The take home is that having chocolate as a continuing component in the diet suppresses heart flutter and arterial fibrilation. The consumption problem is that it is typically mixed with sugar. For the past year, i have been shaking chocalate into my tea and this works well.
Choco originally was consumed with scant sugar and effectively hot sauce in aztec times. So w have a lot to learn regarding the use of choco in foodstuffs.
The data is building up for choco and it is medicaly postive..
Chocolate intake and risk of clinically apparent atrial fibrillation: the Danish Diet, Cancer, and Health Study
Discussion
Conclusions
Key messages
What is already known on this subject?
What might this study add?
How might this impact on clinical practice?
Objective To evaluate the association between chocolate intake and incident clinically apparent atrial fibrillation or flutter (AF).
Methods
The Danish Diet, Cancer, and Health Study is a large population-based
prospective cohort study. The present study is based on 55 502
participants (26 400 men and 29 102 women) aged 50–64 years who had
provided information on chocolate intake at baseline. Incident cases of
AF were ascertained by linkage with nationwide registries.
Results
During a median of 13.5 years there were 3346 cases of AF. Compared
with chocolate intake less than once per month, the rate of AF was lower
for people consuming 1–3 servings/month (hazard ratio (HR) 0.90, 95%
confidence interval (CI) 0.82 to 0.98), 1 serving/week (HR 0.83, 95% CI
0.74 to 0.92), 2–6 servings/week (HR 0.80, 95% CI 0.71 to 0.91) and ≥1
servings/day (HR 0.84, 95% CI 0.65 to 1.09; p-linear trend <0 .0001="" and="" for="" men="" p="" results="" similar="" with="" women.="">
Conclusions
Accumulating evidence indicates that moderate chocolate intake may be
inversely associated with AF risk, although residual confounding cannot
be ruled out.
Atrial
fibrillation (AF) is the most common arrhythmia in clinical practice,
affecting 2.7–6.1 million people in the USA and 8.8 million in the
European Union.1 AF is associated with a higher risk of stroke, heart failure, cognitive decline, dementia and mortality,2 so identifying methods for preventing and identifying effective treatments for AF is of great public health importance.
Moderate
consumption of cocoa and cocoa-containing foods may promote
cardiovascular health due to their high content of flavanols, a subgroup
of polyphenols with vasodilatory, antioxidant and anti-inflammatory
benefits.3 ,4
There has been extensive research showing that moderate consumption of
chocolate, particularly dark chocolate, improves markers of
cardiovascular health5 and is associated with a lower rate of myocardial infarction,6 heart failure,7 ,8 composite cardiovascular adverse outcome and cardiovascular mortality.9 However, there is limited research on whether chocolate intake is associated with a lower rate of AF.
Recent
evidence suggests that the pathophysiology of AF involves an
inflammatory cascade resulting in a release of cytokines, reactive
oxygen species and stimulation of fibroblast proliferation,
differentiation and activation.10
Higher levels of inflammation may result in endothelial damage,
increased platelet activation and increased expression of fibrinogen
that leads to electrical and structural remodelling of atrial tissue and
thereby increase AF risk.11
Therefore, we hypothesised that the anti-inflammatory and antiplatelet
benefits of cocoa may be associated with a lower rate of AF.
We
aimed to evaluate whether there is an association between chocolate
intake and the rate of clinically apparent AF after adjusting for
relevant confounders in a large prospective cohort study of men and
women enrolled in the Danish Diet, Cancer, and Health Study.
Between
December 1993 and May 1997, the prospective Danish Diet, Cancer, and
Health Study invited 160 725 individuals to participate. Inclusion
criteria were 50–64 years of age, residence in the greater Copenhagen or
Aarhus area and no previous cancer diagnosis in the Danish National
Patient Register. At enrolment, anthropometric measurements were taken
and biological materials were collected at one of the study centres;
information on diet and lifestyle was obtained using self-administered
questionnaires including a semiquantitative food frequency questionnaire
(FFQ). Using the unique personal identification number (CPR number), we
linked the cohort to the Danish National Patient Register to identify
primary discharge diagnoses for AF or flutter (International
Classification of Diseases, 10th Revision: I48) through December 2009.
