CV. EPS did not induce VT in any subject at baseline, and only in 1 of the sham group at the follow-up EPS. CONCLUSIONS Cardiac reparative therapy with AGTP of post-MI scar reduced the size of slow conduction areas and could provide a protective effect against arrhythmic events in ischemic heart disease. Abstract Figure.

ALCOHOL – THE MYTH OF CARDIOVASCULAR PROTECTION

Objective: We investigated three potential errors embedded in epidemiological evidence that could mask the health effects of alcohol, i.e., by using abstainers as reference group, combining alcohol from all drink types, and including protective relationships with ischemic heart disease when assessing overall cardiovascular (CV) risk. Design and method: The UK Biobank cohort consists of over 500,000 participants that attended one of 22 assessment centers across the United Kingdom. We calculated baseline alcohol intake as grams per week and followed CV outcomes for a median 6.9 years. Results: Never drinkers were at higher risk for all CV events (P &lt; 0.0001), ischemic heart disease (P &lt; 0.0001) and cerebrovascular disease (P &lt; 0.0001). Alcohol from all drink types combined and beer/cider and spirits combined predicted CV events (both P &lt; 0.024) and cerebrovascular events (both P &lt; 0.011). Associations were stronger for beer/cider and spirits for both CV events (hazard ratio, 1.24 vs 1.08, P &lt; 0.0001) and cerebrovascular events (hazard ratio, 1.30 vs 1.15, P &lt; 0.0001). No relationships existed with ischemic heart disease (both P &gt; 0.11). Wine was protective for CV events (P = 0.008) and ischemic heart disease (P &lt; 0.0001), but not cerebrovascular events (P = 0.34). Excluding ischemic heart disease events resulted in the nullification of CV protection from wine (P = 0.95), while alcohol captured from beer/cider and spirits remained predictive (P &lt; 0.0001). Conclusions: The use of abstainers as reference group, combining of all drink types including wine when capturing alcohol intake, and embedding the protective relationship between ischemic heart disease and wine in CV risk prediction, masks the health risks associated with alcohol intake and falsely portrays alcohol as protective.

Associations of Binge Drinking With the Risks of Ischemic Heart Disease and Stroke: A Study of Pooled Norwegian Health Surveys.

Norwegian health survey data (1987–2003) were analyzed to determine if binge drinking increases the risk of incident major events from ischemic heart disease (IHD) and stroke. Among current drinkers reporting average alcohol intakes of 2.00–59.99 g/day (n = 44,476), frequent binge drinking (≥5 units at least once per month) was not associated with a greater risk of IHD (adjusted hazard ratio (HR) = 0.91, 95% confidence interval (CI): 0.76, 1.09) or stroke (adjusted HR = 0.98, 95% CI: 0.81, 1.19), in comparison with participants who reported that they never or only infrequently (less than once per month) had episodes of binge drinking. Participants with an average alcohol intake of 2.00–59.99 g/day had a lower risk of IHD in comparison with participants with very low intakes (<2.00 g/day), both among frequent binge drinkers (adjusted HR = 0.67, 95% CI: 0.56, 0.80) and among never/infrequent binge drinkers (adjusted HR = 0.75, 95% CI: 0.67, 0.84). The findings suggest that frequent binge drinking, independent of average alcohol intake, does not increase the risk of incident IHD or stroke events. However, the findings should be interpreted in light of the limitations of the study design.

The cost-effectiveness of government actions to reduce sodium intake through salt substitutes in Vietnam

