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Cardiovascular Health and Atrial Fibrillation or Flutter: A Cross-Sectional Study from ELSA-Brasil

Abstract

Background

The association between ideal cardiovascular health (ICVH) status and atrial fibrillation or flutter (AFF) diagnosis has been less studied compared to other cardiovascular diseases.

Objective

To analyze the association between AFF diagnosis and ICVH metrics and scores in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Methods

This study analyzed data from 13,141 participants with complete data. Electrocardiographic tracings were coded according to the Minnesota Coding System, in a centralized reading center. ICVH metrics (diet, physical activity, body mass index, smoking, blood pressure, fasting plasma glucose, and total cholesterol) and scores were calculated as proposed by the American Heart Association. Crude and adjusted binary logistic regression models were built to analyze the association of ICVH metrics and scores with AFF diagnosis. Significance level was set at 0.05.

Results

The sample had a median age of 55 years and 54.4% were women. In adjusted models, ICVH scores were not significantly associated with prevalent AFF diagnosis (odds ratio [OR]:0.96; 95% confidence interval [95% CI]:0.80-1.16; p=0.70). Ideal blood pressure (OR:0.33; 95% CI:0.15–0.74; p=0.007) and total cholesterol (OR:1.88; 95% CI:1.19–2.98; p=0.007) profiles were significantly associated with AFF diagnosis.

Conclusions

No significant associations were identified between global ICVH scores and AFF diagnosis after multivariable adjustment in our analyses, at least partially due to the antagonistic associations of AFF with blood pressure and total cholesterol ICVH metrics. Our results suggest that estimating the prevention of AFF burden using global ICVH scores may not be adequate, and ICVH metrics should be considered in separate.

Atrial Fibrillation; Atrial Flutter; Epidemiology; Stroke

Resumo

Fundamento

A associação entre o status de saúde cardiovascular ideal ( ideal cardiovascular health ( ICVH) e diagnóstico de fibrilação ou flutter atrial (FFA) foi menos estudado em comparação a outras doenças cardiovasculares.

Objetivos

Analisar a associação entre o diagnóstico de FFA e métricas e escores de ICVH no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil).

Métodos

Este estudo analisou dados de 13141 participantes com dados completos. Os traçados eletrocardiográficos foram codificados de acordo com o Sistema de Minnesota, em um centro de leitura centralizado. As métricas do ICVH (dieta, atividade física, índice de massa corporal, tabagismo, glicemia de jeju, e colesterol total) e escores do ICVH foram calculados conforme proposto pela American Heart Association . Modelos de regressão logística bruta e ajustada foram construídos para analisar associações de métricas e escores do ICVH com diagnóstico de FFA. O nível de significância foi estabelecido em 0,05.

Resultados

A idade mediana da amostra foi de 55 anos, e 54,4% eram mulheres. Nos modelos ajustados, os escores de ICVH não apresentaram associação significativa com diagnóstico de FFA prevalente [odds ratio (OR):0,96; intervalo de confiança de 95% (IC95%):0,80-1,16; p=0,70). Perfis de pressão arterial ideal (OR:0,33; IC95%:0,1-0,74; p=0,007) e colesterol total ideal (OR:1,88; IC95%:1,19-2,98; p=0,007) foram significativamente associados com o diagnóstico de FFA.

Conclusões

Não foram identificadas associações significativas entre escores de ICVH global e diagnóstico de FFA após ajuste multivariado em nossas análises, devido, ao menos em parte, às associações antagônicas da FFA com métricas de pressão arterial e de colesterol total do ICVH. Nossos resultados sugerem que estimar a prevenção da FFA por meio de escore de ICVH global pode não ser adequado, e as métricas do ICVH devem ser consideradas separadamente.

Fibrilação Atrial; Flutter Atrial; Epidemiologia; Acidente Vascular Cerebral

Introduction

In 2010, the American Heart Association (AHA) set a decade-long goal to decrease cardiovascular disease (CVD) and stroke mortality by 20%.11. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, et al. Defining and Setting National Goals for Cardiovascular Health Promotion and Disease Reduction: The American Heart Association’s strategic Impact Goal through 2020 and Beyond. Circulation. 2010;121(4):586-613. doi: 10.1161/CIRCULATIONAHA.109.192703. The main strategy to achieve this goal included raising the prevalence of ideal cardiovascular profiles, measured by seven ideal cardiovascular health (ICVH) metrics: diet, physical activity, smoking, body mass index (BMI), blood pressure, fasting plasma glucose, and total cholesterol. The AHA established specific definitions for each of these metrics, as well as a ICVH score for an individual as the sum of the ideal profiles.