The study was approved by the regional Ethical Committees on Human
Studies (jr.nr. (KF) 11–037/01) and (jr.nr. (KF) 01–045/93) and the
Danish Data Protection Agency. All participants gave verbal and written
informed consent.
At baseline, participants completed a 192-item FFQ that was validated against two 7-day weighed diet records.12 ,13
Average intake of each food item during the last 12 months was reported
in 10 categories from ‘never’ to ‘4–5 per day’. For each participant,
average daily intake was calculated using the Food Calc software V.1.3
(J Lauritsen, University of Copenhagen; http://www.ibt.ku.dk/jesper/foodcalc/).
Standard recipes and sex-specific portion sizes were applied to
calculate intake in grams per day by using data from the 1995 Danish
National Dietary Survey, 24-hour diet recall interviews from 3818 of the
study participants14 and several cookbooks. A serving of chocolate was defined as 1 ounce, consistent with the results of a validation study15
that showed that the approximate serving size of chocolate in Swedish
men is 30 g chocolate. The questionnaire did not differentiate between
milk and dark chocolate, but most chocolate consumed in Denmark has a
minimum of 30% cocoa solids.16
All
citizens of Denmark have a unique personal identification number that
is used in all national registries, and updated information is available
on emigration, hospitalisations and death. The Danish National Patient
Register includes discharge diagnoses from in-hospital patients since
1977 and additional discharge diagnoses from emergency rooms and
outpatient visits since 1995.
The outcome in this study
was incident clinically apparent AF and/or atrial flutter (AFL) during
the study period. Diagnoses were recorded using the Eighth International
Classification of Diseases (ICD-8) until the end of 1993 (AF (427.93)
and AFL (427.94) in the Danish version which is equivalent to AF or AFL
(427.4) in the international version). From January 1994, the ICD-10
classification was used with the diagnosis of AF and/or AFL (I.48). The
validity of the combined diagnosis of AF and/or AFL is high, with a
positive predictive value of 92.6% in this cohort.17
If a patient had both an emergency room visit and a hospital admission
on the same date, only the in-hospital diagnosis was considered in order
to avoid possible misclassification. In line with previous
observational studies, the combined diagnosis of ‘AF and/or AFL’ was
referred to as AF.
We
obtained information on demographics and lifestyle factors using a
self-administered questionnaire. Body mass index (BMI), blood pressure
and total cholesterol were measured by a laboratory technician at the
time of recruitment.18
We used self-reports, ICD codes and Anatomical Therapeutic Chemical
(ATC) drug codes to obtain information on prevalent and incident
hypertension, diabetes mellitus and cardiovascular disease (yes/no).19
Individuals
were considered at risk from the date of the study questionnaire
(1993–1997) until the date of first hospital admission for AF, death,
emigration or end of follow-up (December 2009), whichever came first.
Consistent with prior studies on chocolate intake and AF, we modelled
chocolate intake using the following categories of servings of 1 ounce
bars or packets of chocolate: <1 1="" 2="" 95="" a="" af.="" age="" allowed="" and="" as="" association="" baseline="" between="" by="" calculate="" chocolate="" chose="" class="xref-bibr" confidence="" constructed="" covariates="" cox="" day.="" for="" hazard="" hazards="" href="http://heart.bmj.com/content/103/15/1163?utm_source=facebook&utm_medium=social&utm_campaign=heart&utm_content=heart_q4_chocolate&utm_term=americas#ref-20" id="xref-ref-20-1" intake="" intervals="" models="" month="" multivariable="" of="" priori="" proportional="" rate="" ratio="" s="" scale="" sex="" the="" time="" to="" vary="" we="" week="" with="">20
<1 1="" 2="" 95="" a="" af.="" age="" allowed="" and="" as="" association="" baseline="" between="" by="" calculate="" chocolate="" chose="" class="xref-bibr" confidence="" constructed="" covariates="" cox="" day.="" for="" hazard="" hazards="" href="http://heart.bmj.com/content/103/15/1163?utm_source=facebook&utm_medium=social&utm_campaign=heart&utm_content=heart_q4_chocolate&utm_term=americas#ref-20" intake="" intervals="" models="" month="" multivariable="" of="" priori="" proportional="" rate="" ratio="" s="" scale="" sex="" the="" time="" to="" vary="" we="" week="" with="">
that we considered potential confounders on the basis of their
association with development of AF: from the baseline data we included
information on sex, BMI (kg/m2), systolic blood pressure
(mm Hg), total serum cholesterol (continuous), total calories
(continuous), coffee consumption (continuous), alcohol consumption
(g/day), smoking status (never, former, current) and years of education
beyond elementary school (0,<3 3="">4 years). We used regularly
updated information on hypertension (yes/no), diabetes mellitus (yes/no)
and cardiovascular disease (yes/no) using time-varying covariates.