BackgroundDietary sodium reduction is recommended to reduce the burden of cardiovascular disease. In Vietnam food products including salt, fish sauce and bot canh contribute to ~ 70% of dietary sodium intake. Reduced sodium versions of these products can be produced by replacing some of the sodium chloride with potassium chloride. We aimed to assess the cost-effectiveness of three alternative approaches to introducing reduced sodium products onto the market with a view to lowering population sodium intake in Vietnam.MethodsThe three salt substitution strategies included voluntary, subsidised and regulatory approaches targeting salt, fish sauce and bot canh products. Costs were modelled using the WHO-CHOICE methodology. A Markov cohort model was developed to evaluate the cost-effectiveness of each strategy versus no intervention from the government perspective. The model linked each intervention strategy to assumed changes in levels of sodium intake and then to systolic blood pressure. Changes in SBP were linked to a probability of ischaemic heart disease or stroke. The model followed people over their lifetime to assess average costs and quality adjusted life years (QALYs) gained for each strategy.ResultsThe voluntary salt substitution strategy was assumed to require no investment by government. Following ramp up (years 6+), the average annual costs for the subsidised and regulatory strategies were 21,808,968,902 ₫ (US$ 977,354) and 12,949,953,247 ₫ (US$ 580,410) respectively. Relative to no intervention, all three salt substitution strategies were found to be cost-effective. Cost savings were driven by reductions in strokes (32,595; 768,384; 2,366,480) and ischaemic heart disease (IHD) events (22,830; 537,157; 1,648,590) for the voluntary, subsidised & regulatory strategies, respectively. The voluntary strategy was least cost-effective (− 3445 ₫ US$ -0.15; 0.009 QALYs gained) followed by the subsidised strategy (− 43,189 ₫ US$ -1.86; 0.022 QALYs gained) and the regulatory strategy delivered the highest cost savings and health gains (− 243,530 ₫ US$ -10.49; 0.074 QALYs gained).ConclusionThis research shows that all three modelled salt substitution strategies would be good value for money relative to no intervention in Vietnam. The subsidised alternative would require the highest level of government investment; however the implementation costs will be exceeded by healthcare savings assuming a reasonable time horizon is considered.

Sea surface temperature variability and ischemic heart disease outcomes among older adults

Ischemic heart disease (IHD) is one of the leading causes of death worldwide. While extreme summer surface air temperatures are thought to be a risk factor for IHD, it is unclear whether large-scale climate patterns also influence this risk. This multi-national population-based study investigated the association between summer Pacific and Atlantic sea surface temperature (SST) variability and annual acute myocardial infarction (AMI) or IHD event rates among older adults residing in North America and the United Kingdom. Overall, a shift from cool to warm phase of the El Niño Southern Oscillation (ENSO) was associated with reduced AMI admissions in western Canada (adjusted rate ratio [RR] 0.89; 95% CI, 0.80–0.99), where this climate pattern predominatly forces below-normal cloud cover and precipitation during summertime, and increased AMI deaths in western United States (RR 1.09; 95% CI, 1.04–1.15), where it forces increased cloud cover and precipitation. Whereas, the Atlantic Multidecadal Oscillation (AMO) during a strong positive phase was associated with reduced AMI admissions in eastern Canada (RR 0.93; 95% CI, 0.87–0.98) and increased IHD mortality during summer months in the United Kingdom (RR 1.08; 95% CI, 1.03–1.14). These findings suggest that SST variability can be used to predict changes in cardiovascular event rates in regions that are susceptible.

Highly elevated polygenic risk scores are better predictors of myocardial infarction risk early in life than later

BackgroundSeveral polygenic risk scores (PRS) have been developed for cardiovascular risk prediction, but the additive value of including PRS together with conventional risk factors for risk prediction is questionable. This study assesses the clinical utility of including four PRS generated from 194, 46K, 1.5M, and 6M SNPs, along with conventional risk factors, to predict risk of ischemic heart disease (IHD), myocardial infarction (MI), and first MI event on or before age 50 (early MI).MethodsA cross-validated logistic regression (LR) algorithm was trained either on ~ 440K European ancestry individuals from the UK Biobank (UKB), or the full UKB population, including as features different combinations of conventional established-at-birth risk factors (ancestry, sex) and risk factors that are non-fixed over an individual’s lifespan (age, BMI, hypertension, hyperlipidemia, diabetes, smoking, family history), with and without also including PRS. The algorithm was trained separately with IHD, MI, and early MI as prediction labels.ResultsWhen LR was trained using risk factors established-at-birth, adding the four PRS significantly improved the area under the curve (AUC) for IHD (0.62 to 0.67) and MI (0.67 to 0.73), as well as for early MI (0.70 to 0.79). When LR was trained using all risk factors, adding the four PRS only resulted in a significantly higher disease prevalence in the 98th and 99th percentiles of both the IHD and MI scores.ConclusionsPRS improve cardiovascular risk stratification early in life when knowledge of later-life risk factors is unavailable. However, by middle age, when many risk factors are known, the improvement attributed to PRS is marginal for the general population.