The effectiveness of such a strategy is subject to the strength of the associations between each ICVH metric and occurrence of fatal or non-fatal CVD. Some authors evaluated the association of the ICVH score and its components with subclinical CVD,22. Santos IS, Goulart AC, Pereira AC, Lotufo PA, Benseñor IM. Association between Cardiovascular Health Score and Carotid Intima-Media Thickness: Cross-Sectional Analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Baseline Assessment. J Am Soc Echocardiogr. 2016;29(12):1207-1216.e4. doi: 10.1016/j.echo.2016.09.001. clinical CVD33. Isiozor NM, Kunutsor SK, Voutilainen A, Kurl S, Kauhanen J, Laukkanen JA. Ideal Cardiovascular Health and Risk of Acute Myocardial Infarction Among Finnish Men. Atherosclerosis. 2019;289:126-131. doi: 10.1016/j.atherosclerosis.2019.08.024. and cardiovascular mortality.44. Corlin L, Short MI, Vasan RS, Xanthakis V. Association of the Duration of Ideal Cardiovascular Health Through Adulthood With Cardiometabolic Outcomes and Mortality in the Framingham Offspring Study. JAMA Cardiol. 2020;5(5):549-556. doi: 10.1001/jamacardio.2020.0109. A less studied cardiovascular condition in this context is atrial fibrillation or flutter (AFF). AFF has a lifetime risk of 25%,55. Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, et al. Lifetime Risk for Development of Atrial Fibrillation: The Framingham Heart Study. Circulation. 2004;110(9):1042-6. doi: 10.1161/01.CIR.0000140263.20897.42. is associated with multiple cardiovascular risk factors, and is a major risk factor for stroke, with population attributable fractions of stroke estimated between 2% and 6%.66. Kitamura A, Yamagishi K, Imano H, Kiyama M, Cui R, Ohira T, et al. Impact of Hypertension and Subclinical Organ Damage on the Incidence of Cardiovascular Disease Among Japanese Residents at the Population and Individual Levels - The Circulatory Risk in Communities Study (CIRCS). Circ J. 2017;81(7):1022-28. doi: 10.1253/circj.CJ-16-1129.

7. Nakayama T, Yokoyama T, Yoshiike N, Zaman MM, Date C, Tanaka H, et al. Population Attributable Fraction of Stroke Incidence in Middle-Aged and Elderly People: Contributions of Hypertension, Smoking and Atrial Fibrillation. Neuroepidemiology. 2000;19(4):217-26. doi: 10.1159/000026259.
- 88. Iwahana H, Ishikawa S, Ishikawa J, Kabutoya T, Kayaba K, Gotoh T, et al. Atrial Fibrillation is a Major Risk Factor for Stroke, Especially in Women: The Jichi Medical School Cohort Study. J Epidemiol. 2011;21(2):95-101. doi: 10.2188/jea.je20090149. Ogunmoroti et al.99. Ogunmoroti O, Michos ED, Aronis KN, Salami JA, Blankstein R, Virani SS, et al. Life’s Simple 7 and the Risk of Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2018;275:174-181. doi: 10.1016/j.atherosclerosis.2018.05.050. analyzed data from 6,506 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and found that individuals with an optimum ICVH score at the baseline had a 27% lower risk of AFF after a median follow-up of 11.2 years as compared to those with inadequate ICVH scores. Garg et al.1010. Garg PK, O’Neal WT, Chen LY, Loehr LR, Sotoodehnia N, Soliman EZ, et al. American Heart Association’s Life Simple 7 and Risk of Atrial Fibrillation in a Population Without Known Cardiovascular Disease: The ARIC (Atherosclerosis Risk in Communities) Study. J Am Heart Assoc. 2018;7(8):e008424. doi: 10.1161/JAHA.117.008424. analyzed data from 13,182 Atherosclerosis Risk in Communities (ARIC) participants and found that, after a follow-up of 25.1 years, each ideal component increase was associated with a 17% lower risk for AFF. Similar analyses were also performed by Garg et al. in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS),1111. Garg PK, O’Neal WT, Ogunsua A, Thacker EL, Howard G, Soliman EZ, et al. Usefulness of the American Heart Association’s Life Simple 7 to Predict the Risk of Atrial Fibrillation (from the REasons for Geographic And Racial Differences in Stroke [REGARDS] Study). Am J Cardiol. 2018;121(2):199-204. doi: 10.1016/j.amjcard.2017.09.033. resulting in a smaller (7%) although significant reduction in the risk for AFF for each ideal component increase. Recently, Lee et al.1212. Lee JH, Yang PS, Yu HT, Kim TH, Jang E, Uhm JS, et al. Association of Cardiovascular Health and Incident Atrial Fibrillation in Elderly Population. Heart. 2021:heartjnl-2020-318858. doi: 10.1136/heartjnl-2020-318858. analyzed 208,598 individuals who underwent national health check-up examinations in South Korea and found, after a median follow-up of 7.2 years, that ICVH scores were significantly associated with incident AFF.

