Mendelian Randomization Focused Analysis of Vitamin D on the Secondary Prevention of Ischemic Stroke.

BACKGROUND AND PURPOSE: Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction. METHODS: Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study-identified genetic variants of Vit-D mechanistic pathways (rs2060793, rs4588, and rs7041; F statistic, 73; P<0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach. RESULTS: In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; P=0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48-0.81]; P<0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35-0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42-0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30-0.81]). CONCLUSIONS: Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI.

Single-chamber leadless pacemaker for atrial synchronous or ventricular pacing.

Leadless pacing is a major breakthrough in the management of bradyarrhythmia. Results of initial clinical trials that have demonstrated a significant reduction in acute and long-term pacing-related complications have been confirmed by real-world experience in a broader spectrum of patients. Nonetheless current use of a leadless pacemaker is hampered by its limited atrial sensing and pacing capability, as well as battery life-span and retrievability. We review the current clinical outcome data, indications and contraindications, implantation and retrieval techniques, synchronous ventricular pacing, and other clinical considerations. We also provide an overview of the latest advancements in leadless pacing technology including device-to-device communication and energy harvesting technology.

Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention of Recurrent Cardiovascular Events in a Real-World Cohort of Post-Acute Myocardial Infarction Patients.

BACKGROUND: Patients who survive myocardial infarction (MI) are at risk of recurrent cardiovascular (CV) events. This study stratified post-MI patients for risk of recurrent CV events using the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P). Methods and Results: This was an observational study that applied TRS 2°P to a consecutive cohort of post-MI patients. The primary outcome was a composite endpoint of CV death, non-fatal MI, and non-fatal ischemic stroke. A total of 1,688 post-MI patients (70.3±13.6 years; male, 63.1%) were enrolled. After a mean follow-up of 41.5±34.4 months, 405 patients (24.0%) had developed a primary outcome (9.3%/year) consisting of 278 CV deaths, 134 non-fatal MI, and 33 non-fatal strokes. TRS 2°P was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P 0 was 1.0%, and increased progressively to 39.9% for those with TRS 2°P ≥6 (HR, 27.6; 95% CI: 9.87-77.39, P<0.001). The diagnostic sensitivity of TRS 2°P for the primary composite endpoint was 76.3% (95% CI: 72.1-80.5%). Similar associations were also observed between TRS 2°P and CV death and non-fatal MI, but not non-fatal ischemic stroke. CONCLUSIONS: TRS 2°P reliably stratified post-MI patients for risk of future CV events.

Prognostic implications of statin intolerance in stable coronary artery disease patients with different levels of high-sensitive troponin.

BACKGROUND: The prognostic implication of statin in tolerance (SI) in those with stable CAD remains unclear. We hypothesized that SI is of higher prognostic significance in stable CAD patients with elevated high-sensitive cardiac troponin I (hs-cTnI). METHODS: A total of 952 stable CAD patients from the prospective Hong Kong CAD study who had complete clinical data, biomarker measurements and who were prescribed statin therapy were studied. RESULTS: We identified 13 (1.4%) and 125 (13.1%) patients with complete and partial SI, respectively. At baseline, patients with SI were more likely to have diabetes mellitus and a higher hs-cTnI level, but no difference in LDL-C level compared with those without SI. After 51 months of follow-up, patients with SI had a higher mean LDL-C level than those without SI. A total of 148 (15.5%) patients developed major adverse cardiovascular events (MACEs). Both SI (HR 1.52, 95% CI 1.06-2.19, P = 0.02) and elevated hs-cTnI (HR 3.18, 95% CI 2.07-4.89, P < 0.01) were independent predictors of a MACE in patients with stable CAD. When stratified by hs-cTnI level, SI independently predicted MACE-free survival only in those with elevated hs-cTnI (HR 1.51, 95% CI 1.01-2.24, P = 0.04). CONCLUSIONS: SI independently predicted MACE in patients with stable CAD and high hs-cTnI, but not in those with low hs-cTnI. Hs-cTnI may be used to stratify stable CAD patients who have SI for intensive lipid-lowering therapy using non-statin agents.

Characteristics, Mechanism and Long-Term Ablation Outcome of Atrial Tachycardias After Mitral Valvular Surgery and Concomitant Cox-MAZE IV Procedure.

