In this large cohort of women, those who drank moderate to high amounts of coffee had a lower risk of stroke than those who did not consume coffee. This association was only partially mediated by potential biological mediators including high blood pressure, hypercholesterolemia, and type 2 diabetes mellitus. Higher consumption of decaffeinated coffee, but not tea or caffeinated soft drinks was also associated with a generally lower stroke risk, supporting the hypothesis that components in coffee other than caffeine may lower risk of stroke.
Few studies have addressed the association between coffee consumption and risk of stroke (). Those analyses have been performed in groups with very different risk of stroke, such as healthy people, patients with type 2 diabetes, hypertensive individuals, and even smokers. In our analyses, we were able to assess long-term coffee consumption in a large population of women and evaluate possible differences in association between healthy participants and those with the above vascular risk factors.
Cohort studies addressing the association between caffeinated coffee consumption and risk of stroke.a
Hypertension is a major risk factor for stroke. 13
However, the relationship between long-term coffee consumption and hypertension remains uncertain because few cohort studies have analyzed this association. Klag et al., 14
using the Johns Hopkins Precursors Study, found that consumption of coffee was cross-sectionally associated with a slightly higher blood pressure, although the association with incident hypertension was unclear. Winkelmayer et al., 30
using data from the Nurses' Health Study and Nurses' Health Study II, found that coffee consumption was not associated with an increased risk of hypertension in women [RR (95% CI) for consumption of ≥6 cups/d: 0.88 (0.80-0.98) vs. <1 cup/d in NHS, and 0.91 (0.80-1.04) in NHS II]. Hu et al. 31
examined the association between coffee and the incidence of antihypertensive drug use. The authors concluded that consumptions higher than 2 cups of coffee per day increased the risk of antihypertensive drug treatment [RRs (95% CI) for consumption of 2-3, 4-5, 6-7, and ≥8 cups of coffee/day were 1.29 (1.09-1.54), 1.26 (1.06-1.49), 1.24 (1.04-1.48) and 1.14 (0.94-1.37) as compared with 0-1 cups/day)]. Finally, Uiterwaal et al., 32
found that women abstainers and heavy consumers (>6 cups of coffee per day) had lower risk of hypertension than moderate consumers (1 to 3 cups/d). Most of these studies suggest that although caffeine intake acutely increases blood pressure, 33
regular exposure to caffeine can attenuate this effect. In addition, a study found that consumption of 3 cups of coffee per day increased the risk of stroke among hypertensive patients 11
(RR=2.1, 95% CI: 1.2-3.7). This study pointed to caffeine as potentially responsible for this association by increasing cardiovascular resistance and decreasing cerebral blood flow, which impair the already damaged vascular system in these patients. 34
In our study, an inverse association between coffee consumption and risk of stroke was only apparent in women without hypertension, but no increase in risk of stroke was seen among hypertensive participants. More research is necessary to elucidate whether coffee may have a detrimental effect on these patients.
We also examined the effect of coffee on stroke separately in women with and without diabetes mellitus. Long-term studies have consistently found an association between higher coffee consumption and lower risk for type 2 diabetes. 17
One study has assessed the effect of coffee on fatal stroke among diabetic patients, finding no association even with consumptions as high as 7 cups/day. 10
Similarly, in our study, we did not find association between coffee and stroke in the subsample of diabetic patients. Although coffee has been shown to have a beneficial effect on glucose metabolism, 17
the null association between coffee and stroke found in these patients may reflect the important effect of diabetes on atherosclerosis and hypercoagulability, among other vascular alterations, 35
which neutralizes any beneficial effect of coffee in this population.
Hypercholesterolemia is another important risk factor for stroke. Although short-term clinical trials have confirmed the cholesterol-raising effect of diterpenes present in boiled coffee, 15
no long-term studies have assessed this association. In a previous cross-sectional study, 1
we did not find increased levels of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol among individuals consuming non-paper filtered coffee compared to non consumers. In the present study, we found an inverse association between coffee and stroke among participants without hypercholesterolemia but not among those with the risk factor. We can only speculate that the effect of coffee might be of a lower relevance for patients with a higher degree of atheromatosis.
Lastly, smoking is a strong confounder in the study association because it is a potent risk factor for stroke and because smoking is more frequent among coffee drinkers. Therefore, stratified analyses were performed to more thoroughly eliminate residual confounding. Coffee consumption was associated with a substantially lower risk of stroke among non-smokers, but not among current smokers. We hypothesize that the potential benefit of coffee reducing the risk of stroke cannot counterbalance the detrimental effect of smoking on health.
Several mechanisms might help to explain the reduced incidence of stroke that we observed among individuals who consumed coffee. Some substances in coffee may have beneficial effects on glucose metabolism, inflammation and endothelial dysfunction. For example, habitual coffee consumption has been associated with higher insulin sensitivity. 36
In addition, we previously reported an inverse association of caffeinated coffee consumption with surface leukocyte adhesion molecules (E-selectin) and with C-reactive protein (CRP), an inflammatory marker in diabetic women, as well as an inverse association of decaffeinated coffee consumption with CRP in healthy women. 37
Furthermore, the phenolic compounds of coffee (chlorogenic acid, ferulic acid, and p-coumaric acid) have strong antioxidant capacity. 38
The modest inverse association between decaffeinated coffee consumption and risk of stroke in our study supports the hypothesis that components in coffee other than caffeine may be responsible for the potential beneficial effect of coffee on stroke risk.
The present study had several strengths for the examination of the association between coffee consumption and risk of stroke. First, the study included multiple repeated measures of coffee consumption limiting misclassification of coffee consumption. Some measurement error in the assessment of coffee consumption may still have occurred because data on consumption was self-reported. However, results from our validation study indicate that coffee was among the most accurately reported foods in the dietary questionnaire. 19
Second, we were able to control for potential confounders in more detail than in earlier studies, because information on risk factors has been updated every 2 years; however, residual confounding by other factors associated with coffee consumption cannot be excluded. Third, data collection on incident strokes was thorough and a high percentage of events were confirmed by imaging studies. The possibility that reverse causation may have biased our results should be considered. For example, women who were diagnosed with hypertension may have lowered their consumption of caffeinated coffee as a result of the diagnosis. We addressed this issue by examining the association between coffee and risk of stroke among non-hypertensive women only, as well as performing additional analyses that stopped updating consumption when hypertension was diagnosed. The associations between coffee and risk of stroke were similar to those in the main analysis.
In conclusion, in this long-term follow-up study, coffee consumption was not associated with an increased risk of stroke. In contrast, we observed that women who regularly consumed coffee had a modestly lower risk of stroke than non-consumers. Our data support the hypothesis that components in coffee other than caffeine may lower risk of stroke, although the association was modest and the biological mechanism is unclear. These results should be supported by further research before considering the possible implications for public health and clinical practice.