Most information about the association between AFF and ICVH metrics and score come from large cohorts in the United States; however, 72% of global disability-adjusted life-years and 67% of deaths due to stroke were estimated to occur in countries with middle or low sociodemographic index in 2016.1313. GBD 2016 Stroke Collaborators. Global, Regional, and National Burden of Stroke, 1990-2016: A Systematic Analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(5):439-458. doi: 10.1016/S1474-4422(19)30034-1.
https://doi.org/10.1016/S1474-4422(19)30...
AFF is also common in Brazil, with a frequency of about 2% in primary care-based studies,1414. Santos JPAD, Ribeiro ALP, Andrade-Junior D, Marcolino MS. Prevalence of Electrocardiographic Abnormalities in Primary Care Patients According to Sex and Age Group. A Retrospective Observational Study. Sao Paulo Med J. 2018;136(1):20-8. doi: 10.1590/1516-3180.2017.0222290817. with higher frequencies associated with advancing age.

The aim of the present study is to report the associations between AFF diagnosis and ICVH metrics and score in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a Brazilian multicenter cohort study of individuals of 35-74 years of age at the baseline.

Methods

The ELSA-Brasil design1515. Aquino EM, Barreto SM, Bensenor IM, Carvalho MS, Chor D, Duncan BB, et al. Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): Objectives and Design. Am J Epidemiol. 2012;175(4):315-24. doi: 10.1093/aje/kwr294. and cohort profile1616. Schmidt MI, Duncan BB, Mill JG, Lotufo PA, Chor D, Barreto SM, et al. Cohort Profile: Longitudinal Study of Adult Health (ELSA-Brasil). Int J Epidemiol. 2015;44(1):68-75. doi: 10.1093/ije/dyu027. are detailed elsewhere. ELSA-Brasil is an ongoing multicenter cohort study in Brazil which enrolled 15,105 active or retired civil servants, from 35 to 74 years of age at baseline, from six institutions in six Brazilian cities. Baseline assessment occurred between August 2008 and December 2010. During this period, trained staff conducted in-person interviews, as well as clinical, laboratory, and imaging exams. After the baseline, all participants received a yearly telephone follow-up contact. From August 2012 to December 2014, all participants were invited to a second visit, during new questionnaires were administered, together with clinical and laboratory evaluations. A total of 14,014 (92.8%) individuals were reassessed. In the present article, information was obtained from the second visit, unless stated otherwise. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Institutional Review Boards of all institutions where ELSA-Brasil investigation centers are located. Informed consent was obtained from each participant.

Study sample

From 14,014 individuals who were present in the second onsite assessment, 505 individuals were excluded due to a lack of electrocardiographic (ECG) information and 368 participants due to missing information on ICVH metrics. Therefore, our main sample consisted of 13,141 individuals. For some sensitivity analyses, the sample was restricted to 12,307 individuals without previous self-reported myocardial infarction, stroke, or heart failure.

Data collection

ELSA-Brasil protocols1717. Mill JG, Pinto K, Griep RH, Goulart A, Foppa M, Lotufo PA, et al. Medical Assessments and Measurements in ELSA-Brasil. Rev Saude Publica. 2013;47 Suppl 2:54-62. doi: 10.1590/s0034-8910.2013047003851. , 1818. Fedeli LG, Vidigal PG, Leite CM, Castilhos CD, Pimentel RA, Maniero VC, et al. Logistics of Collection and Transportation of Biological Samples and the Organization of the Central Laboratory in the ELSA-Brasil. Rev Saude Publica. 2013;47 Suppl 2:63-71. doi: 10.1590/s0034-8910.2013047003807. for anthropometric, clinical and laboratory exams did not change between the first and second assessments. Age, sex, race, education level, and monthly family income were self-reported and stratified accordingly. Monthly income was analyzed as multiples of the Brazilian minimum wage (one Brazilian minimum wage during data collection averaged approximately 310 US dollars). Systolic and diastolic blood pressure (SBP and DBP, respectively) measurements were taken using a validated oscillometric device (Omron HEM 705CPINT). Three measurements were taken at one-minute intervals after a five-minute rest with the subject in the sitting position, and the average of the second and third measurements was considered to define SBP and DBP. Fasting plasma glucose was determined using the hexokinase method and total cholesterol using the cholesterol oxidase method, conducted in an ADVIA 1200 Siemens® equipment.