Trends in Ischaemic Heart Disease in Australia, 2001–2015: A Comparison of Urban and Rural Populations

Ischaemic heart disease (IHD) is a major source of disease burden worldwide. Recent trends show incidence is declining but it is unclear whether the trends are similar in urban and rural populations. This study examines the trends of IHD events (i.e. hospitalisations and deaths) in New South Wales, Australia by rurality. This was a retrospective analysis of linked administrative data for hospitalisation and death records across NSW between 2001 and 2015. Participants were NSW residents aged 15-105 years who died or were hospitalised with a principal diagnosis of IHD. The main outcome measures were annual age-standardised mortality and hospitalisations for IHD by calendar year and rurality. Between 2001 and 2015, age-standardised annual IHD hospitalisations declined in urban areas from 587 to 260 and in rural areas from 766 to 395 per 100,000 people. The annual decline in hospitalisations was greater in urban than rural areas, with Annual Percentage Change (APC) of-5.6% (95% CI,-6.1%,-5.0%) and-4.5% (95% CI,-5.0%,-4.0%), respectively (p=0.012). Ischaemic heart disease mortality declined at a similar rate in urban and rural regions (APC-7.6% and-6.7% per annum, p=0.28). Absolute inequalities in IHD deaths persisted until 2015 when there were 49 (urban) and 70 (rural) IHD deaths per 100,000 people. Ischaemic heart disease hospitalisations and mortality have declined considerably between 2001 and 2015 in both rural and urban areas, yet inequalities persist, suggesting more intensive preventive efforts are required to further reduce the burden of IHD in rural populations.

Long-Term PM2.5 Exposure and Risks of Ischemic Heart Disease and Stroke Events: Review and Meta-Analysis.

BackgroundFine particulate matter <2.5 µm in diameter (PM2.5) has known effects on cardiovascular morbidity and mortality. However, no study has quantified and compared the risks of incident myocardial infarction, incident stroke, ischemic heart disease (IHD) mortality, and cerebrovascular mortality in relation to long‐term PM2.5 exposure.Methods and ResultsWe sought to quantitatively summarize studies of long‐term PM2.5 exposure and risk of IHD and stroke events by conducting a review and meta‐analysis of studies published by December 31, 2019. The main outcomes were myocardial infarction, stroke, IHD mortality, and cerebrovascular mortality. Random effects meta‐analyses were used to estimate the combined risk of each outcome among studies. We reviewed 69 studies and included 42 studies in the meta‐analyses. In meta‐analyses, we found that a 10‐µg/m3 increase in long‐term PM2.5 exposure was associated with an increased risk of 23% for IHD mortality (95% CI, 15%–31%), 24% for cerebrovascular mortality (95% CI, 13%–36%), 13% for incident stroke (95% CI, 11%–15%), and 8% for incident myocardial infarction (95% CI, −1% to 18%). There were an insufficient number of studies of recurrent stroke and recurrent myocardial infarction to conduct meta‐analyses.ConclusionsLong‐term PM2.5 exposure is associated with increased risks of IHD mortality, cerebrovascular mortality, and incident stroke. The relationship with incident myocardial infarction is suggestive of increased risk but not conclusive. More research is needed to understand the relationship with recurrent events.

