Myocardial Infarction Hazard Ratio Research Articles

Increased cardiovascular risks and mortality in prurigo nodularis: a global cohort study

BackgroundPrurigo nodularis (PN) presents with intensely itchy hard nodules. Despite being limited to the skin, PN was noted to be associated with systemic diseases including diabetes and chronic renal failure. In previous smaller retrospective studies, several cardiac and vascular diseases were found more frequently in patients with PN. However, small cohort sizes, partially discrepant outcomes, missing data, and incomplete risk assessment limit these findings. MethodsElectronic health records (EHR)s of 64,801 patients (59.44% females) with PN and an equal sized propensity-matched control group were retrieved. In these cohorts, the risks to develop cardiac and vascular diseases and mortality following diagnosis of PN were determined. Sub-analyses included stratification for sex, ethnicity, and treatments. FindingsPN was associated with a higher risk for a broad range of acute cardiac events including heart failure and myocardial infarction. For example, the hazard ratio of myocardial infarction was 1.11 (95%-CI: 1.041-1.184, p=0.0015) following PN diagnosis. Also, all-cause mortality was higher in patients with PN. Further, chronic vascular as well as structural heart diseases, e.g., peripheral arterial disease, chronic ischaemic heart disease and valval disorders were found more frequently following a PN diagnosis. Risks were more pronounced in white and female patients. Having established an increased risk for death and cardiovascular disease, we next addressed if dupilumab that has been recently licenced for use in this indication can modulate these risks. The risk of death but not of any cardiovascular disease was slightly reduced in patients with PN treated with dupilumab as opposed to those treated with systemic therapies other than dupilumab. The study is limited by retrospective data collection and reliance on ICD10-disease classification. InterpretationPN is associated with higher mortality and an increased risk for the development of a wide range of cardiac and vascular diseases. Health care professionals should take this into account when managing patients with PN. FundingThis work was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft and the State of Schleswig-Holstein.

Influence of Low-Density Lipoprotein Cholesterol Levels on NSAID-Associated Cardiovascular Risks After Myocardial Infarction: A Population-Based Cohort Study.

To examine whether low-density lipoprotein cholesterol (LDL-C) levels influence the cardiovascular risk associated with non-aspirin non-steroidal anti-inflammatory drug (NSAID) use after myocardial infarction (MI). Using Danish health registries, we conducted a population-based cohort study of all adult patients with first-time MI during 2010-2020 with an LDL-C value before discharge. Based on the latest LDL-C value, we categorized patients into a low and a high LDL-C group (<3.0 vs ≥3.0 mmol/L). We used time varying Cox regression to compute hazard ratios (HRs) with 95% confidence intervals of the association between NSAID use and a major adverse cardiovascular event (MACE: recurrent MI, ischemic stroke, and all-cause death). We followed 50,573 patients for a median of 3.1 years. While exposed, 521 patients experienced a MACE: 312 in the low LDL-C group and 209 in the high LDL-C group. The HRs for MACE comparing NSAID use with non-use were 1.21 (1.11-1.32) overall, 1.19 (1.06-1.33) in the low LDL-C group, and 1.23 (1.07-1.41) in the high LDL-group. The HRs for recurrent MI and ischemic stroke were comparable between the LDL-C subgroups. The HRs for all-cause death were 1.22 (1.07-1.39) in the low LDL-C group and 1.54 (1.30-1.83) in the high LDL-C group. Changing the cut-off value for LDL-C to 1.8 and 1.4 mmol/L showed consistent results. In patients with MI, LDL-C levels did not influence the increased risk of MACE associated with NSAID use, but might influence the association between NSAID use and all-cause death.

