Association of premature ventricular complexes and risk of ischemic stroke: A systematic review and meta-analysis
Authors: Rujirachun P , Wattanachayakul P , Phichitnitikorn P , Charoenngam N , Kewcharoen J , Winijkul A 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.
Background/objectives: Recent studies have suggested that patients with premature ventricular complexes (PVCs) may have a higher risk of ischemic stroke. However, the data are limited and inconclusive. We conducted a systematic review and meta-analysis to investigate the association between PVCs and the risk of ischemic stroke.

Methods
A comprehensive literature review was conducted by searching for published articles indexed in MEDLINE and EMBASE databases from inception through September 25, 2020, to identify studies that compared the risk of ischemic stroke between patients with PVCs and individuals without PVCs. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of Dersimonian and Laird.

Results
A total of four observational studies (2 prospective and 2 retrospective cohort studies) with 42,677 participants met the eligibility criteria and were included in the meta-analysis. We found that patients with PVCs have a significantly higher risk of ischemic stroke than individuals without PVCs with the pooled RR of 1.31 (95% CI, 1.07-1.60, I2 = 43%). Conclusions: From our systematic review and meta-analysis, we found that PVCs are associated with a higher risk of ischemic stroke. Whether this association is causal and how it should be addressed in clinical practice require further investigations. Table 1Ofoma et al.Agarwal et al.Lin et al.Im et al.Year of publication2012201520152018Country of originUnited StatesUnited StatesTaiwanKoreaStudy designProspective cohort studyProspective cohort studyRetrospective cohort studyRetrospective cohort studyStudy subjectsCases: Cases were patients with PVCs who were diagnosed based on 2-minute ECG. Cases were identified from the 1987 to 1989 ARIC study. Comparators: Comparators were the rest of the patients in the study who did not carry a diagnosis of PVCs. The average follow-up time was 13 years. Patients with a history of stroke, CAD, SAH, and ICH were excluded from the analysis.Cases: Cases were patients with PVCs who were diagnosed based on routine ECG. Cases were identified from the 2003 to 2007 REGARDS study. Comparators: Comparators were the rest of the patients in the study who did not carry a diagnosis of PVCs. An average (SD) follow-up time was 6 (2) years. Patients with a history of stroke or TIA and hemorrhagic stroke were excluded from the analysis.Cases: Cases were patients with PVCs (&lt;720 beats/day) who were diagnosed based on 24-hour ECG monitoring. Cases were identified from the 2002 to 2004 Taipei Veterans General Hospital database. Comparators: Comparators were the rest of the patients in the database who did not carry a diagnosis of PVCs. The average follow-up time was 10 ± 1 years. Patients with a history of sustained or non-sustained VT, PPM, HF, MI, ablation, VHD, and PVCs &gt; 720 beats/day were excluded from the analysis.Cases: Cases were patients with PVCs (&gt;10%) who were diagnosed based on standard ECG or 24-hour ECG monitoring. Cases were identified from the 2013 to 2015 Kosin University database. Comparators: Comparators were the rest of the patients in the database who did not carry a diagnosis of PVCs. The average follow-up time was 4 years. Patients with a history of cardiomyopathy, VHD, CHD, hepatic or renal disease, and acute cardiovascular or cerebrovascular event within 3 months, any trauma or surgery within 3 months, hyperthyroidism, uncontrolled HT, malignancy, CTD, IHD, and any acute or chronic inflammatory disease were excluded from the analysis.Number of subjectsCases: 793Comparators: 13,700Cases: 1,415Comparators: 23,045Cases: 1,074 (Uniform PVCs), 1,166 (Multiform PVCs)Comparators: 1,111Cases: 203Comparators: 170Baseline characteristics of subjectsMean age, year: Cases: 55.97Comparators: 53.85 Mean BMI, kg/m2:Cases: 28.47Comparators: 27.61 Mean TC, mg/dL: Cases: 211.85Comparators: 214.69 Female: Case: 50.82%Comparators: 57.06% White: Case: 68.1%Comparators: 73.38% HT:Cases: 44.54 %Comparators: 32.80 % Diabetes:Cases: 13.98%Comparators: 