The incidence of atrial tachycardia (AT) after rheumatic mitral valvular (RMV) surgery has been well described. However, there have been few reports on the characteristics, mechanism, and long-term ablation outcome of ATs after RMV surgery and concomitant Cox-MAZE IV procedure.The present study reviewed consecutive patients who underwent AT ablation between May 2008 and July 2013. All patients were refractory to antiarrhythmic drugs (AADs) and had a history of RMV surgery and Cox-MAZE IV procedure. A total of 34 patients underwent AT ablation after RMV surgery and concomitant Cox-MAZE IV procedure, and presented 57 mappable and 2 unmappable ATs. The 57 mappable ATs included 14 focal-ATs and 43 reentry-ATs. Ten of the 14 focal-like ATs were located at the pulmonary vein (PV) antrum and border of a box lesion. Of the 43 reentry-ATs, 16 were marco-reentrant around the mitral annulus (MA) and 16 around the tricuspid annulus. There were 41 atypical ATs (non-cavotricuspid isthmus related) including 16 ATs related to the box lesion and 21 ATs related to other Cox-MAZE IV lesions. The AT were successfully terminated in 33 (97.1%) patients. After mean follow-up of 46.9 ± 15.7 months, 25 (73.5%) patients maintained sinus rhythm without AADs after a single procedure and 28 (82.4%) patients after repeated procedures.The recurrent ATs after RMV surgery and concomitant Cox-MAZE IV were mainly reentry mechanism, and largely related to LA. An incomplete lesion or re-conductive gaps in a prior lesion might be the predominant mechanisms for these ATs. Catheter-based mapping and ablation of these ATs seems to be effective and safe during a long-term follow-up.

Genetically deprived vitamin D exposure predisposes to atrial fibrillation.

AIMS: Low vitamin D level is associated with atrial fibrillation (AF) and may be implicated in its pathogenesis. METHODS AND RESULTS: We studied single nucleotide polymorphisms (SNPs) of vitamin D mechanistic pathways and serum 25-hydroxyvitamin D [25(OH)D] levels in an age- and gender-matched case-control study (controls without AF: mean age 68.6 ± 8.7 years, female 25%; n = 1019; with AF: mean age 69.7 ± 9.5 years, female 30%; n = 156) recruited from a Chinese clinical cohort of patients with stable coronary artery disease. Twelve SNPs involved in the vitamin D mechanistic pathways were studied [biosynthetic: rs4646536, rs10877012, rs3829251, rs1790349; activation: rs2060793, rs1993116; vitamin D-binding protein (VBP)/group-specific component (GC): rs4588, rs7041, rs2282679, rs1155563; and vitamin D receptor: rs1544410, rs10735810]. A genetic risk score (GRS) (0-8) was constructed from SNPs associated with serum 25(OH)D as a proxy to lifelong vitamin D-deficient state. All 4 SNPs involved in the VBP/GC were significantly associated with serum 25(OH)D (rs4588, P < 0.001; rs2282679, P < 0.001; rs7041, P = 0.011; rs1155563, P < 0.001; all other SNPs, P > 0.05). Vitamin D GRS (points 0-8) generated from these 4 SNPs was independently predictive of serum 25(OH)D [B = 0.54, 95% confidence interval (CI) 0.30-0.79; P < 0.001]. Genetically deprived vitamin D status as denoted by a low GRS (0-3) independently predicted an increased risk of AF, compared to a high GRS (4-8) (odds ratio = 1.848, 95% CI 1.217-2.805; P = 0.004). CONCLUSION: Genetically deprived vitamin D exposure predisposes to increased AF among patients with coronary artery disease. Whether VBP/GC may alter the risk of AF via alternative mechanisms warrants further studies.

PR interval prolongation in coronary patients or risk equivalent: excess risk of ischemic stroke and vascular pathophysiological insights.