Risk of myocardial infarction among pigeon breeders: A follow-up study

Pigeon breeders are exposed to high levels of fine particulate organic matter in the pigeon lofts. A total of 6,704 pigeon breeders and their 1:30 sex and age-matched referents from the general Danish population were followed from 1980 or first year of membership in the Danish Racing Pigeon Association, until first event of myocardial infarction, emigration, death, or end of study, on December 31, 2013. Information on outcomes and covariates was obtained by record linkage with national registers. Stratified Cox regression models estimated the hazard ratio of myocardial infarction, adjusted for occupation and residence at the start of follow-up. Compared with referents, pigeon breeders had an adjusted hazard ratio of 1.14 (95% CI: 1.05–1.22) for myocardial infarction. Exposure to pigeon-derived organic dust may increase the risk of myocardial infarction, but this finding needs to be corroborated.

Association Between Premature Menopause and Cardiovascular Diseases and All-Cause Mortality in Korean Women.

Background Mortality from cardiovascular diseases in Asian populations is considerable. Menopause is a risk-enhancing factor for cardiovascular disease, but it is unclear whether menopause is an independent risk factor for cardiovascular disease and mortality in Asian women. Methods and Results A total of 1 159 405 postmenopausal women, who had participated in the health examinations of the Korean National Health Insurance Service in 2009, were analyzed, and their reproductive histories were taken. A multivariable Cox proportional hazard model assessed the hazard ratios (HRs) of myocardial infarction (MI), ischemic stroke, and all-cause mortality, according to the history of premature menopause and age at menopause. After an average 10-year follow-up, there were 31 606, 45 052, and 77 680 new cases of MI, ischemic stroke, and all-cause mortality, respectively. The women with premature menopause exhibited increased risks of MI (HR, 1.40 [95% CI, 1.31-1.50]), ischemic stroke (HR, 1.24 [95% CI, 1.17-1.31]), and all-cause mortality (HR, 1.19 [95% CI, 1.14-1.24]) when compared with women with menopause aged ≥50 years. The highest risk was evident with menopause between the ages of 30 and 34 years (HR for MI, 1.52 [95% CI, 1.30-1.78]; HR for ischemic stroke, 1.29 [95% CI, 1.12-1.48]; HR for all-cause mortality, 1.33 [95% CI, 1.20-1.47]) when compared with women with menopause aged ≥50 years. Conclusions Earlier age at menopause was associated with increased risks for MI, ischemic stroke, and all-cause mortality. Future guidelines and risk assessment tools should consider menopause as an independent risk factor of cardiovascular disease in Korean women.

Increased risk of myocardial infarction in amyotrophic lateral sclerosis: A nationwide cohort study in South Korea

BackgroundThe risk of myocardial infarction (MI), the major form of CVD, in amyotrophic lateral sclerosis (ALS) is currently unknown. We investigated the risk of MI in ALS and analyzed the effect of ALS-related physical disability on the risk of MI using the Korean National Health Insurance Service database. MethodsA total of 659 ALS patients and 10,927 non-ALS participants were finally selected between January 1, 2011, and December 31, 2015. A Cox hazard regression model was used to examine the hazard ratios (HRs) for MI in ALS after adjustment for potential confounders. ResultsThe incidence rate of MI was 26.2 per 1000 person-years, and the adjusted HR (aHR) for MI in ALS patients was 10.6 (95% confidence interval [CI] 7.2–15.4) compared with the controls. ALS patients who developed physical disability had an even higher risk of MI (aHR 18.6, 95% CI 11.5–30.0) compared with those who did not develop disability (aHR 7.4, 95% CI 4.6–11.9). The increased risk of MI was more prominent in female subjects than in male subjects (aHR 17.8, 95% CI 10.8–29.4 vs. aHR 6.9, 95% CI 4.1–11.6, P for interaction 0.006) and in obese subjects than in non-obese subjects (aHR 17.8, 95% CI 10.5–30.1 vs. aHR 7.9, 95% CI 4.9–12.8, P for interaction 0.018). ConclusionsOur findings suggest that the risk of MI is high in ALS patients compared with a control population, and the risk is more prominent in those who develop physical disability, or who are female or obese.