AFF diagnosis

ECG recordings in ELSA-Brasil were obtained as described elsewhere.1919. Pinto MM Filho, Brant LCC, Silva JLP, Foppa M, Lotufo PA, Mill JG, et al. Electrocardiographic Findings in Brazilian Adults without Heart Disease: ELSA-Brasil. Arq Bras Cardiol. 2017;109(5):416-24. doi: 10.5935/abc.20170146. , 2020. Santos IS, Lotufo PA, Brant LCC, Pinto MM Filho, Pereira ADC, Barreto SM, et al. Atrial Fibrillation Diagnosis using ECG Records and Self-Report in the Community: Cross-Sectional Analysis from ELSA-Brasil. Arq Bras Cardiol. 2021;117(3):426-434. doi: 10.36660/abc.20190873. Electrocardiography in onsite assessments was performed using a Burdick Atria 6100 device, calibrated at 10 mm/mV and a speed of 25 mm/second. The recordings were transmitted to the reading center in the Minas Gerais Investigation Center. Analyses followed the Glasgow system and were coded according to the Minnesota Coding System. Selected codes (including AFF) were manually reviewed by trained staff. These methods have been adopted in all ELSA-Brasil assessments to date. AFF diagnosis in this article was defined as its presence in ECG tracing at the baseline or on the second visit.

ICVH score

Detailed information about the ideal ICVH scoring in ELSA-Brasil can be found elsewhere.2121. Machado LBM, Silva BLS, Garcia AP, Oliveira RAM, Barreto SM, Fonseca MJM, et al. Ideal Cardiovascular Health Score at the ELSA-Brasil Baseline and its Association with Sociodemographic Characteristics. Int J Cardiol. 2018;254:333-337. doi: 10.1016/j.ijcard.2017.12.037. The following definitions were used for the seven ICVH metrics, based on the AHA guidelines:11. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, et al. Defining and Setting National Goals for Cardiovascular Health Promotion and Disease Reduction: The American Heart Association’s strategic Impact Goal through 2020 and Beyond. Circulation. 2010;121(4):586-613. doi: 10.1161/CIRCULATIONAHA.109.192703.

  1. Diet: Four adequate components from (a) ≥ 4 servings of fruit and vegetables per day, (b) ≥ 7 ounces of fish per week, (c) ≥ 2 servings of fiber-rich whole grains per day, (d) ≤ 450 kcal of sugar-sweetened beverages per week, and (e) sodium consumption ≤ 1500 mg/day;

  2. Physical activity: ≥ 75 minutes/week of vigorous physical activity, or ≥ 150 minutes/week of moderate physical activity, or ≥ 150 minutes/week of moderate + vigorous physical activity;

  3. Smoking: never smoked or former smoker age upon quitting of at least two years less than the age at onsite assessment;

  4. BMI < 25 kg/m22. Santos IS, Goulart AC, Pereira AC, Lotufo PA, Benseñor IM. Association between Cardiovascular Health Score and Carotid Intima-Media Thickness: Cross-Sectional Analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Baseline Assessment. J Am Soc Echocardiogr. 2016;29(12):1207-1216.e4. doi: 10.1016/j.echo.2016.09.001. ;

  5. Blood pressure: SBP < 120 mmHg and DBP < 80 mmHg, without antihypertensive medication;

  6. Fasting plasma glucose: < 100 mg/dL, without hypoglycemic medication;

  7. Total cholesterol: < 200 mg/dl, without lipid-lowering medication.

All information for ICVH scoring was obtained from the second visit, except for the diet ICVH metric. The diet ICVH metric was evaluated using information from the complete food frequency questionnaire, which was applied in the ELSA-Brasil baseline. The global ICVH score was calculated as the sum of the ideal profiles (range: 0 to 7 points). Scores of participants’ lifestyle (diet, physical activity, smoking, and BMI; range 0-4) and health (blood pressure, fasting plasma glucose, and total cholesterol; range 0-3) were evaluated separately.