BACKGROUND: Whether PR prolongation independently predicts new-onset ischemic events of myocardial infarction and stroke was unclear. Underlying pathophysiological mechanisms of PR prolongation leading to adverse cardiovascular events were poorly understood. We investigated the role of PR prolongation in pathophysiologically-related adverse cardiovascular events and underlying mechanisms. METHODS: We prospectively investigated 597 high-risk cardiovascular outpatients (mean age 66 ± 11 yrs.; male 67%; coronary disease 55%, stroke 22%, diabetes 52%) for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and cardiovascular death. Vascular phenotype was determined by carotid intima-media thickness (IMT). RESULTS: PR prolongation >200 ms was present in 79 patients (13%) at baseline. PR prolongation >200 ms was associated with significantly higher mean carotid IMT (1.05 ± 0.37 mm vs 0.94 ± 0.28 mm, P = 0.010). After mean study period of 63 ± 11 months, increased PR interval significantly predicted new-onset ischemic stroke (P = 0.006), CHF (P = 0.040), cardiovascular death (P < 0.001), and combined cardiovascular endpoints (P < 0.001) at cut-off >200 ms. Using multivariable Cox regression, PR prolongation >200 ms independently predicted new-onset ischemic stroke (HR 8.6, 95% CI: 1.9-37.8, P = 0.005), cardiovascular death (HR 14.1, 95% CI: 3.8-51.4, P < 0.001) and combined cardiovascular endpoints (HR 2.4, 95% CI: 1.30-4.43, P = 0.005). PR interval predicts new-onset MI at the exploratory cut-off >162 ms (C-statistic 0.70, P = 0.001; HR: 8.0, 95% CI: 1.65-38.85, P = 0.010). CONCLUSIONS: PR prolongation strongly predicts new-onset ischemic stroke, MI, cardiovascular death, and combined cardiovascular endpoint including CHF in coronary patients or risk equivalent. Adverse vascular function may implicate an intermediate pathophysiological phenotype or mediating mechanism.

Clinical Characteristics, Management, and Outcomes of Hospitalized Heart Failure in a Chinese Population-The Hong Kong Heart Failure Registry.

BACKGROUND: Epidemiological data for heart failure (HF) in the Chinese population is scarce. In this study, we described the clinical characteristics and outcomes of new-onset HF in our population. METHODS AND RESULTS: We conducted a retrospective, observational study on consecutive Chinese patients hospitalized for new-onset HF between 2005 and 2012 in our center. A total of 1940 patients (mean age, 78.2 ± 11.8 years, 54.2% female) were identified. The rate of new HF hospitalization was 0.59 per 1000 population. The most prevalent comorbidities were hypertension (69.8%) and coronary artery disease (29.3%), and 52.3% had HF with preserved ejection fraction (HFpEF). The all-cause mortality was 19.5% at 1 year, 32.1% at 2 years, and 54% at 5 years. Cardiovascular mortality was 7.2% at 1 year, 11.8% at 2 years, and 20.7% at 5 years. No difference in all-cause mortality or cardiovascular mortality was observed between those with HF with reduced ejection fraction than HFpEF. CONCLUSIONS: Our patients with new-onset HF shared similar clinical characteristics with the Caucasian population. The prognosis was poor with high all-cause mortality for both HFpEF and HF with reduced ejection fraction.

Ischemic stroke and intracranial hemorrhage with aspirin, dabigatran, and warfarin: impact of quality of anticoagulation control.

BACKGROUND AND PURPOSE: Little is known about the impact of quality of anticoagulation control, as reflected by time in therapeutic range (TTR), on the effectiveness and safety of warfarin therapy in Chinese patients with atrial fibrillation. We investigated the risks of ischemic stroke and intracranial hemorrhage (ICH) in relation to warfarin at various TTRs in a real-world cohort of Chinese patients with atrial fibrillation receiving warfarin and compared with those on dabigatran, aspirin, and no therapy. METHODS: This is an observational study. RESULTS: Of 8754 Chinese patients with atrial fibrillation and CHA2DS2-VASc ≥1 (79.5±9.2 years; CHA2DS2-VASc, 4.1±1.5; and Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly (>65 years), Drugs/Alcohol Concomitantly [HAS-BLED], 2.2±0.9), 16.3% received warfarin, 41.1% aspirin, 4.5% dabigatran, and 38.1% received no therapy. The incidence of ischemic stroke was highest in patients with no therapy (10.38%/y), followed by patients on aspirin (7.95%/y). The incidence of stroke decreased progressively with increasing TTR quartiles (<17.9%, 17.9%-38.8%, 38.8%-56.2%, and >56.2%) from 7.34%/y (first quartile) to 3.10%/y (fourth quartile). Patients on dabigatran had the lowest incidence of stroke among all groups (2.24%/y). The incidence of ICH was lowest in patients on dabigatran (0.32%/y) compared with those on warfarin (0.90%/y), aspirin (0.80%/y), and no therapy (0.53%/y). ICH incidence decreased with increasing TTR from 1.37%/y (first quartile) to 0.74%/y (fourth quartile). CONCLUSIONS: In Chinese patients with atrial fibrillation, the benefits of warfarin therapy for stroke prevention and ICH risk are closely dependent on the quality of anticoagulation, as reflected by TTR. Even at the top TTR quartile, warfarin was associated with a higher stroke and ICH risk than dabigatran.