Age and sex differences in the risk of cardiovascular diseases by chronic kidney disease in a general Japanese population.

The risk of cardiovascular diseases (CVD) by chronic kidney disease (CKD) stratified by age and sex has not been examined in detail in rural Japanese populations. Therefore, we herein investigated the long-term risk of CVD by CKD and performed an age- and sex-stratified risk analysis. We examined 5163 subjects who underwent health screening between 1992 and 1995 with calculated eGFR and follow-up information on CVD events. The mean follow-up period was 10years. We analyzed the incidences of CVD events, including stroke and myocardial infarction (MI). We compared the risk of CVD between subjects with and without CKD using a Cox proportional hazards model adjusted for well-known CVD confounding factors.The total number of CVD events was 175. The hazard ratios (HRs) for all events, stroke, MI, and sudden death by CKD relative to non-CKD were 1.18 (95% C.I.:0.83-1.68), 0.96 (0.63-1.46), 3.02 (1.2-7.62), and 1.29 (0.43-3.87), respectively. HRs for MI were 7.24 in subjects < 65years and 1.65 in those ≥ 65years. HRs for MI by sex were 3.55 in men and 2.09 in women. A younger age and men sex were identified as independent risk factors for the risk of MI in the presence of CKD. These results suggest that among CKD patients, the management of a younger age group and men will effectively prevent MI.

Associations between Body Mass Index, Waist Circumference, and Myocardial Infarction in Older Adults Aged over 75 Years: A Population-Based Cohort Study.

Background and Objectives: Body mass index (BMI) is widely used as a standard screening method for obesity and an indicator of related diseases. However, its inability to distinguish between lean body mass and body fat limits its utility. This limitation may be more prominent in older populations, wherein age-related sarcopenia and increased visceral fat due to the redistribution of adipose tissue may preclude a precise estimation of obesity. Many studies suggest that waist circumference (WC) is more strongly related to obesity-related diseases. There are also different opinions on whether the obesity paradox is real or a result of confusing interpretations. This study seeks to determine the association between myocardial infarction (MI), BMI, and WC in older adults and to determine if BMI and WC can reliably predict the risk of cardiovascular disease. Materials and Methods: We conducted a cohort study of older Korean adults aged over 75 years registered in the National Health Insurance System Senior database. Results: The results from the analysis using model 5, which was adjusted for each study variable, showed that the lower the BMI, the higher the hazard ratio (HR) of MI and vice versa. On the other hand, groups with lower than normal WC showed lower HR; even if it was higher, the difference was not statistically significant. Those with abdominal obesity tended to have an increased HR of MI. Conclusions: This study found that HR for MI has a negative relationship with BMI, whereas it has a positive relationship with WC. Furthermore, WC is a more appropriate indicator for predicting the risk of MI in the older population.

Remnant cholesterol and the risk of cardiovascular disease in type 2 diabetes: a nationwide longitudinal cohort study

BackgroundElevated remnant cholesterol (remnant-C) is considered a risk factor for cardiovascular disease (CVD); however, whether this notion applies to the East Asian population with type 2 diabetes (T2D) has not been established. This study investigated the association between remnant-C concentrations and the risk of CVD in Korean patients with T2D.MethodsBy using the Korean National Health Insurance Service database, 1,956,452 patients with T2D and without atherosclerotic CVD who underwent regular health checks between 2009 and 2012 were included. Cox regression analyses were conducted to assess the association between remnant-C concentrations and incident CVD comprising myocardial infarction (MI) and ischemic stroke.ResultsIn total, 50,120 (2.56%) cases of MI and 73,231 (3.74%) cases of ischemic strokes occurred during a median follow-up of 8.1 years. The adjusted hazard ratios for MI and stroke in the highest remnant-C quartile were 1.281 (95% confidence interval [CIs], 1.249–1.314) for MI and 1.22 (1.195–1.247) for ischemic stroke, compared to those in the lowest quartiles. The results were similar, based on stratified analysis by age, sex, use of statin or fibrate, and levels of other cholesterol. The increased risk of CVD in the highest remnant-C quartile was profound in patients who had a longer T2D duration. A remnant-C concentration ≥ 30 mg/dL differentiated patients who were at a higher risk of CVD, compared to patients with a lower concentrations, regardless of whether LDL-C levels were or were not on target at ≤ 100 mg/dL.ConclusionIn Korean patients with T2D, remnant-C was associated with CVD, independent of the LDL-C level or other conventional CVD risk factors. Our finding confirmed evidence of the causal role of remnant-C on CVD, as a residual risk of CVD, in East Asian patients with T2D.