Statistical analysis

Categorical variables were presented as counts and proportions, and continuous variables were presented as medians and interquartile ranges. Normality of data was evaluated using density plots and the Anderson-Darling test. We calculated the sensitivity and specificity of different cutoffs for global ICVH score to classify individuals with and without AFF in the sample. We plotted a receiver-operating characteristic (ROC) curve using these values and calculated the area under the ROC curve (AUROC) to estimate the discriminative capacity of the global ICVH scores to identify individuals with AFF in this setting. Binary logistic regression models were built to analyze the association of ICVH metrics and global, lifestyle, and health scores with AFF diagnosis. These models are presented in their crude form and adjusted for age, sex, and race. Sensitivity analyses were performed, restricting the sample to the individuals without previous self-reported myocardial infarction, stroke, or heart failure. After observing a paradoxical association between the total cholesterol ICVH metric and AFF, we ran some analyses a posteriori, (1) excluding individuals under statin use, as some authors pointed a potential benefit of statins on incident atrial fibrillation;2222. Hung CY, Lin CH, Wang KY, Huang JL, Hsieh YC, Loh el-W, ET AL. Dosage of Statin, Cardiovascular Comorbidities, and Risk of Atrial Fibrillation: A Nationwide Population-Based Cohort Study. Int J Cardiol. 2013;168(2):1131-6. doi: 10.1016/j.ijcard.2012.11.087. , 2323. Fauchier L, Clementy N, Babuty D. Statin Therapy and Atrial Fibrillation: Systematic Review and Updated Meta-Analysis of Published Randomized Controlled Trials. Curr Opin Cardiol. 2013;28(1):7-18. doi: 10.1097/HCO.0b013e32835b0956. (2) excluding the total cholesterol ICVH metric from the global and health ICVH scores. The crude and adjusted binary logistic regression models were also presented in order to analyze the association between these modified scores and AFF diagnosis. Analyses were performed using R software, version 4.0.0. The significance level was set at 5%.

Results

Table 1 summarizes the characteristics of the sample. Median age was 55 years and 7,147 (54.4%) were women. Most participants were of white race, had a college education and a family income between six and 15 Brazilian minimum wages (approximately 1,860 to 4,650 US dollars/month). AFF in ECG tracings was detected in 80 (0.6%) participants. The most frequent ICVH metric was smoking, present in 11,548 (87.9%) participants. Supplemental Table 1 shows the characteristics of study participants after excluding those with previous self-reported myocardial infarction, stroke, or heart failure.

Table 1
Characteristics of the study sample

Supplemental Figure 1 shows the ROC curve addressing the accuracy of global ICVH scores in identifying individuals with AFF in the sample. The AUROC is 0.59, indicating a relatively low discriminatory power of global ICVH scores in this scenario. More details are shown in the Supplemental Table 2 , which displays sensitivity and specificity values for different global ICVH score cutoffs.

Table 2
Odds ratios (95% CI) for the association between ICVH scores and metrics and atrial fibrillation or flutter diagnosis

Table 2 shows the odds ratios (OR) and respective 95% confidence intervals (95%CI) for the association of ICVH scores and metrics with prevalent AFF. In the entire sample, ICVH scores were inversely associated with AFF diagnosis in crude models (p=0.012), although this association disappeared vanished after adjustment for age, sex, and race (p=0.70). No lifestyle ICVH metric nor the lifestyle ICVH score was significantly associated with AFF. The blood pressure ICVH metric was inversely associated with AFF in both crude (p<0.001) and adjusted (p=0.007) models. There was a paradoxical positive association between the total cholesterol ICVH profile and AFF in the adjusted models (p=0.007). The exclusion of individuals under statin use from analyses led to a loss of significance for the association between the total cholesterol ICVH profile and AFF in the adjusted models (OR: 2.22; 95%CI: 0.86 - 5.70; p=0.098). However, this loss of significance seems to be primarily due to a lack of statistical power, as 46.2% of participants with AFF and 51.0% of participants without AFF were under statins.

As the associations of AFF with blood pressure and total cholesterol ICVH metrics were antagonistic, AFF was not associated with an overall health ICVH score in adjusted models (p=0.76). After excluding individuals with self-reported myocardial infarction, stroke, or heart failure, the associations between AFF and blood pressure (p=0.023) and total cholesterol ICVH metrics (p=0.007) in adjusted models remained.

We also verified whether the global and/or health ICVH scores were associated with AFF after the exclusion of the total cholesterol ICVH metric. The global ICVH score was shown to be inversely associated with an AFF diagnosis in crude models (OR: 0.70; 95% CI: 0.57 – 0.86; p=0.001) with a non-significant trend towards an inverse association in adjusted models (OR: 0.84; 95% CI: 0.67 – 1.04; p=0.11). Health ICVH scores were inversely associated with an AFF diagnosis in both crude (OR: 0.41; 95% CI: 0.28 – 0.59; p<0.001) and adjusted (OR: 0.63; 95% CI: 0.42 – 0.93; p=0.020) models.