Because there was no gradient in caffeine across categories of chocolate
intake and it may be a consequence of chocolate intake, we did not
include caffeine consumption as a covariate. We conducted tests of the
linear component of trend for increasing categories of chocolate intake
by assigning the median values for each category and testing the
statistical significance of the term in the multivariable model.
<3 3="">
To
test the robustness of the model, we examined whether the HRs varied by
sex, history of hypertension, diabetes or cardiovascular disease by
conducting likelihood ratio tests to compare models with versus without
cross-product terms for categories of exposure and the potential
modifier. We constructed a multivariable model further adjusted for
caffeine from sources other than chocolate (coffee, tea and soft drinks)
instead of adjusting for coffee consumption. Since unrecognised illness
may influence chocolate consumption at baseline, we conducted a
sensitivity analysis excluding the first 2 years or 5 years of
follow-up.
We tested the proportional hazard assumptions
using Schoenfeld residuals and interactions with the logarithm of time,
and we found no significant violations after allowing the baseline
hazard to vary by sex. Statistical analyses were performed using Stata
V.13 (Stata Corp, College Station, Texas, USA) with two-tailed tests set
at α=0.05 for statistical significance.
Among
the 57 053 women and men recruited, we excluded participants for whom
information was missing on chocolate intake (n=16), inclusion date
(n=42) or one or more confounders (n=477). In addition, we excluded one
participant with no FFQ, 451 participants with a previous record of AF
in the Danish Registry and 564 participants who had a history of cancer
at baseline (the primary outcome of the original cohort study). This
resulted in a sample of 55 502 participants for these analyses. In
total, 3346 incident cases of AF occurred during a median of 13.5 years
of follow-up. Overall, 36% of the sample were current smokers at
baseline. Participants with higher levels of chocolate intake were more
likely to report higher levels of daily caloric intake, a higher
proportion of calories from chocolate and a higher level of educational
attainment (table 1).
Table 1
Baseline characteristics of the subjects in the Danish Diet, Cancer, and Health Study according to frequency of chocolate intake
Compared
with chocolate intake of less than once per month, the rate of AF was
lower for people consuming 1–3 servings/month (HR 0.90, 95% CI 0.82 to
0.98), 1 serving/week (HR 0.83, 95% CI 0.74 to 0.92), 2–6 servings/week
(HR 0.80, 95% CI 0.71 to 0.91) and ≥1 servings/day (HR 0.84, 95% CI 0.65
to 1.09; p-linear trend <0 .0001="" a="" class="xref-fig" href="http://heart.bmj.com/content/103/15/1163?utm_source=facebook&utm_medium=social&utm_campaign=heart&utm_content=heart_q4_chocolate&utm_term=americas#F1" id="xref-fig-1-1">figure 1
).
Figure 1
Multivariable
hazard ratios (HRs) and 95% confidence intervals (CIs) according to
frequency of chocolate intake in the Danish Diet, Cancer, and Health
Study.
p trend is the value for linear component of trend.
Age
was the time scale in the Cox models and we adjusted for total
calories, sex, BMI, systolic blood pressure (mm Hg), total serum
cholesterol (continuous), coffee consumption (continuous), alcohol
consumption (g/day), smoking status (never, former, current), years of
education beyond elementary school (0, <3 3="">4 years),
hypertension (yes/no), diabetes mellitus (yes/no) and cardiovascular
disease (yes/no).