Association of metabolic comorbidity with myocardial infarction in individuals with a family history of cardiovascular disease: a prospective cohort study

BackgroundThe association between metabolic comorbidity and myocardial infarction (MI) among individuals with a family history of cardiovascular disease (CVD) is yet to be elucidated. We aimed to examine the combined effects of metabolic comorbidities, including diabetes mellitus, hypertension, and dyslipidemia, with a family history of CVD in first-degree on the risk of incident MI.MethodsThis cohort study consisted of 81,803 participants aged 40–89 years without a previous history of MI at baseline from the Korean Genome and Epidemiology Study. We performed Cox proportional hazard regression analysis to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for MI and early-onset MI risk associated with metabolic comorbidity in individuals with a family history of CVD.ResultsDuring a median follow-up of 5 years, 1,075 and 479 cases of total and early-onset MI were reported, respectively. According to the disease score, among individuals who had a positive family history of CVD, the HRs for MI were 1.92 (95% CI: 1.47–2.51) in individuals with one disease, 2.75 (95% CI: 2.09–3.61) in those with two diseases, and 3.74 (95% CI: 2.45–5.71) in those with three diseases at baseline compared to individuals without a family history of CVD and metabolic diseases. Similarly, an increase of the disease score among individuals with a positive family history of CVD was associated with an increase in early-onset MI risk.ConclusionMetabolic comorbidity was significantly associated with an increased risk of MI among individuals with a family history of CVD.

Incorporation of Retinal Arteriolosclerosis into Risk Stratification of Blood Pressure Category According to the 2017 ACC/AHA Blood Pressure Guideline

Aim: We investigated whether retinal arteriolosclerosis (RA) could be used for cardiovascular disease (CVD) risk stratification of individuals categorized according to the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) Blood Pressure (BP) guideline. Methods: We studied 291,522 participants without a history of CVD and not taking any BP-lowering medications from the JMDC Claims Database. RA was defined as Keith–Wagener–Barker system grade ≥ 1. Each participant was classified into one of the six groups: (1) normal or elevated BP without RA, (2) normal or elevated BP with RA, (3) stage 1 hypertension without RA, (4) stage 1 hypertension with RA, (5) stage 2 hypertension without RA, and (6) stage 2 hypertension with RA. Results: Median (interquartile range) age was 46 (40–53) years, and 141,397 (48.5%) of the participants were men. During a mean follow-up of 1,223±830 days, 527 myocardial infarction (MI), 5,718 angina pectoris, 2,890 stroke, and 5,375 heart failure (HF) events occurred. Multivariable Cox regression analyses revealed that the risk of CVD increased with BP category, and this association was pronounced by the presence of RA. Compared with normal or elevated BP without RA, the hazard ratios (HRs) for MI (HR 1.17, 95% CI 0.93–1.47) were higher in stage 1 hypertension without RA. The HRs for MI further increased in stage 1 hypertension with RA (1.86 [1.17–2.95]). This association was present in stroke and HF. Conclusion: Incorporation of the assessment for RA may facilitate the CVD risk stratification of people classified based on the 2017 ACC/AHA BP guideline, particularly for those categorized in stage 1 hypertension.