Discussion

In the ELSA-Brasil sample, global ICVH scores were associated with prevalent AFF in crude models. However, they were associated with low AUROC values and statistical significance disappeared in models adjusted for age, sex, and race. Analyzing ICVH metrics separately, a strong inverse association was found between the blood pressure ICVH metric and AFF. A positive but paradoxical association was observed between the total cholesterol ICVH metric and AFF: an ideal total cholesterol ICVH metric was associated with AFF diagnosis. The restriction of the sample to individuals with no self-reported myocardial infarction, stroke, or heart failure yielded similar results. The exclusion of the total cholesterol ICVH metric led to a significant inverse association between health ICVH scores and AFF.

The importance of hypertension as a risk factor for AFF is well defined in the literature. In a systematic review of risk factors for incident AFF, Allan et al.2424. Allan V, Honarbakhsh S, Casas JP, Wallace J, Hunter R, Schilling R, et al. 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. Thromb Haemost. 2017;117(5):837-850. doi: 10.1160/TH16-11-0825. reviewed data from 32 population-based cohorts, including more than 20 million subjects. The authors found that the diagnosis of hypertension and high systolic blood pressure were consistently associated with incident AFF. Recently, Rattani et al.2525. Rattani A, Claxton JS, Ali MK, Chen LY, Soliman EZ, Alvaro A. Association and Impact of Hypertension Defined Using the 2017 AHA/ACC Guidelines on the Risk of Atrial Fibrillation in The Atherosclerosis Risk in Communities study. BMC Cardiovasc Disord. 2019;19(1):262. doi: 10.1186/s12872-019-1259-0. used data from the ARIC study to calculate the population attributable risk of hypertension for AFF. The authors defined hypertension according to the criteria from the 7th Report of the Joint National Committee (≥140/90 mmHg) and the 2017 American Heart Association/American College of Cardiology guidelines (≥130/80 mmHg), and found population attributed fraction values of 11% and 13%, respectively. Expectedly, the presence of an ideal blood pressure profile was also inversely associated with AFF in the ARIC,1010. Garg PK, O’Neal WT, Chen LY, Loehr LR, Sotoodehnia N, Soliman EZ, et al. American Heart Association’s Life Simple 7 and Risk of Atrial Fibrillation in a Population Without Known Cardiovascular Disease: The ARIC (Atherosclerosis Risk in Communities) Study. J Am Heart Assoc. 2018;7(8):e008424. doi: 10.1161/JAHA.117.008424. REGARDS,1111. Garg PK, O’Neal WT, Ogunsua A, Thacker EL, Howard G, Soliman EZ, et al. Usefulness of the American Heart Association’s Life Simple 7 to Predict the Risk of Atrial Fibrillation (from the REasons for Geographic And Racial Differences in Stroke [REGARDS] Study). Am J Cardiol. 2018;121(2):199-204. doi: 10.1016/j.amjcard.2017.09.033. and MESA99. Ogunmoroti O, Michos ED, Aronis KN, Salami JA, Blankstein R, Virani SS, et al. Life’s Simple 7 and the Risk of Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2018;275:174-181. doi: 10.1016/j.atherosclerosis.2018.05.050. cohort studies.

Although total cholesterol (mainly due to its main subfraction, LDL-c) is a major risk factor for atherosclerotic cardiovascular disease, its association with AFF is much less clear. Other authors have pointed to the cholesterol paradox in AFF, describing lower cholesterol levels in individuals with AFF, upon comparing controls in diverse scenarios, such as individuals treated in referral centers for other cardiovascular diseases, those treated in primary care units,2626. Annoura M, Ogawa M, Kumagai K, Zhang B, Saku K, Arakawa K. Cholesterol Paradox in Patients with Paroxysmal Atrial Fibrillation. Cardiology. 1999;92(1):21-7. doi: 10.1159/000006942. , 2727. Mourtzinis G, Kahan T, Boström KB, Schiöler L, Wallin LC, Hjerpe P, et al. Relation Between Lipid Profile and New-Onset Atrial Fibrillation in Patients with Systemic Hypertension (From the Swedish Primary Care Cardiovascular Database [SPCCD]). Am J Cardiol. 2018;122(1):102-107. doi: 10.1016/j.amjcard.2018.03.024. or even those from community samples.2828. Lee HJ, Lee SR, Choi EK, Han KD, Oh S. Low Lipid Levels and High Variability are Associated with the Risk of New-Onset Atrial Fibrillation. J Am Heart Assoc. 2019;8(23):e012771. doi: 10.1161/JAHA.119.012771. In a recent systematic review, Guan et al.2929. Guan B, Li X, Xue W, Tse G, Waleed KB, Liu Y, et al. Blood Lipid Profiles and Risk of Atrial Fibrillation: A Systematic Review and Meta-Analysis of Cohort Studies. J Clin Lipidol. 2020;14(1):133-142.e3. doi: 10.1016/j.jacl.2019.12.002. found that high levels of total cholesterol (defined at cutoffs between 220 and 260 mg/dL across studies, or based on the empirical distribution within the sample) were associated with a pooled hazard ratio for AFF of 0.81 (95% CI: 0.72-0.92), which was consistent with our findings. In the same systematic review, analyses using LDL-C instead of total cholesterol levels yielded similar results.