Electrophysiologic characteristics of ventricular arrhythmias arising from the aortic mitral continuity-potential role of the conduction system.

INTRODUCTION: Catheter ablation of ventricular arrhythmia (VA) at the fibrous aortic mitral continuity (AMC) has been described, yet the nature of the arrhythmogenic substrate remains unknown. METHODS: Procedural records of 528 consecutive patients undergoing ablation of VA at Mayo Clinic, Rochester, MN, were reviewed. The electrocardiographic and electrophysiologic characteristics of patients with successful ablation at the AMC were analyzed to characterize the underlying arrhythmogenic substrate. RESULTS: Of the 21 patients (mean age 53.2 ± 13.4 years, 47.6% male) who underwent ablation of VA at the AMC with acute success, prepotentials (PPs) were found at the ablation sites preceding the ventricular electrogram (VEGM) during arrhythmias in 13 (61.9%) patients and during sinus rhythm in 7 (53.8%) patients. VAs with PPs were associated with a significantly higher burden of premature ventricular complexes (PVCs; 26.1 ± 10.9% vs. 14.9 ± 10.1%, P = 0.03), shorter VEGM to QRS intervals (9.0 ± 28.5 milliseconds vs. 33.1 ± 8.8 milliseconds, P = 0.03), lower pace map scores (8.7 ± 1.6 vs. 11.4 ± 0.8, P = 0.001), and a trend toward shorter V-H intervals during VA (32.1 ± 38.6 milliseconds vs. 76.3 ± 11.1 milliseconds, P = 0.06) as compared to those without PP. A strong and positive correlation was found between V-H interval and QRS duration during arrhythmia in those with PPs (B = 2.11, R(2) = 0.97, t = 13.7, P < 0.001) but not in those without PPs. CONCLUSION: Local EGM characteristics and relative activation time of the His bundle suggest the possibility of conduction tissue as the origin for VA arising from the fibrous AMC. Specific identification and targeting of PPs when ablating VAs at this location may improve procedural success.

First clinical experience of the safety and feasibility of total subcutaneous implantable defibrillator in an Asian population.

AIMS: The safety and feasibility of a subcutaneous implantable cardioverter-defibrillator (S-ICD) has been demonstrated in the treatment of life-threatening ventricular tachyarrhythmias (VT). Nonetheless, its safety and feasibility in an Asian population with smaller body-build is unclear. METHODS AND RESULTS: Twenty-one Asian patients who underwent S-ICD from 1 April 2014 to 2 February 2015 in five institutions in Hong Kong and Singapore were retrospectively reviewed. Twenty-one patients with a mean age of 50.0 ± 14.1 years (range 29-77 years, 82.6% male) were included. Among them, 17 (81.0%) were Chinese, 3 (14.3%) were Malay, and 1 (4.8%) was Indian. Their mean body mass index was 23.0 ± 4.0 kg/m(2). An S-ICD was implanted for primary and secondary prevention in 13 (61.9%) and 8 (38.1%) patients, respectively. The indications included Brugada syndrome (n = 6, 28.6%), ischaemic cardiomyopathy (CMP, n = 6, 28.6%), dilated CMP (n = 4, 19.0%), hypertrophic CMP (n = 2, 9.5%), and idiopathic ventricular fibrillation (n = 2, 9.5%). Three patients (14.3%) had prior infected transvenous ICD. There were no acute complications but eight wound complications (persistent wound bleeding requiring intervention = 2; delayed wound healing: upper sternal wound = 3; generator site = 1; local wound infection = 2) were observed in six (28.2%) patients. After a mean follow-up of 107.2 ± 81.3 days (range of 14-254 days), one patient underwent three successful appropriate shocks for treatment of VTs. No inappropriate therapy was documented. CONCLUSION: Our initial experience shows that S-ICD is a feasible treatment for VT among an Asian population with smaller body-build. There was nonetheless a relatively high rate of wound complications.

Endocavitary structures in the outflow tract: anatomy and electrophysiology of the conus papillary muscles.

Catheter ablation is an increasingly used and successful treatment choice for right ventricular outflow tract (RVOT) arrhythmias. While the role of endocavitary structures and the regional morphology of the ventricular inflow tract and the right atrium as a cause for difficulty with successful ablation are well described, similar issues within the RVOT are not well understood. It is also not commonly appreciated that one of the papillary muscles is located within the proximal RVOT. We report 3 patients in which ventricular arrhythmia was targeted and ablated in the conus papillary muscle. The anatomic features, potential role of the fascicular conduction system, and unique challenges with mapping arrhythmia arising from this structure are discussed.