MO445: Implications of Cardiac Biomarkers in Patients With Renal Insufficiency on Probability of Coronary Angiography and Subsequent Cardiovascular Outcomes

Abstract BACKGROUND AND AIMS Renal insufficiency is associated with an increased risk of cardiovascular morbidity and mortality. Although cardiac troponin remains essential marker for the diagnosis of myocardial injury in the general population, the diagnostic utility remains uncertain in patients with renal insufficiency. We examined the likelihood of coronary angiography and the risk of myocardial infarction after hospitalization with elevated troponin levels in patients with renal insufficiency. METHOD Based on data from multiple Danish nationwide healthcare registries, all hospitalized patients with elevated troponin I or T were identified between 2000 and 2021. Patients with age &amp;lt; 18 years, estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2 and patients hospitalized with myocardial infarction &amp;lt; 30 days prior to the index were excluded. Renal function was calculated based on preceding plasma creatinine using the CKD-EPI equation. The probability of being referred for coronary angiography was computed across strata of renal insufficiency [eGFR (mL/min/1.73m2) 59–45, 44–30, 29–15 and &amp;lt; 15, respectively] based on multiple Cox regression calculating hazard ratios for 30-day likelihood of coronary angiography, with subsequent comparison of cumulative risk and hazard ratios for myocardial infarction using the Aalen-Johansen estimator and multiple Cox regression, respectively. RESULTS In total 57 044 patients were included in the study. Patients were predominantly male (53%, n = 30 222), with a median age of 81 years (IQR 74–87 years). eGFR strata (%): 59–45: 46.8%; 44–30: 30.6%; 29–15; 15.6%; &amp;lt;15: 7.%. Cardiovascular comorbidity was substantial; 47.1% of patients had a history of hypertension, 20.5%% of patients had a history of heart failure, 26.6% of patients had a history of diabetes and 25.3% of patients had a history of ischemic heart disease. Hazard ratios for 30-day likelihood of coronary angiography were 1.26 [95% confidence interval (CI) 1.10–1.44] for eGFR 15–29 mL/min/1.73m2, 2.00 (95% CI 1.77–2.25) for eGFR 30–44 mL/min/1.73m2 and 2.95 (95% CI 2.63–3.31) for eGFR 45–59 mL/min/1.73m2, using eGFR &amp;lt; 15 as reference. Subsequent cumulative risk of myocardial infarction is shown in Figure 1. Hazard ratios for risk of myocardial infarction were 0.86 (95% CI 0.71–1.03) for eGFR 15–29 mL/min/1.73m2, 0.58 (95% CI 0.49–0.69) for eGFR 30–44 mL/min/1.73m2 and 0.49 (95% CI 0.42–0.58) for eGFR 45–59 mL/min/1.73m2, using eGFR &amp;lt; 15 as reference. CONCLUSION In patients with elevated troponin levels, renal insufficiency is associated with an incrementally decreased probability of coronary angiography despite a graded proportional increase in the risk of subsequent myocardial infarction.

Association of High-Density Lipoprotein Cholesterol Phenotypes with the Risk of Cardiovascular Diseases and Mortality: A Cohort Study in Korea.

Background We investigated whether low high-density lipoprotein cholesterol (HDL-C) and isolated and non-isolated low HDL-C levels are associated with the risk of cardiovascular diseases and all-cause mortality among Korean adults.Methods We included 8,665,841 individuals aged ≥20 years who had undergone a health examination provided by the Korean National Health Insurance Service (NHIS) in 2009 and were followed up until the end of 2018. The hazard ratios (HRs) and 95% confidence intervals (CIs) for study outcomes were calculated using multivariable Cox proportional hazard regression analysis.Results During the 8.2 years of mean follow-up, myocardial infarction (MI), stroke, and all-cause mortality occurred in 81,431, 110,996, and 244,309 individuals, respectively. After adjusting for confounding variables (model 3), individuals with low HDL-C and lower HDL quartiles were associated with significantly increased risks of all three outcomes, compared to those with normal HDL-C and highest HDL-C quartile (all P<0.001), respectively. HRs for incident MI (1.28; 95% CI, 1.26 to 1.30), stroke (1.13; 95% CI, 1.11 to 1.15), and all-cause mortality (1.07; 95% CI, 1.05 to 1.08) increased in the non-isolated low HDL-C group compared to the normal HDL-C group. Isolated low HDL-C also showed an increase in the HRs of incident stroke (1.06; 95% CI, 1.04 to 1.08) and all-cause mortality (1.30; 95% CI, 1.28 to 1.32).Conclusion Low HDL-C and non-isolated low HDL-C were associated with increased risk of MI, stroke, and all-cause mortality, and isolated low HDL-C was associated with incident stroke and all-cause mortality risk.