There is some evidence that statins may have a potential benefit on incident atrial fibrillation.2222. Hung CY, Lin CH, Wang KY, Huang JL, Hsieh YC, Loh el-W, ET AL. Dosage of Statin, Cardiovascular Comorbidities, and Risk of Atrial Fibrillation: A Nationwide Population-Based Cohort Study. Int J Cardiol. 2013;168(2):1131-6. doi: 10.1016/j.ijcard.2012.11.087. , 2323. Fauchier L, Clementy N, Babuty D. Statin Therapy and Atrial Fibrillation: Systematic Review and Updated Meta-Analysis of Published Randomized Controlled Trials. Curr Opin Cardiol. 2013;28(1):7-18. doi: 10.1097/HCO.0b013e32835b0956. However, the ICVH metric considers as a non-ideal profile if the individual is under lipid-lowering medications, regardless of his/her total cholesterol levels. Therefore, it could be argued that the paradoxical association between total cholesterol ICVH profile and AFF is explained by statin use. Our data suggest this is not the case. The proportion of individuals in our sample using lipid-lowering medication is similar. Moreover, although the exclusion of individuals under statins led to a loss of statistical significance, this was probably due to the high number of exclusions from this sensitivity analysis (51.0% of our sample), as the OR point estimates were also similar (1.88 for the whole sample; 2.22 after excluding those using lipid-lowering medication)

The criterion used as the total cholesterol ICVH metric (<200 mg/dL without lipid-lowering medication use) is stricter than those in the studies included in this systematic review. The cohort studies99. Ogunmoroti O, Michos ED, Aronis KN, Salami JA, Blankstein R, Virani SS, et al. Life’s Simple 7 and the Risk of Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2018;275:174-181. doi: 10.1016/j.atherosclerosis.2018.05.050.

10. Garg PK, O’Neal WT, Chen LY, Loehr LR, Sotoodehnia N, Soliman EZ, et al. American Heart Association’s Life Simple 7 and Risk of Atrial Fibrillation in a Population Without Known Cardiovascular Disease: The ARIC (Atherosclerosis Risk in Communities) Study. J Am Heart Assoc. 2018;7(8):e008424. doi: 10.1161/JAHA.117.008424.
- 1111. Garg PK, O’Neal WT, Ogunsua A, Thacker EL, Howard G, Soliman EZ, et al. Usefulness of the American Heart Association’s Life Simple 7 to Predict the Risk of Atrial Fibrillation (from the REasons for Geographic And Racial Differences in Stroke [REGARDS] Study). Am J Cardiol. 2018;121(2):199-204. doi: 10.1016/j.amjcard.2017.09.033. that evaluated ICVH scores and their relationship with AFF diagnosis have also studied the total cholesterol ICVH metric separately. In all cases, the hazard point estimates suggested higher odds for AFF in individuals with ideal total cholesterol, but without statistical significance. Their non-significant results contrast to our finding of a significant, positive, but paradoxical association between the total cholesterol ICVH metric and AFF diagnosis in adjusted models. This significant association in our study was evident even with less AFF cases in the sample, when compared to these previous publications. Differences in study populations and design may be partly responsible for this discrepancy. Similar to the United States, black Brazilians have a higher prevalence of hypertension3030. Chor D, Ribeiro APL, Carvalho MS, Duncan BB, Lotufo PA, Nobre AA, et al. Prevalence, Awareness, Treatment and Influence of Socioeconomic Variables on Control of High Blood Pressure: Results of the ELSA-Brasil Study. PLoS One. 2015;10(6):e0127382. doi: 10.1371/journal.pone.0127382. and a lower prevalence of dyslipidemia,3131. Santos RD, Bensenor IM, Pereira AC, Lotufo PA. Dyslipidemia According to Gender and Race: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). J Clin Lipidol. 2016;10(6):1362-1368. doi: 10.1016/j.jacl.2016.08.008. when compared to white Brazilians. It could be argued, given the strong inverse association between blood pressure and AFF, that race could be a confounder in the positive association between a total cholesterol ICVH profile and AFF diagnosis. However, it is important to note that our results were maintained even after adjustment for race. Future longitudinal analyses from the ELSA-Brasil, including the occurrence of more AFF cases, will clarify if the cholesterol paradox in individuals with AFF is particularly strong in the Brazilian population.