Abstract 16935: Cardiovascular Disease in Head Neck Squamous Cell Carcinoma Patients - A Case-Control Study Using Electronic Medical Records Data

Introduction: Cancer survivors have higher rates of cardiovascular disease (CVD) compared to age-adjusted general population. However, traditional CVD risk factors alone do not fully explain increased CVD risk in cancer patients. Cancer-related factors like cancer site, stage and chemotherapy may also contribute to CVD. Despite increase in head neck squamous cell carcinoma (HNSCC) cases in recent years, little is known about CVD risk in HNSCC patients. We aim to assess association of traditional risk factors and cancer-related factors with CVD in HNSCC patients. Methods: Electronic medical records data of 2391 HNSCC patients diagnosed between 2012-2018 at the UAB O’Neal Comprehensive Cancer Center, were included. ICD-9/10 codes were used to identify HNSCC patients, CVD cases and traditional risk factors. CVD cases were defined as those with composite events of ischemic heart disease and/ or heart failure; controls were without any CVD diagnosis. Cancer site, stage and treatment were included. Logistic regression [OR(95%CI)] was used to assess association of risk factors with CVD, adjusting for age, race, and gender. Results: HNSCC patients were mostly white (82.7%), male (74.7%) and had Stage III/IV cancer (46.6%). Oral cavity was the most common cancer site (32.9%), followed by oropharynx (31.7%); 55.4% patients had hypertension, 23.0% had dyslipidemia, and 16.1% had diabetes. CVD was diagnosed in 16.1% patients, who were more likely to be older [median age 67.0 vs 60.0 years, p&lt;0.0001]. In the multivariable model, hypertension [2.08(1.54-2.80)], diabetes [2.03(1.52-2.70)] and dyslipidemia [2.36(1.82-3.07)] were associated with CVD. Smoking status was not associated. Association of cancer stage with CVD varied by cancer site. Stage III/IV oropharynx cancer patients had lower odds of CVD than stage I/II oropharynx patients [0.38(0.30-0.92)]. No association with cancer stage was observed in oral cavity patients. Compared to chemotherapy, surgery [0.85(0.63-1.14)] and other treatments {0.61(0.41-0.89)] had lower odds of CVD. Conclusions: Traditional CVD risk factors remain associated with CVD in HNSCC patients. In addition, cancer-related factors (oropharynx cancer, advanced cancer stage and chemotherapy) are also associated with CVD.

Estimated health benefits, costs, and cost-effectiveness of eliminating industrial trans-fatty acids in Australia: A modelling study.

trans-fatty acids (TFAs) are a well-known risk factor of ischemic heart disease (IHD). In Australia, the highest TFA intake is concentrated to the most socioeconomically disadvantaged groups. Elimination of industrial TFA (iTFA) from the Australian food supply could result in reduced IHD mortality and morbidity while improving health equity. However, such legislation could lead to additional costs for both government and food industry. Thus, we assessed the potential cost-effectiveness, health gains, and effects on health equality of an iTFA ban from the Australian food supply. Markov cohort models were used to estimate the impact on IHD burden and health equity, as well as the cost-effectiveness of a national ban of iTFA in Australia. Intake of TFA was assessed using the 2011-2012 Australian National Nutrition and Physical Activity Survey. The IHD burden attributable to TFA was calculated by comparing the current level of TFA intake to a counterfactual setting where consumption was lowered to a theoretical minimum distribution with a mean of 0.5% energy per day (corresponding to TFA intake only from nonindustrial sources, e.g., dairy foods). Policy costs, avoided IHD events and deaths, health-adjusted life years (HALYs) gained, and changes in IHD-related healthcare costs saved were estimated over 10 years and lifetime of the adult Australian population. Cost-effectiveness was assessed by calculation of incremental cost-effectiveness ratios (ICERs) using net policy cost and HALYs gained. Health benefits and healthcare cost changes were also assessed in subgroups based on socioeconomic status, defined by Socio-Economic Indexes for Areas (SEIFA) quintile, and remoteness. Compared to a base case of no ban and current TFA intakes, elimination of iTFA was estimated to prevent 2,294 (95% uncertainty interval [UI]: 1,765; 2,851) IHD deaths and 9,931 (95% UI: 8,429; 11,532) IHD events over the first 10 years. The greatest health benefits were accrued to the most socioeconomically disadvantaged quintiles and among Australians living outside of major cities. The intervention was estimated to be cost saving (net cost <0 AUD) or cost-effective (i.e., ICER < AUD 169,361/HALY) regardless of the time horizon, with ICERs of 1,073 (95% UI: dominant; 3,503) and 1,956 (95% UI: 1,010; 2,750) AUD/HALY over 10 years and lifetime, respectively. Findings were robust across several sensitivity analyses. Key limitations of the study include the lack of recent data of TFA intake and the small sample sizes used to estimate intakes in subgroups. As with all simulation models, our study does not prove that a ban of iTFA will prevent IHD, rather, it provides the best quantitative estimates and corresponding uncertainty of a potential effect in the absence of stronger direct evidence. Our model estimates that a ban of iTFAs could avert substantial numbers of IHD events and deaths in Australia and would likely be a highly cost-effective strategy to reduce social-economic and urban-rural inequalities in health. These findings suggest that elimination of iTFA can cost-effectively improve health and health equality even in countries with low iTFA intake.