The long-term effect of exposure to respirable particulate matter on the incidence of myocardial infarction: a systematic review and meta-analysis study

Although several studies have investigated the long-term association of respirable particulate matter (PM ≤ 10µm) with the incidence of myocardial infarction (MI), this association is inconclusive or even contradictory. This systematic review and meta-analysis study aimed to quantify the long-term effect of exposure to respirable PM on the incidence of MI. To find relevant publications, online databases, including Scopus, PubMed, and Web of Science, were searched on October 10, 2021. A random-effect model was used to calculate the pooled hazard ratio (HR) and 95% confidence interval (95% CI) of MI across studies. Heterogeneity was presented with reporting I2 index. Of 4591 records found in the primary searching, the number of 24 prospective cohort studies with more than 70 million participants was included. The pooled HR (95% CI) of MI per 1µg/m3 increment of respirable PM was estimated as 1.01 (1.00, 1.01). Subgroup analyses according to aerodynamic diameter of PM showed an only significant stronger risk of MI per 1µg/m3 increase in PM with aerodynamic diameter < 2.5µm (HR = 1.01, 95% CI = 1.00, 1.01). No sex difference was found in the association of respirable PM with MI incidence. There was only a significant association among studies defined MI as ICD-10: I21 code (HR = 1.01, 95% CI = 1.00, 1.01) and studies defined MI as ICD-10: I21-22 (HR = 1.02, 95% CI = 1.00, 1.04). No significant publication bias was observed across studies. In conclusion, this study confirms a significant association between long-term exposure to respirable PM air pollution and development of MI.

Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort: A cohort study.

BackgroundElevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop.Methods and findingsIn the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25–84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan–Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case–control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study.ConclusionsAn imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines.

Polygenic Risk Score for Coronary Artery Disease Improves the Prediction of Early-Onset Myocardial Infarction and Mortality in Men.

Several risk factors for coronary artery disease (CAD) have been described, some of which are genetically determined. The use of a polygenic risk score (PRS) could improve CAD risk assessment, but predictive accuracy according to age and sex is not well established. A PRSCAD including the weighted effects of >1.14 million single nucleotide polymorphisms associated with CAD was calculated in UK Biobank (n=408 422), using LDpred. Cox regressions were performed, stratified by age quartiles and sex, for incident myocardial infarction (MI) and mortality, with a median follow-up of 11.0 years. Improvement in risk prediction of MI was assessed by comparing PRSCAD to the pooled cohort equation with categorical net reclassification index using a 2% threshold (NRI0.02) and continuous NRI (NRI>0). From 7746 incident MI cases and 393 725 controls, hazard ratio for MI reached 1.53 (95% CI, 1.49-1.56; P=2.69×10-296) per SD increase of PRSCAD. PRSCAD was significantly associated with MI in both sexes, with a stronger association in men (interaction P=0.002), particularly in those aged between 40 and 51 years (hazard ratio, 2.00 [95% CI, 1.86-2.16], P=1.93×10-72). This group showed the highest reclassification improvement, mainly driven by the up-classification of cases (NRI0.02, 0.199 [95% CI, 0.157-0.248] and NRI>0, 0.602 [95% CI, 0.525-0.683]). From 23 982 deaths, hazard ratio for mortality was 1.08 (95% CI, 1.06-1.09; P=5.46×10-30) per SD increase of PRSCAD, with a stronger association in men (interaction P=1.60×10-6). Our PRSCAD predicts MI incidence and all-cause mortality, especially in men aged between 40 and 51 years. PRS could optimize the identification and management of individuals at risk for CAD.

