Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank

BackgroundCardiac magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied.ObjectivesThe associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up.MethodsNative T1-mapping was performed in 1 midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5-T scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, nonischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models.ResultsHigher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10^-9) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10^-4). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10^-4), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10^-11), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10^-5), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310).ConclusionsThis large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.     

Genetic Risk Score for Coronary Disease Identifies Predispositions to Cardiovascular and Noncardiovascular Diseases

BackgroundThe taxonomy of cardiovascular (CV) diseases is divided into a broad spectrum of clinical entities. Many such diseases coincide in specific patient groups and suggest shared predisposition.ObjectivesThis study focused on coronary artery disease (CAD) and investigated the genetic relationship to CV and non-CV diseases with reported CAD comorbidity.MethodsThis study examined 425,196 UK Biobank participants to determine a genetic risk score (GRS) based on 300 CAD associated variants (CAD-GRS). This score was associated with 22 traits, including risk factors, diseases secondary to CAD, as well as comorbid and non-CV conditions. Sensitivity analyses were performed in individuals free from CAD or stable angina diagnosis.ResultsHypercholesterolemia (odds ratio [OR]: 1.27; 95% CI: 1.26 to 1.29) and hypertension (OR: 1.11; 95% CI: 1.10 to 1.12) were strongly associated with the CAD-GRS, which indicated that the score contained variants predisposing to these conditions. However, the CAD-GRS was also significant in patients with CAD who were free of CAD risk factors (OR: 1.37; 95% CI: 1.30 to 1.44). The study observed significant associations between the CAD-GRS and peripheral arterial disease (OR: 1.28; 95% CI: 1.23 to 1.32), abdominal aortic aneurysms (OR: 1.28; 95% CI: 1.20 to 1.37), and stroke (OR: 1.08; 95% CI: 1.05 to 1.10), which remained significant in sensitivity analyses that suggested shared genetic predisposition. The score was also associated with heart failure (OR: 1.25; 95% CI: 1.22 to 1.29), atrial fibrillation (OR: 1.08; 95% CI: 1.05 to 1.10), and premature death (OR: 1.04; 95% CI: 1.02 to 1.06). These associations were abolished in sensitivity analyses that indicated that they were secondary to prevalent CAD. Finally, an inverse association was observed between the score and migraine headaches (OR: 0.94; 95% CI: 0.93 to 0.96).ConclusionsA wide spectrum of CV conditions, including premature death, might develop consecutively or in parallel with CAD for the same genetic roots. In conditions like heart failure, the study found evidence that the CAD-GRS could be used to stratify patients with no or limited genetic overlap with CAD risk. Increased genetic predisposition to CAD was inversely associated with migraine headaches.     

Blood Pressure Variation and Subclinical Brain Disease

BackgroundLarge blood pressure (BP) variability may contribute to stroke and dementia, but the mechanisms are largely unknown.ObjectivesThis study investigated the association of BP variation, considering its magnitude and direction, with the presence and progression of subclinical brain disease in the general population.MethodsThis study included 2,348 participants age ≥55 years from a prospective cohort study. BP was measured at each visit every 3 to 4 years from 1990 onward. Brain magnetic resonance imaging (MRI) was performed at all visits from 2005 onward. The authors primarily assessed variation as the absolute difference in BP divided by the mean over 2 sequential visits for both systolic BP (SBP) and diastolic BP (DBP), and further assessed the direction of the variation. The authors investigated the multivariate-adjusted associations of BP variation with subsequent measurements of MRI markers of cerebral small vessel disease, brain tissue volumes, and white matter microstructural integrity. Longitudinal changes in these markers also were assessed.ResultsA large SBP variation (top vs. bottom tertiles), measured on average 7 years preceding brain MRI, was associated with higher odds of having severe white matter hyperintensities (WMH) (odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.21 to 1.43), lacunes (OR: 1.25; 95% CI: 1.04 to 1.48), and microbleeds (OR: 1.16; 95% CI: 1.03 to 1.31). Similarly, this variation was associated with smaller total brain volume and worse white matter microstructural integrity (all p < 0.001). A large SBP variation was also associated with the progression of WMH (rate ratio [RR]: 1.14; 95% CI: 1.02 to 1.27). Higher burdens of these brain imaging markers were observed with both large rises and falls in SBP. Similar findings were observed for DBP variation.ConclusionsElevated BP variation was associated with a wide range of subclinical brain structural changes, including MRI markers of cerebral small vessel disease, smaller brain tissue volumes, and worse white matter microstructural integrity. These subclinical brain changes could be the underlying mechanisms linking BP variation to dementia and stroke.     