Distinguishing ventricular arrhythmia originating from the right coronary cusp, peripulmonic valve area, and the right ventricular outflow tract: utility of lead I.

INTRODUCTION: Outflow tract ventricular arrhythmia (OTVA) can be complicated to target for ablation when originating from either the periaortic or pulmonary valve (PV) region. Both sites may present with a small R wave in lead V1. However, the utility of lead I in distinguishing these arrhythmia locations is unknown. METHODS AND RESULTS: Thirty-six consecutive patients (mean age 41 ± 14 years, 13 male) underwent catheter ablation for OTVA. OTVA origin was determined from intracardiac electrogram tracings and electroanatomic maps. Observers blinded to results measured QRS waveform amplitude and duration from standard 12-lead ECG tracings. Measurements with highest diagnostic performance were modeled into an algorithm. Sites of successful ablation were anterior right ventricular outflow tract (RVOT; n = 6), posterior RVOT (n = 4), PV (n = 18), and right coronary cusp (RCC; n = 8). Highest performing surface ECG discriminators were from lead I to V1 vectors: RCC, lead I R wave ≥ 1.5 mV, and V1 R wave ≥2.0 mV (sensitivity 87%, specificity 93%); PV, V1 R wave > 0 mV, and lead I R/(R+S) ≤ 0.75 (sensitivity 78%, specificity 72%); anterior RVOT, V1 R wave = 0 mV, and lead I R/(R+S) <0.4 (sensitivity 67%, specificity 97%); posterior RVOT, V1 R wave > 0 mV, and lead I R/(R+S) > 0.75 (sensitivity 75%, specificity 84%). Sequential algorithmic application of these criteria resulted in an overall accuracy of 72% in predicting site of OTVA origin. CONCLUSIONS: A relatively large R wave in lead I is seen with RCC origin but not PV origin. A sequential algorithm has limited but potentially significant value beyond assessment of lead I in approaching OTVA.

The anatomic basis for ventricular arrhythmia in the normal heart: what the student of anatomy needs to know.

The traditional route for teaching cardiac anatomy involves didactic instruction, cadaver dissections, and familiarization with the main structure and relationships of the cardiac chambers, valves, and vasculature. In contemporary cardiac electrophysiology, however, a very different view of anatomy is required including details rarely appreciated with a general overview. In this review, we discuss the critical advances in cardiac electrophysiology that were possible only because of understanding detailed anatomic relationships. While we briefly discuss the clinical relevance, we explain in depth the necessary structural information for the student of clinical anatomy. Interspersed through the text are boxes that highlight and summarize the critical pieces of knowledge to be borne in mind while studying the fascinating structural anatomy of the human heart.

The CEPHEUS Pan-Asian survey: high low-density lipoprotein cholesterol goal attainment rate among hypercholesterolaemic patients undergoing lipid-lowering treatment in a Hong Kong regional centre.

OBJECTIVES. To evaluate attainment of low-density lipoprotein cholesterol goals among hypercholesterolaemic patients undergoing lipid-lowering drug treatment in Hong Kong and to identify potential determinants of treatment outcomes. DESIGN. Cross-sectional observational study. SETTING. A single site in Hong Kong, as part of the CEPHEUS Pan-Asian survey. PATIENTS. Subjects with hypercholesterolaemia aged 18 years or above, who had been on lipid-lowering drug treatment for at least 3 months with no dose adjustment for at least 6 weeks. RESULTS. A total of 561 such patients (mean age, 65.3; standard deviation, 9.7 years) were evaluated. Most had major cardiovascular risk factors; 534 (95.2%) of 561 patients had coronary heart disease and 534 (95.4%) of 560 patients had low-density lipoprotein cholesterol goals set at lower than 70 mg/dL. In all, 465 (82.9%) patients attained their respective low-density lipoprotein cholesterol goals. Among 75 patients who had coronary heart disease or equivalent risk, and multiple risk factors with a 10-year coronary heart disease risk of over 20%, 62 (82.7%) attained their respective low-density lipoprotein cholesterol goals. Significant predictors of low-density lipoprotein cholesterol goal attainment included the patient's baseline lipid profile (total cholesterol and low-density lipoprotein cholesterol levels), blood pressure, and drugs (statin/non-statin) used for treatment. CONCLUSIONS. Hypercholesterolaemic patients undergoing lipid-lowering drug treatment in the present Hong Kong study were able to achieve a very high attainment rate for the low-density lipoprotein cholesterol goal, despite the fact that most of them had major cardiovascular risk factors.