<3 3="">
In
analyses stratified by sex, the incidence rate of AF was lower among
women than men at each level of chocolate intake, but the lower risk of
AF with higher levels of chocolate intake was apparent for both men
(p-linear trend=0.002) and women (p-linear trend=0.017) in the
multivariable models accounting for several potential confounders (figure 1).
Among women, the strongest inverse association was seen for one serving
of chocolate per week (HR 0.79, 95% CI 0.66 to 0.95) and, among men,
the strongest inverse association was seen for 2–6 servings of chocolate
per week (HR 0.77, 95% CI 0.67 to 0.90).
In sensitivity
analyses to test the robustness of the model, the results were similar
across levels of history of hypertension (p-interaction=0.69) and
cardiovascular disease (p-interaction=0.74). Although the results were
different for the 284 individuals with diabetes (p-interaction=0.01),
this was driven by the small number of individuals with diabetes who
reported high levels of chocolate intake. The results were almost
identical when we adjusted for caffeine from sources other than
chocolate (coffee, tea and soft drinks) instead of adjusting for coffee
consumption.
The results were not meaningfully altered
in analyses excluding the first 2 or 5 years of follow-up, suggesting
that the results are not likely to be due to the potential impact of
reverse causation.
In
the Danish Diet, Cancer, and Health Study, higher levels of chocolate
intake were associated with an 11–20% lower rate of clinically apparent
AF among men and women. We adjusted for total caloric intake since, a
priori, we anticipated that it would be associated with the risk of AF
and may confound the association. Since chocolate only contributes a
small proportion of total calories, the results of the model do not
imply that higher levels of chocolate intake results in substantially
lower intake of other foods.
Two prior prospective
cohort studies examined the association between chocolate intake and the
rate of AF. Our results are consistent with results from the Women's
Health Study which reported that moderate chocolate intake was
associated with a 1–14% lower rate of self-reported AF, although the
estimates for each category of intake did not reach statistical
significance.21
Conversely, results from the Physicians' Health Study of men did not
find evidence of an association between chocolate intake and
self-reported AF, and the point estimates suggested that higher levels
of chocolate intake may be associated with a 4–14% higher rate of
self-reported AF, although the results did not reach statistical
significance.22 In the current study, the lower rate of AF with higher levels of chocolate intake was apparent for both men and women.
There
are several potential sources of heterogeneity across the studies. In
this study we identified cases of clinically apparent AF as a primary
cause in the National Registry whereas the prior two studies assessed
the risk of self-reported AF verified in medical records. Based on the
two prior studies, it may appear that the association varies by sex, but
the results were similar for men and women enrolled in the Danish Diet,
Cancer, and Health Study. It is possible that the accuracy of
self-reported chocolate intake or AF symptoms was different for the
sample of women recruited from the general population in the Women's
Health Study compared with reporting by the physicians enrolled in the
Physicians' Health Study, but it is unclear how this would result in a
systematic bias. It is also possible that the presence of potential
confounding by factors related to chocolate intake and AF risk is
different for the two samples, but this too is not clear or verifiable
from the available data. Since chocolate in Europe has a higher cocoa
content than chocolate in the USA,16
it is possible that our results were stronger than the results of the
two US studies due to higher intake of potentially protective components
of chocolate per serving.
Recent evidence suggests that
an inflammatory cascade resulting in leucocyte activation may lead to
generation of reactive oxygen species, proliferation of fibroblasts and
adverse turnover in matrix proteins. This may result in electrical and
structural atrial remodelling and lead to the incidence of AF. The
antioxidant, anti-inflammatory and antiplatelet properties of cocoa may
improve endothelial function, lipid levels, blood pressure and insulin
resistance23 and decrease fibrosis and downstream electrical and structural remodelling of atrial tissue.10 ,11
In addition, a typical 100 calorie serving of dark chocolate contains
36 mg of magnesium, which has hypotensive and antiarrhythmic effects.24 These properties may explain the lower cardiovascular risk associated with moderate chocolate intake.