Myocardial Contractile Mechanics in Ischemic Mitral Regurgitation: Multicenter Data Using Stress Perfusion Cardiovascular Magnetic Resonance

BackgroundLeft ventricular (LV) ischemia has been variably associated with functional mitral regurgitation (FMR). Determinants of FMR in patients with ischemia are poorly understood.ObjectivesThis study sought to test whether contractile mechanics in ischemic myocardium underlying the mitral valve have an impact on likelihood of FMR.MethodsVasodilator stress perfusion cardiac magnetic resonance was performed in patients with coronary artery disease (CAD) at multiple centers. FMR severity was confirmed quantitatively via core lab analysis. To test relationship of contractile mechanics with ischemic FMR, regional wall motion and strain were assessed in patients with inducible ischemia and minimal (≤5% LV myocardium, nontransmural) infarction.ResultsA total of 2,647 patients with CAD were studied; 34% had FMR (7% moderate or greater). FMR severity increased with presence (P < 0.001) and extent (P = 0.01) of subpapillary ischemia: patients with moderate or greater FMR had more subpapillary ischemia (odds ratio [OR]: 1.13 per 10% LV; 95% CI: 1.05-1.21; P = 0.001) independent of ischemia in remote regions (P = NS); moderate or greater FMR prevalence increased stepwise with extent of ischemia and infarction in subpapillary myocardium (P < 0.001); stronger associations between FMR and infarction paralleled greater wall motion scores in infarct-affected territories. Among patients with inducible ischemia and minimal infarction (n = 532), wall motion and radial strain analysis showed impaired subpapillary contractile mechanics to associate with moderate or greater FMR (P < 0.05) independent of remote regions (P = NS). Conversely, subpapillary ischemia without contractile dysfunction did not augment FMR likelihood. Mitral and interpapillary dimensions increased with subpapillary radial strain impairment; each remodeling parameter associated with impaired subpapillary strain (P < 0.05) independent of remote strain (P = NS). Subpapillary radial strain (OR: 1.13 per 5% [95% CI: 1.02-1.25]; P = 0.02) and mitral tenting area (OR: 1.05 per 10 mm² [95% CI: 1.00-1.10]; P = 0.04) were associated with moderate or greater FMR controlling for global remodeling represented by LV end-systolic volume (P = NS): when substituting sphericity for LV volume, moderate or greater FMR remained independently associated with subpapillary radial strain impairment (OR: 1.22 per 5% [95% CI: 1.02-1.47]; P = 0.03).ConclusionsAmong patients with CAD and ischemia, FMR severity and adverse mitral apparatus remodeling increase in proportion to contractile dysfunction underlying the mitral valve.     

Heterogenous Distribution of Risk for Cardiovascular Disease Events in Patients With Stable Ischemic Heart Disease