In 2018, Isakadze et al.3232. Isakadze N, Pratik B, Sandesara B, Patel R, Baer J, Isiadinso I, et al. Life’s Simple 7 Approach to Atrial Fibrillation Prevention. J Atr Fibrillation. 2018;11(3):2051. doi: 10.4022/jafib.2051. proposed that the use of the ICVH score to improve overall cardiovascular health may substantially reduce AFF prevalence. Although current evidence suggests this is probably true, our results and previous data also point out that individual ICVH metrics may have different (and even antagonistic) effects on AFF prevalence. Therefore, it is arguable that the progress in AFF prevention resulting from improvements in ICVH scores must be estimated considering not only the impact of all ICVH metrics together but also of each metric separately.

The present study has strengths. First, it evaluated data from a large sample in Brazil. To our knowledge, this is the first study to analyze the association between AFF and ICVH metrics in a South American sample with different characteristics compared to the samples analyzed in previous studies. ECG tracings were also analyzed in a centralized reading center, using a standardized protocol,1919. Pinto MM Filho, Brant LCC, Silva JLP, Foppa M, Lotufo PA, Mill JG, et al. Electrocardiographic Findings in Brazilian Adults without Heart Disease: ELSA-Brasil. Arq Bras Cardiol. 2017;109(5):416-24. doi: 10.5935/abc.20170146. and the ICVH score criteria could be applied with minimal adaptations.

This study also needs to be interpreted in the context of its limitations. The sample of this study included a small number of AFF participants. This is most probably due to its high proportion of individuals of less than 60 years of age. As time progresses, incident AFF cases may increase the power of our analyses. This may have influenced our finding of non-association between AFF diagnosis and ICVH scores. The food frequency questionnaire was not applied in the second visit of patients in the ELSA-Brasil; therefore, it was considered that participants maintained their diet ICVH status after the baseline. The prevalence of an ICVH diet was very low in the ELSA-Brasil baseline (1.3%),2121. Machado LBM, Silva BLS, Garcia AP, Oliveira RAM, Barreto SM, Fonseca MJM, et al. Ideal Cardiovascular Health Score at the ELSA-Brasil Baseline and its Association with Sociodemographic Characteristics. Int J Cardiol. 2018;254:333-337. doi: 10.1016/j.ijcard.2017.12.037. which is consistent with the findings from other populations.3333. Younus A, Aneni EC, Spatz ES, Osondu CU, Roberson L, Ogunmoroti O, et al. A Systematic Review of the Prevalence and Outcomes of Ideal Cardiovascular Health in US and Non-US Populations. Mayo Clin Proc. 2016;91(5):649-70. doi: 10.1016/j.mayocp.2016.01.019. Therefore, it is unlikely that a large proportion of participants would have adopted an ideal diet between the baseline and the second onsite assessment. The AFF was defined based only on ECG tracings of the ELSA-Brasil and, although this ensures high specificity, paroxysmal AFF may be underrepresented in our analyses.

Conclusions

In conclusion, no significant associations were observed between global ICVH scores and AFF diagnosis in our analyses, at least partially due to antagonistic associations of AFF with blood pressure and total cholesterol. Our results suggest that estimating the AFF prevention effect using global ICVH scores may not be adequate, and ICVH metrics should be considered in separate.

Acknowledgements

The ELSA-Brasil baseline study was supported by the Brazilian Ministry of Health (Science and Technology Department) and the Brazilian Ministry of Science, Technology and Innovation (Funder of studies and projects and CNPq National Research Council) (grants 01 06 0010.00 RS, 01 06 0212.00 BA, 01 06 0300.00 ES, 01 06 0278.00 MG, 01 06 0115.00 SP, 01 06 0071.00 RJ). ALR was supported in part by CNPq (grant 310679/2016–8), Instituto de Avaliação de Tecnologia em Saúde (IATS, grant 465518/2014–1) and by FAPEMIG (Programa Pesquisador Mineiro, PPM-00 428–17). This research was also funded by the National Institute for Health Research (project reference 17/63/121, the NIHR Global Health Research Group on Atrial Fibrillation Management).

* Supplemental Materials

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  • Study Association
    This study is not associated with any thesis or dissertation work.
  • Ethics approval and consent to participate
    This study was approved by the Ethics Committee of the Hospital Universitário da USP under the protocol number 659/06. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.
  • Sources of Funding: This study was partially funded by Brazilian Ministry of Health, Brazilian Ministry of Science and Technology, National Institute for Health Research.

Publication Dates

  • Publication in this collection
    15 Sept 2022
  • Date of issue
    Nov 2022

History

  • Received
    21 Nov 2021
  • Reviewed
    13 Mar 2022
  • Accepted
    01 June 2022
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