The
higher flavonoid content of dark chocolate compared with milk chocolate
may yield greater cardiovascular benefits. A randomised trial found
that, compared with milk chocolate, dark chocolate may have a higher
caloric content but it also promotes greater satiety and lowers the
desire to eat something sweet, resulting in an overall lower caloric
intake.25
In addition, flavanol content and total antioxidant capacity in plasma
may be lower if cocoa is consumed with milk or if cocoa is ingested as
milk chocolate.26
Furthermore, cocoa is usually consumed in high calorie products that
use fat and sugar, and modern manufacturing of chocolate may result in
losses of more than 80% of the original flavonoids from the cocoa beans.27
Therefore, it may be advantageous to find ways to consume cocoa in
forms other than chocolate bars. The ongoing Cocoa Supplement and
Multivitamin Outcomes Study is a large randomised trial testing the
effect of a concentrated cocoa extract on cardiovascular risk, and may
provide insight on the efficacy and feasibility of ingesting cocoa in
this form.
There are some limitations to our study that warrant
discussion. Although we had extensive data on diet, lifestyle and
comorbidities, we cannot preclude the possibility of residual or
unmeasured confounding. For instance, data were not available on renal
disease and sleep apnoea. However, after adjusting for age, smoking
status and other potential confounders, the association was somewhat
attenuated but remained statistically significant. We did not have
information on the type of chocolate or cocoa concentration. However,
most of the chocolate consumed in Denmark is milk chocolate. In the
European Union, milk chocolate must contain a minimum of 30% cocoa
solids and dark chocolate must contain a minimum of 43% cocoa solids;
the corresponding proportions in the USA are 10% and 35%.16
Despite the fact that most of the chocolate consumed in our sample
probably contained relatively low concentrations of the potentially
protective ingredients, we still observed a robust statistically
significant association, suggesting that our findings may underestimate
the protective effects of dark chocolate.
As with any
study using self-reported exposure information, there is a concern of
poor recall. However, our FFQ was validated in a study comparing two
7-day weighted diet records.13
Furthermore, if the misclassification of chocolate intake was unrelated
to AF incidence, our results would likely be an underestimate of the
protective effect of chocolate. We have no information on how changes in
chocolate consumption may have affected a participant's risk of AF.
Chocolate intake and covariate data were only available at baseline and,
for most participants, in the fifth year of follow-up and may have
changed over the 13.5 years of follow-up, resulting in some
non-differential misclassification of exposure which would reduce the
power to detect an association. In addition, this study was limited to
cases with a diagnosis of AF as a primary cause. We did not have
information on cases of silent AF, elective DC cardioversions or AF
reported in outpatient clinics and emergency room visits. Therefore, it
is likely that we substantially underestimated the overall incidence of
AF in the population. However, the restriction to diagnosed incident AF
cases should not affect the validity of the current study since the
identification of diagnosed symptomatic AF is unlikely to be impacted by
levels of habitual chocolate intake. Finally, this study and the prior
studies identified in our systematic review were primarily composed of
Caucasian participants, and the results may not be generalisable to
other populations if the association is modified by genetic factors.
Despite
these limitations, our study has many strengths including a large
sample size, a prospective population-based design, detailed data on
diet and factors potentially related to exposure and outcome, and almost
complete follow-up of the study cohort over many years.
Participants
with higher levels of chocolate intake had a lower rate of clinically
apparent incident AF or flutter. Future research is necessary to confirm
this finding and to determine whether high levels of chocolate intake
are associated with higher AF risk.
- Several studies have reported cardiovascular benefits of chocolate intake, but only two studies with discrepant findings have examined the association between chocolate intake and risk of atrial fibrillation (AF).
- In this large prospective cohort study we found that, compared with individuals reporting chocolate intake less than once per month, the rate of AF was lower for people consuming chocolate regularly, with similar results for men and women.
- Chocolate intake may be inversely associated with AF risk. Therefore, dark chocolate may be a healthy snack option that helps to prevent the development of AF.
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