ObjectivesThe authors sought to assess the distribution of 5-year risk of cardiovascular disease (CVD) events (myocardial infarction, revascularizations, ischemic stroke) and death among symptomatic patients with varying degrees of coronary artery disease (CAD) ascertained from computed tomography angiography (CTA).BackgroundCTA is used increasingly as the first-line test for evaluating patients with symptoms suggestive of CAD. This creates the daily clinical challenge of best using the information available from CTA to guide appropriate downstream allocation of preventive treatments.MethodsAmong 21,275 patients from the Western Denmark Heart Registry, the authors developed a model predicting 5-year risk for CVD and death based on traditional risk factors and CAD severity. Only events occurring >90 days after CTA were included.ResultsDuring a median follow-up of 4.2 years, 1,295 CVD events and deaths occurred. The median 5-year risk for events was 4% (interquartile range: 3% to 8%), and ranged from <5% to >50% in individual patients. The degree of CAD severity was the strongest risk factor; however, traditional risk factors also contributed significantly to risk. Thus, risk distributions in patients with varying degree of CAD overlapped considerably, and patients with extensive nonobstructive CAD could have higher estimated risk than patients with obstructive CAD (stenosis >50%). Among patients with obstructive CAD, 12% had 5-year risk <10% whereas 24% had risk >20%. A similar large overlap in risk was found when revascularizations were excluded from the endpoint.ConclusionsThe 5-year risk for CVD events and death varies substantially in symptomatic patients undergoing CTA, even in the presence of obstructive CAD. These results provide support for individual risk assessment to improve potential benefit when allocating preventive therapies following CTA.     

Association between statin adherence and the risk of stroke among South Korean adults with hyperlipidemia

Background and aimsThe effectiveness of statins commonly used to prevent stroke may depend on adherence to treatment. We examined the association between statin adherence and stroke risk among South Korean adults with hyperlipidemia.Methods and resultsThe data of 128,052 and 129,390 participants with hyperlipidemia for the purpose of studying the risks of ischemic and hemorrhagic stroke, respectively, were collected from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2013. Participants were divided into groups according to statin adherence, calculated as the proportion of days covered (PDC; poor, moderate, good). The risk of ischemic and hemorrhagic stroke were analyzed using a Cox proportional hazards model. Individuals with poor PDC exhibited higher risks of ischemic and hemorrhagic stroke than those with good PDC (ischemic stroke: hazard ratio [HR] = 1.09, 95% confidence interval [CI] = 1.03–1.15, hemorrhagic stroke: HR = 1.37, 95% CI = 1.22–1.54). Women with poor PDC were at higher risk of ischemic stroke than those with good PDC (HR = 1.17, 95% CI = 1.09–1.26), while men with poor PDC exhibited a higher risk of hemorrhagic stroke than those with good PDC (HR = 1.55, 95% CI = 1.27–1.90). Individuals with disabilities who had poor PDC were at higher risk of ischemic stroke than those with good PDC (HR = 1.55, 95% CI = 1.24–1.93).ConclusionsWe detected a significant association between statin adherence and ischemic and hemorrhagic stroke risk. Therefore, hyperlipidemia patients should adhere to statin treatment; such interventions are required to reduce the stroke risk.     

Triglyceride-Rich Lipoprotein Cholesterol,Small Dense LDL Cholesterol,and Incident Cardiovascular Disease

BackgroundElevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populations are mostly limited to coronary heart disease.ObjectivesThe purpose of this study was to prospectively evaluate whether triglyceride-rich lipoprotein cholesterol (TRL-C) and small-dense low-density lipoprotein cholesterol (sdLDL-C) concentrations associate with composite and individual incident cardiovascular disease (CVD) outcomes including myocardial infarction (MI), ischemic stroke (IS), and peripheral artery disease (PAD).MethodsIn a prospective case-cohort study within the Women’s Health Study, TRL-C and sdLDL-C (mg/dl) were directly measured in baseline blood specimens of case subjects (n = 480) and the reference subcohort (n = 496). Risk associations were evaluated for total CVD (MI, IS, PAD, and CVD death), coronary and cerebrovascular disease (MI, IS, CVD death), and individual outcomes (MI, IS, and PAD). Models were adjusted for traditional risk factors, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein.ResultsThe risk of both composite outcomes significantly increased across quartiles of TRL-C and sdLDL-C. TRL-C was significantly associated with MI and PAD (MI hazard ratio [HR]_Q4: 3.05 [95% confidence interval (CI): 1.46 to 6.39]; p_trend = 0.002; PAD HR_Q4: 2.58 [95% CI: 1.18 to 5.63]; p_trend = 0.019), whereas sdLDL-C was significantly associated with MI alone (HR_Q4: 3.71 [95% CI: 1.59 to 8.63]; p_trend < 0.001). Both markers weakly associated with IS. Association patterns were similar for continuous exposures and, for TRL-C, among subjects with low atherogenic particle concentrations (apolipoprotein B <100 mg/dl).ConclusionsTRL-C strongly associates with future MI and PAD events, whereas sdLDL-C strongly associates with MI alone. These findings signal that the cholesterol content of TRLs and sdLDL influence atherogenesis independently of low-density lipoprotein cholesterol, and high sensitivity C-reactive protein, with potentially different potency across vascular beds. (Women’s Health Study; NCT00000479)     