The long-term risk for myocardial infarction or stroke after proton pump inhibitor therapy (2008-2018).

Proton pump inhibitors (PPIs) are well tolerated in the short term but have recently been associated with increased long-term cardiovascular risk in observational studies. To evaluate long-term risks of myocardial infarction (MI) and ischaemic stroke (IS) associated with PPI vs H2 -receptor antagonist (H2 RA) therapy in adults without pre-existing cardiovascular or cerebrovascular disease METHODS: Using administrative claims data (2008-2018), we emulated a target trial comparing MI and IS risks in new users of PPIs vs H2 RAs. Treatment was identified using dispensed prescriptions. MI and IS were defined using hospital discharge codes. Inverse probability weighting was used to adjust for confounding, and Cox models to estimate hazard ratios (HRs). Survival curves were estimated using weighted Kaplan-Meier estimators. We identified 1143948 new users of PPIs and 36229 new users of H2 RAs who were free of prevalent cardiovascular or cerebrovascular disease. The mean follow-up time was 6.2years for PPI initiators and 5.3years for H2 RA initiators. After 10years, the HRs for MI and IS were 0.96 (95% confidence interval (CI): 0.80-1.16) and 0.98 (95% CI: 0.89-1.08), respectively. This analysis of claims data of a large German health insurer did not provide evidence that PPI therapy increased the risk of MI or IS in the first decade after treatment initiation.

The effect of adjustment to register-based and questionnaire-based covariates on the association between air pollution and cardiometabolic disease

ObjectiveRecent studies on air pollution and disease have been based on millions of participants within a region or country, relying entirely on register-based confounder adjustment. We aimed to investigate the effects of increasing adjustment for register- and questionnaire-based covariates on the association between air pollution and cardiometabolic diseases. MethodsIn a population-based cohort of 246,766 eligible participants randomly selected across Denmark in 2010 and 2013 and followed up until December 31, 2017, we identified 3,247 myocardial infarction (MI) cases, 4,166 stroke cases and 6,366 type 2 diabetes cases. Based on historical address-information, we calculated 5-year time-weighted exposure to PM2.5 and NO2 modelled using a validated air pollution model. We used Cox proportional hazards models to calculate hazard ratios (HR) with increasing adjustment for a number of individual- and area-level register-based covariates as well as lifestyle covariates assessed through questionnaires. ResultsWe found that a 5 μg/m3 higher PM2.5 was associated with HRs (95% CI) for MI, stroke and diabetes, of respectively, 1.18 (0.91–1.52), 1.11 (0.88–1.40) and 1.24 (1.03–1.50) in the fully adjusted models. For all three diseases, adjustment for either individual-level, area-level or lifestyle covariates, or combinations of these resulted in higher HRs compared to HRs adjusted only for age, sex and calendar-year, most marked for MI and diabetes. Further adjustment for lifestyle in models with full register-based individual- and area-level adjustment resulted in only minor changes in HRs for all three diseases. ConclusionsOur findings suggest that in studies of air pollution and cardiometabolic disease, which use an adjustment strategy with a broad range of register-based socioeconomic variables, there is no effect on risk estimates from subsequent lifestyle adjustment.

Replacement of potatoes with other vegetables and risk of myocardial infarction in the Danish Diet, Cancer and Health cohort.

Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29142 women and 26029 men aged 50-64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazard ratios (HR) with 95 % CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13·6 years of follow-up, 656 female and 1694 male cases were identified. Among women, the adjusted HR for MI was 1·02 (95 % CI 0·93, 1·13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0·93 (95 % CI 0·77, 1·13) for replacement of potatoes with fruiting vegetables and 0·91 (95 % CI 0·77, 1·07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.