10.76% Smoking:Cases: 25.73%Comparators: 25.83% Mean age, year: Cases: 68.3 ± 9.2 Comparators: 64.3 ± 9.3 Mean BMI, kg/m2:Cases: 29.2 ± 6.1Comparators: 29.3 ± 6.2 Mean SBP, mmHg:Cases: 130.1 ± 16.9 Comparators: 126.9 ± 16.4 Female:Cases: 45.4%Comparators: 59% Black: Cases: 41.9%Comparators: 39.9% EducationNo high school:Cases: 15.5%Comparators: 11.1% High school/no college:Cases: 26.3%Comparators: 25.6% College or professional: Cases: 58.2%Comparators: 63.3% Geographic regionNon-Belt:Cases: 47.2%Comparators: 43.9% Belt:Cases: 33.9%Comparators: 34.8% Buckle:Cases: 19.0%Comparators: 21.3% Previous heart disease: Cases: 25.4%Comparators: 12.2% HT:Cases: 64.7%Comparators: 56.2% DM: Cases: 21.8%Comparators: 19.1% AF: Cases: 9.7%Comparators: 7.8% LVH: Cases: 11.2%Comparators: 9.4% Current smoking:Cases: 13.0%Comparators: 14.0% Use of warfarin: Case: 3.5%Comparators: 2.7% Use of aspirin: Case: 48.1%Comparators: 40.9%Mean age, year: Cases: 58.7 ± 19.3 (Uniform PVCs), 65.7 ± 16.9 (Multiform PVCs)Comparators: 50.7 ± 20.1 Female:Cases: 44.9% (Uniform PVCs), 31.4% (Multiform PVCs)Comparators: 53.4% DM: Cases: 7.4% (Uniform PVCs), 9.4% (Multiform PVCs)Comparators: 5.6% HT: Cases: 31.2% (Uniform PVCs), 38.0% (Multiform PVCs)Comparators: 21.6% Hyperlipidemia: Cases: 7.4% (Uniform PVCs), 5.8% (Multiform PVCs)Comparators: 5.5% CKD: Cases: 1.4% (Uniform PVCs), 1.4% (Multiform PVCs)Comparators: 0.3% Cirrhosis: Cases: 0.8% (Uniform PVCs),0.8% (Multiform PVCs)Comparators: 0.5% AF: Cases: 6.7 % (Uniform PVCs), 6.8 % (Multiform PVCs)Comparators: 6.7% CLD: Cases: 2.6% (Uniform PVCs), 2.8% (Multiform PVCs)Comparators: 2.0% Use of AAD: Cases: 0.2% (Uniform PVCs), 0.5% (Multiform PVCs)Comparators: 0.5% Use of anti-HT: Cases: 16.4% (Uniform PVCs), 20.8 % (Multiform PVCs)Comparators: 12.2% Use of statin: Cases: 7.2 % (Uniform PVCs), 5.7% (Multiform PVCs)Comparators: 5.1% Mean age, year:Cases: 61.0 ± 15.2Comparators: 57.6 ± 16.4 Female: Cases: 56.7 %Comparators: 52.7% DM:Cases: 17.5 %Comparators: 20.0% HT:Cases: 28.4%Comparators: 30.6% CAD: Cases: 11.3%Comparators: 12.4% MedicationAmiodarone: Cases: 7.7%Comparators: 0% Propafenone: Cases: 1.0%Comparators: 0% Digoxin: Cases: 5.2%Comparators: 4.8% Beta-blocker:Cases: 53.6%Comparators: 8.2% CCB: Cases: 21.6%Comparators: 20% ARB & ACEI: Cases: 17.0%Comparators: 16.4% Statin: Cases: 39.4%Comparators: 37.6% Aspirin: Cases: 24.6%Comparators: 25.3% Clopidogrel: Cases: 13.4%Comparators: 12.0% VKA: Cases: 9.8%Comparators: 11.2%Diagnosis of PVCsPVCs were detected by 2-minute ECG.PVCs were detected by routine ECG. PVCs were detected by 24-hour Holter monitoring.PVCs were detected by standard ECG or 24-hour Holter monitoring.Diagnosis of strokeThe diagnosis of ischemic stroke was supported by annual telephone follow-up and a community surveillance system. Stroke was diagnosed by agreement of computer and reviewer classification. Disagreements were adjudicated by a second physician-reviewer.The diagnosis of ischemic stroke was supported by telephone follow-up every 6 months. Stroke events were defined following the WHO definition. The stroke was diagnosed and confirmed by an adjudication committee.Ischemic stroke was diagnosed by physicians and also confirmed by brain imaging.Ischemic stroke was determined by a neurologist if the patient felt painless, weakness, sudden numbness or dead feeling on one side of the body, sudden painless loss of vision, and sudden loss of ability to understand what people were saying and also confirmed by brain MRI in all patients.Confounder adjusted in the multivariate analysisAge, race, gender, BMI, HT, diabetes, smoking, TC levelsAge, sex, race, geographic region, education level, previous heart disease, SBP, use of antihypertensive medication, LVH, AF, DM, current smoking, use of warfarin and aspirinAge, sex, HT, DM, CKD, use of hypertensive medicationAge, AF, HT, LVH, E/E’, MR grade, NT-proBNPNewcastle-Ottawa scoreSelection: 4 stars Comparability: 2 stars Outcome: 3 starsSelection: 4 stars Comparability: 2 stars Outcome: 3 starsSelection: 3 stars Comparability: 1 star Outcome: 3 starsSelection: 4 stars Comparability: 2 stars Outcome: 3 starsBaseline characteristics of studies included in the meta-analysisAbstract Figure. Forest plot of the meta-analysis