Effect of body mass index trajectory on lifetime risk of cardiovascular disease in a Chinese population: A cohort study

Background and aimsThe longitudinal trajectories of body mass index (BMI) can reflect the pattern of BMI changes. Lifetime risk quantifies the cumulative risk of developing a disease over the remaining life of a person. We aimed to identify the trajectory of BMI and explore its association with cardiovascular disease (CVD) in the Chinese population.Methods and resultsA total of 68,603 participants with a mean age of 55.46 years were included from the Kailuan cohort in Tangshan, China, who were free of CVD and cancer and with repeated measurements of BMI from 2006 to 2010. A latent mixture model was used to identify BMI trajectories. An improved Kaplan-Meier estimator was used to predict the lifetime risk of CVD according to BMI trajectories. During a median follow-up of 7.0 years, 3325 participants developed CVD. Five BMI trajectories were identified at three index ages (35, 45, and 55) respectively. For index age 35 years, compared with the stable low-normal weight group (22.7% [95% CI, 20.0%–25.4%]), the stable high-normal weight (27.6% [25.6%–29.5%]), stable overweight (29.4% [27.4%–31.4%]), stable-low obesity (32.8% [30.0%–35.5%]), and stable-high obesity (38.9% [33.3%–44.5%]) groups had a higher lifetime risk of CVD (P < 0.05). We observed similar patterns for stroke and myocardial infarction. Similarly, the lifetime risk of CVD was higher in the long-term overweight and obese groups at 45 and 55 index ages.ConclusionsLong-term overweight and obesity were associated with an increased lifetime risk of CVD. Our findings could assist in predicting the population burden of CVD.     

Mechanical ventilation for acute exacerbation of fibrosing interstitial lung diseases

BackgroundAcute exacerbation of fibrosing interstitial lung diseases, including idiopathic pulmonary fibrosis, is associated with poor prognosis. Accordingly, tracheal intubation and invasive mechanical ventilation are generally avoided in such patients. However, the efficacy of invasive mechanical ventilation for acute exacerbation of fibrosing interstitial lung diseases remains unclear. Therefore, we aimed to investigate the clinical course of patients with acute exacerbation of fibrosing interstitial lung diseases who were treated with invasive mechanical ventilation.MethodsWe retrospectively analyzed 28 patients with acute exacerbation of fibrosing interstitial lung diseases who underwent invasive mechanical ventilation at our hospital.ResultsOf the 28 included patients (20 men, 8 women; mean age, 70.6 years), 13 (46.4%) were discharged alive and 15 died. Ten patients (35.7%) had idiopathic pulmonary fibrosis. Univariate analysis revealed that longer survival was significantly associated with lower partial pressure of arterial carbon dioxide (hazard ratio [HR] 1.04 [1.01–1.07]; p = 0.002) and higher pH (HR 0.0002 [0–0.02] levels; p = 0.0003) and less severe general status according to the Acute Physiology and Chronic Health Evaluation II score (HR 1.13 [1.03–1.22]; p = 0.006) at the time of mechanical ventilation initiation. In addition, the univariate analysis indicated that patients without long-term oxygen therapy use had significantly longer survival (HR 4.35 [1.51–12.52]; p = 0.006).ConclusionsInvasive mechanical ventilation may effectively treat acute exacerbation of fibrosing interstitial lung diseases if good ventilation and general conditions can be maintained.     