State of the coronary arteries and assessment of the role of hormone replacement therapy in patients with coronary heart disease against the background of primary manifest hypothyroidism

Aim To study features of coronary damage and incidence of different types of acute coronary syndrome (ACS) in history associated with primary symptomatic hypothyroidism in patients with ischemic heart disease (IHD) and possible associations of replacement hormonal therapy with lipidogram indexes.Material and methods This retrospective study included 344 patients with IHD and functional class I-III stable angina (ССS, 1976). Of them 100 patients had primary symptomatic hypothyroidism and 244 had no hypothyroidism. Coronary angiography was performed for all patients included into this study. Routine laboratory, instrumental and clinical indexes were analyzed. Hypothyroidism was confirmed by levels of thyrotropic hormone, free triiodothyronine, and thyroxine. Comparative analysis was performed for the incidence of ACS types in history, types of coronary injury, and laboratory, instrumental and clinical indexes with assessment of potential interrelations. Statistically significant results were reported. Type of data distribution was evaluated with the Kolmogorov-Smirnov test. Quantitative data with normal (Gaussian) distribution were presented as mean (M) and standard deviation (SD). Data with attributes of non-normal distribution were presented as median (Me) with maximum and minimum values (min; max). Statistical significance of differences between means was assessed with the Mann-Whitney test. Logistic regression analysis was used in parallel for evaluating dependence of a quantitative variable on values of two or more quantitative or qualitative variables (factors). Significance level for testing of statistical hypotheses was р&lt;0.05.Results Incidence of ST segment elevation ACS (STEACS) was significantly higher in IHD patients with hypothyroidism than in the group without hypothyroidism (61.6 and 35.6 %, р=0.03) and also with three-vessel coronary artery disease (60.6 and 30.6 %, р=0.001). In the IHD group with hypothyroidism, levels of total cholesterol, triglycerides, and low- and very low-density lipoproteins were significantly increased compared to the respective values in patients without hypothyroidism (р&lt;0.0001). An inverse correlation was found between lipidogram indexes and L-thyroxine (р&lt;0.0001).Conclusion The incidence of STEACS associated with primary symptomatic hypothyroidism in history was significantly higher in the patient group with IHD on the background of primary symptomatic hypothyroidism compared to the comparison group. Also, the incidence of three-vessel coronary disease was significantly greater than in the IHD patient group without hypothyroidism. A significant association was found between the replacement hormonal therapy and the best lipidogram indexes. The authors suggested that the key factor for prevention of adverse cardiovascular events in IHD with hypothyroidism is achieving control of clinical manifestations of hypothyroidism with replacement hormonal therapy.

Estimation of dynamic models of recurrent events with censored data

Summary In this paper, we consider estimation of dynamic models of recurrent events (event histories) in continuous time using censored data. We develop maximum simulated likelihood estimators where missing data are integrated out using Monte Carlo and importance sampling methods. We allow for random effects and integrate out this unobserved heterogeneity using a quadrature rule. In Monte Carlo experiments, we find that maximum simulated likelihood estimation is practically feasible and performs better than both listwise deletion and auxiliary modelling of initial conditions. In an empirical application, we study ischaemic heart disease events for male Maoris in New Zealand.

Mortality and Major Cardiovascular Events in Ischemic Heart Disease Are Associated with Nonthyroidal Illness and Thyroid Hormone Deficiency

Mortality and Major Cardiovascular Events in Ischemic Heart Disease Are Associated with Nonthyroidal Illness and Thyroid Hormone Deficiency