Mendelian randomization analysis of vitamin D in the secondary prevention of hypertensive-diabetic subjects: role of facilitating blood pressure control.

BACKGROUND: Vitamin D (Vit-D) promotes vascular repair and its deficiency is closely linked to the development of type 2 diabetes mellitus (T2DM) and hypertension. Whether genetially predicted vitamin D status (serological 25-hydroxyvitamin D [25(OH)D]) confers secondary protection against cardiovascular diseases (CVD) among high-risk hypertensive-diabetic subjects was unknown. METHODS: This is a prospective, individual-data, two-sample Mendelian randomization study. We interrogated 12 prior GWAS-detected SNPs of comprehensive Vit-D mechanistic pathways using high-throughput exome chip analyses in a derivation subcohort (n = 1460) and constructed a genetic risk score (GRS) (rs2060793, rs4588, rs7041; F-statistic = 32, P < 0.001) for causal inference of comprehensive CVD hard clinical endpoints in an independent sample of hypertensive subjects (n = 3746) with prevailing co-morbid T2DM (79%) and serological 25(OH)D deficiency [< 20 ng/mL] 45%. RESULTS: After 55.6 ± 28.9 months, 561 (15%) combined CVD events including myocardial infarction, unstable angina, ischemic stroke, congestive heart failure, peripheral vascular disease, and cardiovascular death had occurred. Kaplan-Meier analysis showed that genetically predicted reduced vitamin D status was associated with reduced event-free survival from combined CVD events (log-rank = 13.5, P = 0.001). Multivariate-adjusted per-allele increase in GRS predicted reduced combined CVD events (HR = 0.90 [0.84 to 0.96], P = 0.002). Mendelian randomization indicates that increased Vit-D exposure, leveraged through each 1 ng/mL genetically instrumented rise of serum Vit-D, protects against combined CVD events (Wald's estimate: OR = 0.86 [95%CI 0.75 to 0.95]), and myocardial infarction (OR = 0.76 [95%CI 0.60 to 0.90]). Furthermore, genetically predicted increase in Vit-D status ameliorates risk of deviation from achieving guideline-directed hypertension control (JNC-8: systolic target < 150 mmHg) (OR = 0.89 [95%CI 0.80 to 0.96]). CONCLUSIONS: Genetically predicted increase in Vit-D status [25(OH)D] may confer secondary protection against incident combined CVD events and myocardial infarction in a hypertensive-diabetic population where serological 25(OH)D deficiency is common, through facilitating blood pressure control.

Protocol for Home-Based Solution for Remote Atrial Fibrillation Screening to Prevent Recurrence Stroke (HUA-TUO AF Trial): a randomised controlled trial.

INTRODUCTION: Current international guidelines recommend ECG monitoring after an ischaemic stroke to detect atrial fibrillation (AF) in order to prevent stroke recurrence. However, optimal strategies to detect AF and the downstream management to prevent stroke recurrence remain to be established. The objective of the study was to explore the use of long-term home-based ECG monitoring for AF detection and stroke prevention in patients with a history of stroke. METHODS AND ANALYSIS: This prospective, randomised, open-label trial with blinded endpoint adjudication aimed to evaluate the efficacy of long-term home-based ECG monitoring for AF detection and stroke prevention in a 24-month period. Patients aged >18 years with a history of ischaemic stroke will be stratified according to the time from the index ischaemic stroke: <1, 1-3 and >3 years and then randomised in 1:1 to (1) home-based AF screening and (2) control. The home-based AF screening system comprises (1) a handheld single-lead ECG recorder (Comfit Healthcare Devices, Hong Kong SAR, China) and (2) a patient-facing smartphone application specially designed for the study. Patients randomised to the home-based AF group will record a 30 s single-lead ECG using a specially designed handheld ECG device every morning or when symptomatic. All remotely obtained data will be automatically transmitted in real-time through the study smartphone application to a secured cloud hosting and analysed using an artificial intelligence-based diagnostic system. When a diagnosis of AF is made with the system, the patients will be called back for a formal cardiology consultation within 1 week. The primary endpoint is the time to first detection of AF at 24 months of follow-up. Secondary endpoints include recurrent stroke or transient ischaemic attack, initiation of long-term anticoagulation therapy, hospitalisation for heart failure, cardiovascular death and all-cause death. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of The University of Hong Kong, and Hong Kong West Cluster, Hospital Authority, Hong Kong SAR, China. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04523649.