Deep-Learning for Epicardial Adipose Tissue Assessment With Computed Tomography: Implications for Cardiovascular Risk Prediction

BackgroundEpicardial adipose tissue (EAT) volume is a marker of visceral obesity that can be measured in coronary computed tomography angiograms (CCTA). The clinical value of integrating this measurement in routine CCTA interpretation has not been documented.ObjectivesThis study sought to develop a deep-learning network for automated quantification of EAT volume from CCTA, test it in patients who are technically challenging, and validate its prognostic value in routine clinical care.MethodsThe deep-learning network was trained and validated to autosegment EAT volume in 3,720 CCTA scans from the ORFAN (Oxford Risk Factors and Noninvasive Imaging Study) cohort. The model was tested in patients with challenging anatomy and scan artifacts and applied to a longitudinal cohort of 253 patients post-cardiac surgery and 1,558 patients from the SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, to investigate its prognostic value.ResultsExternal validation of the deep-learning network yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT volume was associated with coronary artery disease (odds ratio [OR] per SD increase in EAT volume: 1.13 [95% CI: 1.04-1.30]; P = 0.01), and atrial fibrillation (OR: 1.25 [95% CI: 1.08-1.40]; P = 0.03), after correction for risk factors (including body mass index). EAT volume predicted all-cause mortality (HR per SD: 1.28 [95% CI: 1.10-1.37]; P = 0.02), myocardial infarction (HR: 1.26 [95% CI:1.09-1.38]; P = 0.001), and stroke (HR: 1.20 [95% CI: 1.09-1.38]; P = 0.02) independently of risk factors in SCOT-HEART (5-year follow-up). It also predicted in-hospital (HR: 2.67 [95% CI: 1.26-3.73]; P ≤ 0.01) and long-term post–cardiac surgery atrial fibrillation (7-year follow-up; HR: 2.14 [95% CI: 1.19-2.97]; P ≤ 0.01).ConclusionsAutomated assessment of EAT volume is possible in CCTA, including in patients who are technically challenging; it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification.     

Effect of metabolic control on recurrent major adverse cardiovascular events and cardiovascular mortality in patients with premature coronary artery disease: Results of the Genetics of Atherosclerotic Disease study

Background and aimsCoronary artery disease (CAD) is the leading cause of death around the world, and its rate of presentation is increasing at young ages. Despite the evidence that secondary prevention in CAD reduces the risk of recurrent major adverse cardiovascular events (MACE), no studies have analyzed the composite control of blood pressure, lipids, and glucose control in premature CAD.Methods and resultsThis was a real-world prospective cohort study of patients with premature CAD. The composite control in blood pressure <140/80 mmHg, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and Hemoglobin A1c <8% was considered as metabolic control. The primary endpoint was the occurrence of non-fatal and fatal MACE. The data included 1042 patients with premature CAD. The mean age of the patients was 54.1 ± 8.1 years, 18.5% were women, and had a median follow-up of 59.1 ± 11.8 months. Of them, 7% had non-fatal MACE, and 4% had a fatal MACE. Overall, 21.3% achieved metabolic control, and 3.0% did not achieve any target. Cox regression analysis showed that percutaneous coronary intervention (Hazzard ratio = 1.883 [95% CI, 1.131–3.136]), C-reactive protein (1.046 [1.020–1.073]), blood pressure >140/90 mmHg (2.686 [1.506–4.791]), fibrates (2.032 [1.160–3.562]), calcium channel blockers (2.082 [1.158–3.744]) had greater risk to present a recurrent non-fatal MACE; whereas familial history of premature CAD (2.419 [1.240–4.721]), heart failure (2.139 [1.032–4.433]), LDL-C >70 mg/dL (4.594 [1.401–15.069]), and diuretics (3.328 [1.677–6.605]) were associated with cardiovascular mortality.ConclusionsThe composite goal achievement in lipids, blood pressure and glucose, reduced the risk for recurrent MACE in 80%.     

Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance

ObjectivesThis study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans.BackgroundExperimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake.MethodsThe study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo.ResultsMedian plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m² vs. 82 ± 15 ml/m²; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP.ConclusionsOnly primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910).     

The PROMISE Minimal Risk Score Improves Risk Classification of Symptomatic Patients With Suspected CAD

BackgroundGuidelines for evaluating patients with suspected coronary artery disease (CAD) recommend pretest probability (PTP) estimation but provide no clear recommendations regarding diagnostic testing in patients with >5% to 15% risk of obstructive CAD. The diagnostic and prognostic value of PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) minimal risk score (PMRS) calculation in this patient group is unknown.ObjectivesThis work aims to improve the evaluation of stable patients with suspected CAD by using the PMRS, which identifies patients at minimal risk of CAD and events in patients with >5% to 15% PTP of obstructive CAD.MethodsGreater than 5% to 15% PTP patients from 2 large clinical trials were used for subcohort derivation: PROMISE (N = 10,003) and Dan-NICAD (Danish study of Non-Invasive Testing in Coronary Artery Disease) (N = 3,252). First, the PMRS cutoff associated with a prevalence of obstructive CAD ≤5% was determined in the >5% to 15% PTP PROMISE core lab computed tomographic angiography patients (discovery cohort: n = 2,191). This cutoff was validated for obstructive CAD in >5% to 15% PTP Dan-NICAD patients (CAD validation cohort: n = 1,386) and for prognostic impact on death and myocardial infarction in >5% to 15% PTP PROMISE non–core lab computed tomographic angiography patients (prognosis validation cohort: n = 2,753).ResultsIn the discovery cohort, a CAD prevalence of ≤5% was found at a PMRS of ≥34%. In the CAD validation cohort, this cutoff down-classified 442 (31.9%) of >5% to 15% PTP patients into the low PTP group (CAD ≤5%); the prevalence of obstructive CAD in down-classified patients was 3.2% compared to 7.1% in non–down-classified patients. A PMRS ≥34% was nonsignificantly associated with a lower risk of myocardial infarction and death in the prognosis validation cohort (HR: 0.58 [95% CI: 0.29-1.18]; P = 0.13).ConclusionsFor evaluating patients with suspected CAD, a combined use of traditional PTP and the PMRS correctly down-classified one-third of >5% to 15% PTP patients into a group with very low prevalence of obstructive CAD and adverse events. The proposed strategy may improve risk stratification and help reduce unneeded diagnostic testing.     

Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement: Meta-Analysis of Kaplan-Meier–Derived Individual Patient Data

BackgroundIt remains controversial whether prosthesis-patient mismatch (PPM) (in general considered moderate if indexed effective orifice area is 0.65-0.85 cm²/m² and severe when <0.65 cm²/m²) affects the outcomes after transcatheter aortic valve replacement (TAVR).ObjectivesThe purpose of this study is to evaluate the time-varying effects and association of PPM with the risk of overall mortality.MethodsStudy-level meta-analysis of reconstructed time-to-event data from Kaplan-Meier curves of studies published by December 30, 2021.ResultsIn total, 23 studies met our eligibility criteria and included a total of 81,969 patients included in the Kaplan-Meier curves (19,612 with PPM and 62,357 without PPM). Patients with moderate/severe PPM had a significantly higher risk of mortality compared with those without PPM (HR: 1.09 [95% CI: 1.04-1.14]; P < 0.001). In the first 30 months after the procedure, mortality rates were significantly higher in the moderate/severe PPM group (HR: 1.1 [95% CI: 1.05-1.16]; P < 0.001). In contrast, the landmark analysis beyond 30 months yielded a reversal of the HR (0.83 [95% CI: 0.68-1.01]; P = 0.064), but without statistical significance. In the sensitivity analysis, although the authors observed that severe PPM showed higher risk of mortality in comparison with no PPM (HR: 1.25 [95% CI: 1.16-1.36]; P < 0.001), they did not observe a statistically significant difference for mortality between moderate PPM and no PPM (HR: 1.03 [95% CI: 0.96-1.10]; P = 0.398).ConclusionsSevere PPM, but not moderate PPM, was associated with higher risk of mortality following TAVR. These results provide support to implementation of preventive strategies to avoid severe PPM following TAVR.     