Country of birth and mortality risk in hypertension with and without diabetes: the Swedish primary care cardiovascular database.

Hypertension and diabetes are common and are both associated with high cardiovascular morbidity and mortality. We aimed to investigate associations between mortality risk and country of birth among hypertensive individuals in primary care with and without concomitant diabetes, which has not been studied previously. In addition, we aimed to study the corresponding risks of myocardial infarction and ischemic stroke. This observational cohort study of 62 557 individuals with hypertension diagnosed 2001-2008 in the Swedish Primary Care Cardiovascular Database assessed mortality by the Swedish Cause of Death Register, and myocardial infarction and ischemic stroke by the National Patient Register. Cox regression models were used to estimate study outcome hazard ratios by country of birth and time updated diabetes status, with adjustments for multiple confounders. During follow-up time without diabetes using Swedish-born as reference, adjusted mortality hazard ratios per country of birth category were Finland: 1.26 (95% confidence interval 1.15-1.38), high-income European countries: 0.84 (0.74-0.95), low-income European countries: 0.84 (0.71-1.00) and non-European countries: 0.65 (0.56-0.76). The corresponding adjusted mortality hazard ratios during follow-up time with diabetes were high-income European countries: 0.78 (0.63-0.98), low-income European countries: 0.74 (0.57-0.96) and non-European countries: 0.56 (0.44-0.71). During follow-up without diabetes, the corresponding adjusted hazard ratio of myocardial infarction was increased for Finland: 1.16 (1.01-1.34), whereas the results for ischemic stroke were inconclusive. In Sweden, hypertensive immigrants (with the exception for Finnish-born) with and without diabetes have a mortality advantage, as compared to Swedish-born.

VLDL Cholesterol Accounts for One-Half of the Risk of Myocardial Infarction Associated With apoB-Containing Lipoproteins

BackgroundPlasma apolipoprotein B (apoB) is a composite measure of all apoB-containing lipoproteins causing atherosclerotic cardiovascular disease; however, it is unclear which fraction of risk is explained by cholesterol and triglycerides, respectively, in very low-density lipoproteins (VLDLs). ObjectivesThe authors tested the hypothesis that VLDL cholesterol and triglycerides each explain part of the myocardial infarction risk from apoB-containing lipoproteins. MethodsNested within 109,751 individuals from the Copenhagen General Population Study, the authors examined 25,480 subjects free of lipid-lowering therapy and myocardial infarction at study entry. All had measurements of plasma apoB (quantitating number of apoB-containing lipoproteins) and cholesterol and triglyceride content of VLDL, intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs). ResultsDuring a median 11 years of follow-up, 1,816 were diagnosed with myocardial infarction. Per 1-mmol/l higher levels, multivariable-adjusted hazard ratios for myocardial infarction were 2.07 (95% confidence interval [CI]: 1.81 to 2.36) for VLDL cholesterol, 1.19 (95% CI: 1.14 to 1.25) for VLDL triglycerides, 5.38 (95% CI: 3.73 to 7.75) for IDL cholesterol, and 1.86 (95% CI: 1.62 to 2.14) for LDL cholesterol. Per 1-g/l higher plasma apoB, the corresponding value was 2.21 (95% CI: 1.90 to 2.58). In a step-up Cox regression, risk factors for myocardial infarction entered by importance as VLDL cholesterol, systolic blood pressure, smoking, and IDL + LDL cholesterol, whereas VLDL triglycerides did not enter the model. VLDL cholesterol explained 50% and IDL + LDL cholesterol 29% of the risk of myocardial infarction from apoB-containing lipoproteins, whereas VLDL triglycerides did not explain risk. ConclusionsVLDL cholesterol explained one-half of the myocardial infarction risk from elevated apoB-containing lipoproteins, whereas VLDL triglycerides did not explain risk.