Are cardiovascular risk factors also associated with the incidence of atrial fibrillation? A systematic review and field synopsis of 23 factors in 32 population-based cohorts of 20 million participants

Abstract

Established primary prevention strategies of cardiovascular diseases are based on understanding of risk factors, but whether the same risk factors are associated with atrial fibrillation (AF) remains unclear. We conducted a systematic review and field synopsis of the associations of 23 cardiovascular risk factors and incident AF, which included 84 reports based on 28 consented and four electronic health record cohorts of 20,420,175 participants and 576,602 AF events. We identified 3-19 reports per risk factor and heterogeneity in AF definition, quality of reporting, and adjustment. We extracted relative risks (RR) and 95 % confidence intervals [CI] and visualised the number of reports with inverse (RR [CI]<1.00), or direct (RR [CI]>1.00) associations. For hypertension (13/17 reports) and obesity (19/19 reports), there were direct associations with incident AF, as there are for coronary heart disease (CHD). There were inverse associations for non-White ethnicity (5/5 reports, with RR from 0.35 to 0.84 [0.82-0.85]), total cholesterol (4/13 reports from 0.76 [0.59-0.98] to 0.94 [0.90-0.97]; 8/13 reports with non-significant inverse associations), and diastolic blood pressure (2/11 reports from 0.87 [0.78-0.96] to 0.92 [0.85-0.99]; 5/11 reports with non-significant inverse associations), and direct associations for taller height (7/10 reports from 1.03 [1.02-1.05] to 1.92 [1.38-2.67]), which are in the opposite direction of known associations with CHD. A systematic evaluation of the available evidence suggests similarities as well as important differences in the risk factors for incidence of AF as compared with other cardiovascular diseases, which has implications for the primary prevention strategies for atrial fibrillation.

Keywords: Atrial fibrillation; cardiovascular disease; clinical guidelines; primary prevention; risk factors.

Figure 1:

Associations of 23 risk factors and incidence of atrial fibrillation according to number of reports, number of events, and direction of association. AF – atrial fibrillation, BP – blood pressure, EHR – electronic health record, HDL – high-density lipoprotein, LDL – low-density lipoprotein, sig. – significant. Risk factor and reference group definitions are detailed in individual risk factors plots (Figures 2–6 and Suppl. Figures S2–S19 in Appendix, available online at www.thrombosis-online.com). Each dot represents one report, colour–coded to indicate the direction of association, and in order of most extreme inverse to most extreme direct point estimate. Dots are scaled by the number of AF events (<100, 100–<1000, 1000–<10000, 10000–<100000, or ≥100000). References correspond to each dot from left to right sequence. Associations are classified as inverse (relative risk (RR) <1.00), null or mixed (RR=1.00 or show opposite associations among subpopulations), or direct (RR>1.00). Association were regarded as significant if the 95 % CI did not cross unity.

Figure 2:

Association of ethnicity and incidence of AF: 5 reports from 1 country with 386,115 events. EHR – electronic health record, age range in years, follow-up in years (mean, median, or maximum), AF – atrial fibrillation, CI – confidence interval, N/23 – number (of factors) out of 23, CVD – cardiovascular disease, SD – standard deviation, NR – not reported, USA – United States of America, • – yes, ○ – no, -- – not applicable. Risk factor adjustment refers to whether adjustment was made for the 23 risk factors under review, 6 CVD risk factors, and prevalent and incident CVD events. Example: ARIC adjusted for 5/23 risk factors, age, sex, blood pressure (i. e. any of systolic blood pressure, diastolic blood pressure, hypertension, or blood pressure lowering medication), and diabetes mellitus, but not smoking or lipids (i. e. any of total cholesterol, low–density lipoprotein cholesterol, high–density lipoprotein cholesterol, triglycerides, hyperlipidaemia, or lipid lowering medication), and prevalent, but not incident CVD events. For cohort abbreviations see Table 2 (available online at www.thrombosis-online.com).

Figure 3:

Association of alcohol intake and incidence of AF: 10 reports from 5 countries with 18,997 events. Legend see Figure 2 abbreviations, and g – grams, (w) – women, (m) – men.

Figure 4:

Association of diastolic blood pressure and incidence of AF: 11 reports from 7 countries with 4796 events. See Figure 2 abbreviations, and mmHg – millimetres of mercury. Risk factor adjustment for BP in this instance refers to whether systolic blood pressure, hypertension, or blood pressure lowering medication were adjusted for.

Figure 5:

Association of total cholesterol and incidence of AF: 13 reports from 8 countries with 7129 events. See Figure 2 abbreviations, and mg/dl – milligrams per decilitre, mmol/l – millimoles per litre. Risk factor adjustment for lipids in this instance refers to whether low–density lipoprocholesterol, high–density lipoprotein cholesterol, triglycerides, hyperlipidaemia, or lipid lowering medication were adjusted for. Total cholesterol reported as mmol/l for CHS, GPPS, TS and BHS was converted to mg/dl using the conversion 1 mmol/l = 38.66976 mg/dl.

Figure 6:

Association of height and incidence of AF: 10 reports from 6 countries with 7181 events. See Figure 2 abbreviations, and cm – centimetres, (m) – men, (w) – women.