Smoking and alcohol consumption influence the risk of cardiovascular diseases in Korean adults with elevated blood pressure

Background and aimsCardiovascular disease (CVD) and hypertension are the main causes of global death. We aimed to investigate the independent and combined effects of smoking and alcohol consumption on CVD risk among Koreans with elevated blood pressure (BP).Methods and resultsAdults aged 20–65 years with elevated BP and without pre-existing CVDs were selected from the National Health Insurance Service-National Sample Cohort version 2.0. We followed up 59,391 men and 35,253 women between 2009 and 2015. The association of CVD incidence with smoking pack-years and alcohol consumption was investigated using the multivariate Cox proportional hazard model. Among women, smokers (10.1–20.0 pack-years) and alcohol drinkers (≥30.0 g/day) had higher CVD risks (hazard ratio [HR] = 1.15, 95% confidence intervals [CI] 1.06–1.25, HR = 1.06, 95% CI 1.00–1.12, respectively) compared to each referent group. However, men who smoked exhibited an increased CVD risk only with pack-years >20.0 (HR = 1.09, 1.03–1.14 and HR = 1.18, 1.11–1.26 for smokers with 20.1–30.0 and ≥ 30.1 pack-years, respectively) compared to nonsmokers. In the combined groups of those smoking and consuming alcohol, only nonsmoking men consuming alcohol 1.0–29.9 g/day had a lower CVD risk than did nonsmoking, nondrinking men (HR = 0.90, 0.83–0.97). Women smoking 1.0-10.0 pack-years and consuming alcohol ≥30.0 g/day had a higher CVD risk (HR = 1.25, 1.11–1.41) than nonsmoking and nondrinking women.ConclusionSmoking and alcohol consumption, independently and jointly, were associated with CVD risk in men and women. Women had a greater CVD risk than did men among Korean adults with elevated BP.     

Morphine and Cardiovascular Outcomes Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Undergoing Coronary Angiography

BackgroundMechanistic studies have shown that morphine blunts the antiplatelet effects of oral adenosine diphosphate receptor blockers. However, the clinical relevance of this interaction is controversial.ObjectivesThis study sought to explore the association between morphine and ischemic events in 5,438 patients treated with concomitant clopidogrel presenting with non-ST-segment elevation acute coronary syndromes (NSTEACS) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome) trial. Patients not treated with clopidogrel (n = 3,462) were used as negative controls.MethodsEndpoints were the composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout at 96 h (4-way endpoint) and the composite of death or MI at 30 days.ResultsIn patients treated with clopidogrel, morphine use was associated with higher rates of the 4-way endpoint at 96 h (adjusted odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.04 to 1.87; p = 0.026). There was a trend for higher rates of death or MI at 30 days (adjusted OR: 1.29; 95% CI: 0.98 to 1.70; p = 0.072), driven by events in the first 48 h (adjusted hazard ratio: 1.54; 95% CI: 1.07 to 2.23; p = 0.021). In patients not treated with clopidogrel, morphine was not associated with either the 4-way endpoint at 96 h (adjusted OR: 1.05; 95% CI: 0.74 to 1.49; p = 0.79; p_interaction = 0.36 ) or death or MI at 30 days (adjusted OR: 1.07; 95% CI: 0.77 to 1.48; p = 0.70; p_interaction = 0.46).ConclusionsWhen used concomitantly with clopidogrel pre-treatment, morphine was associated with higher rates of ischemic events in patients with NSTEACS. (EARLY ACS: Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome; NCT00089895)     

Association of NT-ProBNP,Blood Pressure,and Cardiovascular Events: The ARIC Study

BackgroundAlthough intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.ObjectivesThis study examined whether N-terminal pro–B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.MethodsParticipants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors.ResultsThere were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg.ConclusionsElevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.     

