Fatty Acids and AF in Patients With Chronic Heart Failure
Fatty Acids and AF in Patients With Chronic Heart Failure
Of the 6975 patients from the GISSI-HF trial randomized to n-3 PUFAs or placebo, 1140 (16.3%) had AF in the baseline ECG and were excluded from the analysis of incident AF. For the present study, we analysed the data of 5835 patients without AF at baseline ECG (5082 in sinus rhythm and 753 with pacemaker-induced rhythm). The patients from this cohort were aged 66 ± 11 years and more than a fifth were females. The mean (SD) LVEF was 32.6 ± 8.1%, and 66% of the patients were in NYHA class II. Ischaemic heart disease and dilative cardiomyopathy were the causes of HF in 82%. At baseline, most of the patients were on treatment with ACE inhibitors or ARBs, and 67% were taking beta-blockers. Other clinical and laboratory characteristics are listed by study treatment in the Supplementary material, Table S1.
At baseline, more frequent fish consumption was associated with a lower prevalence of AF in univariate analysis (P for trend = 0.008). For instance, 2060 out of the 6975 patients who ate fish twice a week had a 18% lower risk of prevalent AF than the 1753 who almost never ate fish (P = 0.025). However, at logistic fully adjusted regression analysis, fish intake was not independently associated with prevalent AF. The plasma levels of n-3 PUFAs at baseline were available for 1203 of the 6975 patients from 51 centres. The prevalence of AF fell with increasing levels of n-3 PUFAs (Figure 1). At univariate analysis, the 404 patients in the lowest tertile (≤4.32 mol%) had a two-fold higher risk of AF than those in the highest tertile (>5.43 mol%). This was also true after full adjustment for significant demographic and clinical variables (OR 1.84, 95% CI 1.15–2.95, P = 0.012).
(Enlarge Image)
Figure 1.
Prevalence of AF at study entry by circulating levels of n-3 polyunsturated fatty acids (PUFAs) in 1203 patients of the GISSI-HF trail. Plasma levels of n-3 PUFAs were measured at study entry and divided into tertiles. Logistic analysis were adjusted as described in the Methods.
During the follow-up period of 3.9 (Q1–Q3: 3.0–4.5) years, AF occurred in 852 (14.6%) of the 5835 patients without AF at study entry. The patients with incident AF were older, had higher body mass index, and more frequently had co-morbidities such as anaemia, COPD, stroke, and chronic renal failure. They also had higher hospital admission rates in the year before randomization, and tended to be in a more advanced NYHA class and to have a history of paroxysmal AF (Table 1).
Among the 852 (14.6%) patients developing AF during the trial, 444 were in the group of 2921 patients randomized to n-3 PUFAs (15.2%) and 408 in the 2914 allocated to placebo (14.0%) (unadjusted HR 1.10, 95% CI 0.96–1.25, P = 0.19). Figure 2 shows the Kaplan–Meier curves for incident AF by treatment. The same univariate analysis was run (Table 2) after exclusion of (i) patients with a history of AF (population #2) and (ii) those with a history of AF and with pacemaker rhythm at baseline ECG (population #3); n-3 PUFAs significantly increased the incidence of AF in population 3 (unadjusted HR 1.23, 95% CI 1.02–1.48, P = 0.03). In the subgroup analysis performed on 5835 patients without AF at study entry, there was no significant interaction between n-3 PUFA randomization and incident AF by age, LVEF, HF aetiology, NYHA functional class, history of diabetes, cholesterol, renal function, history of paroxysmal AF, or dietary fish consumption (Supplementary material, Table S2).
(Enlarge Image)
Figure 2.
Kaplan–Meier curves for time to new onset of AF in the n-3 polyunsturated fatty acid (PUFA) and placebo groups.
At multivariable analysis adjusted for clinical variables, laboratory tests, and background pharmacological therapy, the five variables most strongly related to incident AF were history of paroxysmal AF (HR 3.35, 95% CI 2.81–4.00, P < 0.0001), advanced age (HR 1.03, 95% CI 1.02–1.04, P < 0.0001), higher body mass index (HR 1.04, 95% CI 1.02–1.06, P < 0.0001), anticoagulation therapy (HR 1.90, 95% CI 1.49–2.42, P < 0.0001), and diuretics (HR 1.72, 95% CI 1.22–2.43, P = 0.002). Neither dietary fish consumption nor plasma concentrations of n-3 PUFAs were independently associated with incident AF.
