Associations of serum n-3 and n-6 PUFA and hair mercury with the risk of incident stroke in men: the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD)

Abstract

PUFA have been associated with lower risk of CVD, but less is known about their association with stroke risk. Fish, a major source of n-3 PUFA, may also contain methylmercury, which has been associated with higher risk of CVD and attenuation of the benefits of long-chain n-3 PUFA. We investigated the associations of serum n-3 and n-6 PUFA and hair Hg with risk of stroke in men. A total of 1828 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years and free of CVD at baseline in 1984-1989 were studied. Cox regression models were used for the analyses. During the mean follow-up of 21·2 years, 202 stroke cases occurred, of which 153 were ischaemic strokes. After adjustment for age and examination year, the only statistically significant association among the n-3 and n-6 PUFA was observed between the n-3 PUFA α-linolenic acid and risk of haemorrhagic stroke (hazard ratio in the highest v. the lowest quartile 0·33; 95 % CI 0·13, 0·86; P trend = 0·03). However, further adjustments attenuated the association to statistically non-significant. Hair Hg was not associated with stroke risk, but among those with hair Hg above the median level, higher serum long-chain n-3 PUFA concentrations were associated with a higher risk of ischaemic stroke. In our cohort of men, serum n-3 or n-6 PUFA or hair Hg were not associated with stroke risk; however, the interaction between Hg and long-chain n-3 PUFA with regard to ischaemic stroke risk warrants further investigation.

Associations of estimated Δ-5-desaturase and Δ-6-desaturase activities with stroke risk factors and risk of stroke: the Kuopio Ischaemic Heart Disease Risk Factor Study

“…Especially the association with one of the strongest risk factors for stroke, high blood pressure, was quite modest and may not be clinically significant. The lack of association with the desaturase activities in the current study is also supported by the similar lack of association of the serum n -3 and n -6 PUFA with the risk of stroke in this study population ( 28 ) .…”

“…All quantitative variables were entered as continuous variables. The covariates in the models were chosen to comply with recent analyses regarding the n -3 and n -6 PUFA and risk of stroke in this study population ( 28 ) . Further adjustment for the potential confounders education and waist circumference did not appreciably change the associations (change in estimates <5 %).…”

Circulating long-chain n-3 polyunsaturated fatty acid and incidence of stroke: a meta-analysis of prospective cohort studies

“…Over the 11 years of median follow-up duration, which ranged from 4.7 to 29.3 years, a total of 2,836 stroke events occurred among 20,460 individuals aged 35–79 yr from Europe and US (Table 1 ). Among the 10 included studies, 5 studies were conducted in USA [ 8 – 12 ] and 5 in Europe [ 13 – 17 ]. Circulating total LC n-3 PUFA as a biomarker was provided in 9 studies [ 8 – 17 ], 20:5n-3 in 8 studies [ 8 – 13 , 16 , 17 ], 22:5n-3 in 6 studies [ 8 – 10 , 12 , 16 , 17 ], and 22:6n-3 in 8 studies [ 8 – 13 , 16 , 17 ].…”

“…The proportions of LC n-3 PUFA in blood samples were quantified by gas liquid chromatography (GLC). One study separately included males (M) and females (F) [ 14 ], 3 articles only M [ 9 , 13 , 17 ], 1 study [ 10 ] only F and 5 studies included both M and F. Study quality assessed by the 9-star Newcastle-Ottawa Scale (NOS) ranged from 6 to 8, with a median of 7. All included studies provided relative risk (RR) that was controlled for age, gender, smoking and alcohol intake, 8 studies adjusted for lifestyle plus traditional cardiovascular disease (CVD) risk factors [ 8 , 10 – 15 , 17 ], and 3 studies additionally adjusted for dietary intakes [ 8 , 10 , 12 ].…”

“…Overall, 6 eligible studies were available to evaluate a dose-response association between circulating LC n-3 PUFA and risk of stroke [ 8 , 10 – 12 , 16 , 17 ]. No significantly curvilinear (nonlinear) association was observed through a test for non-linearity ( P for nonlinearity = 0.40) (Figure 4A ), but the association was significant in a linear dose-response model ( P for trend = 0.02), with a 1% increment of LC n-3 PUFA proportions in circulating blood associated with 5% reduced risk of stroke (SRR = 0.95; 95% CI: 0.92, 0.98; I 2 = 14.90%) ( Supplementary Figure 8 ).…”