Statin use and the risk of CVD events,stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis

AimsConsidering the lack of evidence on statin use and the risk of cardiovascular disease (CVD) in patients with diabetes in primary and secondary prevention, this study aimed to evaluate the effect of statin use in individuals with diabetes for primary and secondary prevention.Data synthesisThe MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials databases were searched. We included studies that assessed the effect of statin use in individuals with diabetes for at least 1 year. The outcomes included CVD, all-cause mortality, and stroke. A total of 24 studies including 2,152,137 patients with diabetes were included in the meta-analysis. Compared with statin non-users, patients who received statins showed a lower risk of CVD events (primary prevention: risk ratio [RR] = 0.80, 95% confidence interval [CI] 0.69–0.94, P = 0.006; secondary prevention: RR = 0.75, 95% CI 0.65–0.87, P < 0.0001). No association was observed between statin and non-statin users and the risk of all-cause mortality. The pooled results also revealed that statin use reduced the risk of ischemic stroke in patients with diabetes (primary prevention: RR = 0.83, 95% CI 0.70–0.97, P = 0.020; secondary prevention: RR = 0.74, 95% CI 0.63–0.85, P < 0.0001).ConclusionsStatin use significantly reduced the risk of CVD events and stroke, but not all-cause mortality, in individuals with diabetes undergoing both primary and secondary prevention. More data are required to verify the effects of statins in patients with diabetes.Systematic review registrationPROSPERO CRD42021281132.     

Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging

BackgroundIschemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging–derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.ObjectivesThe authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.MethodsBrain age was estimated in subjects with prevalent IHD (n = 1,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n = 35,237).ResultsPrevalent IHD was linked to significantly accelerated brain aging (P < 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13 [95% CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.ConclusionsPrevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.     

Remnant cholesterol as a risk factor for all-cause and cardiovascular mortality in incident peritoneal dialysis patients

Background and aimsRemnant cholesterol (RC) adversely contributes to cardiovascular disease (CVD) and overall survival in various diseases. However, its role in CVD outcomes and all-cause mortality in patients undergoing peritoneal dialysis (PD) is limited. Therefore, we aimed to investigate the association between RC and all-cause and CVD mortality in patients undergoing PD.Methods and resultsBased on lipid profiles recorded using standard laboratory procedures, fasting RC levels were calculated in 2710 incident patients undergoing PD who were enrolled between January 2006 and December 2017 and followed up until December 2018. Patients were divided into four groups according to the quartile distribution of baseline RC levels (Q1: <0.40 mmol/L, Q2: 0.40 to <0.64 mmol/L, Q3: 0.64 to <1.03 mmol/L, and Q4: ≥1.03 mmol/L). Associations between RC and CVD and all-cause mortality were evaluated using multivariable Cox models. During the median follow-up period of 35.4 months (interquartile range, 20.9–57.2 months), 820 deaths were recorded, of which 438 were CVD-related. Smoothing plots showed non-linear relationships between RC and adverse outcomes. The risks of all-cause and CVD mortality increased progressively through the quartiles (log-rank, p < 0.001). Using adjusted proportional hazard models, a comparison of the highest (Q4) to lowest (Q1) quartiles revealed significant increases in the hazard ratio (HR) for all-cause mortality (HR 1.95 [95% confidence interval (CI), 1.51–2.51]) and CVD mortality risk (HR 2.60 [95% CI, 1.80–3.75]).ConclusionAn increased RC level was independently associated with all-cause and CVD mortality in patients undergoing PD, suggesting that RC was important clinically and required further research.