Results
Of the 6975 patients from the GISSI-HF trial randomized to n-3 PUFAs or placebo, 1140 (16.3%) had AF in the baseline ECG and were excluded from the analysis of incident AF. For the present study, we analysed the data of 5835 patients without AF at baseline ECG (5082 in sinus rhythm and 753 with pacemaker-induced rhythm). The patients from this cohort were aged 66 ± 11 years and more than a fifth were females. The mean (SD) LVEF was 32.6 ± 8.1%, and 66% of the patients were in NYHA class II. Ischaemic heart disease and dilative cardiomyopathy were the causes of HF in 82%. At baseline, most of the patients were on treatment with ACE inhibitors or ARBs, and 67% were taking beta-blockers. Other clinical and laboratory characteristics are listed by study treatment in the Supplementary material, Table S1.
Prevalent Atrial Fibrillation
At baseline, more frequent fish consumption was associated with a lower prevalence of AF in univariate analysis (P for trend = 0.008). For instance, 2060 out of the 6975 patients who ate fish twice a week had a 18% lower risk of prevalent AF than the 1753 who almost never ate fish (P = 0.025). However, at logistic fully adjusted regression analysis, fish intake was not independently associated with prevalent AF. The plasma levels of n-3 PUFAs at baseline were available for 1203 of the 6975 patients from 51 centres. The prevalence of AF fell with increasing levels of n-3 PUFAs (Figure 1). At univariate analysis, the 404 patients in the lowest tertile (≤4.32 mol%) had a two-fold higher risk of AF than those in the highest tertile (>5.43 mol%). This was also true after full adjustment for significant demographic and clinical variables (OR 1.84, 95% CI 1.15–2.95, P = 0.012).
(Enlarge Image)
Figure 1.
Prevalence of AF at study entry by circulating levels of n-3 polyunsturated fatty acids (PUFAs) in 1203 patients of the GISSI-HF trail. Plasma levels of n-3 PUFAs were measured at study entry and divided into tertiles. Logistic analysis were adjusted as described in the Methods.
Incident Atrial Fibrillation
During the follow-up period of 3.9 (Q1–Q3: 3.0–4.5) years, AF occurred in 852 (14.6%) of the 5835 patients without AF at study entry. The patients with incident AF were older, had higher body mass index, and more frequently had co-morbidities such as anaemia, COPD, stroke, and chronic renal failure. They also had higher hospital admission rates in the year before randomization, and tended to be in a more advanced NYHA class and to have a history of paroxysmal AF (Table 1).
Among the 852 (14.6%) patients developing AF during the trial, 444 were in the group of 2921 patients randomized to n-3 PUFAs (15.2%) and 408 in the 2914 allocated to placebo (14.0%) (unadjusted HR 1.10, 95% CI 0.96–1.25, P = 0.19). Figure 2 shows the Kaplan–Meier curves for incident AF by treatment. The same univariate analysis was run (Table 2) after exclusion of (i) patients with a history of AF (population #2) and (ii) those with a history of AF and with pacemaker rhythm at baseline ECG (population #3); n-3 PUFAs significantly increased the incidence of AF in population 3 (unadjusted HR 1.23, 95% CI 1.02–1.48, P = 0.03). In the subgroup analysis performed on 5835 patients without AF at study entry, there was no significant interaction between n-3 PUFA randomization and incident AF by age, LVEF, HF aetiology, NYHA functional class, history of diabetes, cholesterol, renal function, history of paroxysmal AF, or dietary fish consumption (Supplementary material, Table S2).
(Enlarge Image)
Figure 2.
Kaplan–Meier curves for time to new onset of AF in the n-3 polyunsturated fatty acid (PUFA) and placebo groups.
At multivariable analysis adjusted for clinical variables, laboratory tests, and background pharmacological therapy, the five variables most strongly related to incident AF were history of paroxysmal AF (HR 3.35, 95% CI 2.81–4.00, P < 0.0001), advanced age (HR 1.03, 95% CI 1.02–1.04, P < 0.0001), higher body mass index (HR 1.04, 95% CI 1.02–1.06, P < 0.0001), anticoagulation therapy (HR 1.90, 95% CI 1.49–2.42, P < 0.0001), and diuretics (HR 1.72, 95% CI 1.22–2.43, P = 0.002). Neither dietary fish consumption nor plasma concentrations of n-3 PUFAs were independently associated with incident AF.
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