Because high-sensitivity cardiac troponin T hs-cTnT and N-terminal pro—brain natriuretic peptide NT-proBNP are released directly from myocardial tissue, they provide us with a highly specific measure of cardiomyocyte damage in the case of hs-cTnT and myocardial stress in the case of NT-proBNP. Cardiac troponin has been shown in multiple studies to be associated with atherosclerotic CVD outcomes in men and women with and without established cardiovascular disease, including among participants in the Atherosclerosis Risk in Communities ARIC study 8 — NT-proBNP is the stable N-terminal fragment of the prohormone for cardiac B—type natriuretic peptide and has been robustly associated with myocardial mass, hypertrophy and clinical heart failure, as well as atherothrombotic events such as myocardial infarction and stroke 11 , Because cardiac troponin and natriuretic peptides are markers of future cardiovascular risk, as well as being released directly from myocardial tissue in response to injury or stress, these biomarkers offer the opportunity to advance our understanding of the direct effects of alcohol consumption on the myocardium.
Studying dietary intake and heart health
With this backdrop in mind, the article by Lazo et al. Lazo and colleagues studied participants enrolled in the ARIC study, examining in cross-sectional and prospective analyses the quantity of alcohol consumed in relation to such direct markers of subclinical myocardial risk—hs-cTnT and NT-proBNP. In these analyses, baseline alcohol consumption ranging from 2—7 drinks per week was associated with a lower risk of developing an abnormal troponin after 6 years of follow up, a result that was similar in direction and magnitude if not significance over a range of alcohol doses.
As is the case with any well-done study, this work by Lazo and colleagues raises many more questions than it answers. In particular, while regular alcohol consumption is associated with a lower risk of abnormal troponin measurement results and a higher risk of abnormal NT-proBNP results, it is also associated with a lower risk of CVD. These results are in the expected direction for hs-cTnT but not for NT-proBNP, raising the possibility of alternative competing causes of mortality or morbidity. The observed associations at baseline for hs-cTnT are consistent with the results from our own study of more than women but contradict our findings for NT-proBNP Lazo and colleagues had the advantage of a larger sample size, with a broader range of alcohol exposure, which may explain our discrepant results for NT-proBNP.
One potential explanation for their results could be that hypertension—an adverse effect of alcohol consumption—is mediating the progressive increase in NT-proBNP associated with alcohol use, while the findings related to hs-cTnT support myocardial protective effects perhaps through effects on glucose metabolism or atherosclerosis of moderate alcohol consumption, paralleling previous clinical observations 1. These discrepant effects might explain part of the bidirectional risk profiles observed in relation to alcohol consumption to date.
Furthermore, prior studies have suggested that the development of hypertension can be preceded by increases in NT-proBNP 15 , suggesting that preclinical hemodynamic changes could accompany alcohol use, which could affect release of NT-proBNP. Such changes could also indicate subclinical heart failure from excess alcohol use, as the authors postulate. Next steps in this area could be to examine hypertension as a mediator of these relationships, as well as to further link these findings with different clinical subtypes of CVD, such as coronary heart disease, stroke and heart failure.
Determining whether all types of alcohol exert homogenous effects on these biomarkers could also enable delineation of the active component of alcoholic drinks e. Overall, the findings from Lazo and colleagues represent an important step toward a better understanding of the differential effects of alcohol on CVD. They also illustrate the importance of mechanistic biomarker studies in population-based observational studies to interrogate and develop our understanding of the mechanisms behind health-related behaviors.
Studies such as the one from Lazo and colleagues help us understand and improve our broad recommendations for public health and prevention, in addition to moving us closer to precision-health guided approaches to preventing cardiovascular disease in individual patients. Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: a significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; b drafting or revising the article for intellectual content; and c final approval of the published article.
Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Consultant or Advisory Role: B. Everett, Roche Diagnostics; B. Everett, Abbott Diagnostics. Research Funding: B.
Everett, investigator-initiated awards from Roche Diagnostics. Since ancient times, chocolate has long been used as a medicinal remedy [ 14 ] and been proposed in medicine today for preventing various chronic diseases [ 15 , 16 ]. While chocolate has also sometimes been criticized for its saturated fat content, mostly in the form of long-chain stearic acid, chocolate has also been lauded for its antioxidant potential. However, to this date there are no long-term randomized feeding trials of chocolate to assess effects on actual cardiovascular events.
Nevertheless, there have been many short-term trials of cocoa and chocolate examining effects on cardiovascular intermediates, and numerous epidemiology studies of stearic acid and flavonoids exploring associations with cardiovascular outcomes. This systematic review serves to comprehensively evaluate the experimental and epidemiologic evidence of cocoa and chocolate products. Particularly, we focus on the controversial potential benefits of the chocolate components stearic acid and flavonoids; review their overall effects on CVD risk factor intermediates and CVD endpoints; and conduct a meta-analysis of total flavonoid intake and risk of CHD mortality.
We reviewed English-language MEDLINE publications from January through June for experimental, observational, and clinical studies of relations between the exposure search terms of chocolate, stearic acid, flavonoids including flavonols, flavanols, catechins, epicatechins, and procynadins and the outcome search terms of cardiovascular disease coronary heart disease, ischemic heart disease, stroke , cholesterol, blood pressure, platelet, oxidation, and thrombosis. Approximately papers were reviewed.
Based on the relevance, strength, and quality of the design and methods, publications were selected for inclusion. We mainly focused on studies in humans, particularly randomized trials of either parallel or cross-over design, and prospective observational studies. Since no randomized trials have yet assessed chocolate in relation to definitive CVD outcomes, prospective observational studies evaluating chocolate sub-components and the risk of CVD outcomes were weighted equally in the overall evaluation.
12222 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease
For overall objective evaluation, the strength of the evidence was evaluated by the design and quality of individual studies, the consistency of findings across studies, and the biologic plausibility of possible mechanisms. Finally, consistent with methods of the outdated prior analysis [ 17 ], an updated meta-analysis was conducted and relative risks estimates pooled using a random-effects model [ 18 ].
Saturated fat has long been thought to contribute to atherosclerosis, and thus, adverse for CVD risk. However, stearic acid has been suggested to be a non-atherogenic type of dietary saturated fat.
Frontiers | Heart Failure and a Plant-Based Diet. A Case-Report and Literature Review | Nutrition
Stearic acid is a long-chain saturated fatty acid found commonly in meats and dairy products. Thought it is generally considered that saturated fats overall adversely increase the total cholesterol and LDL levels [ 21 — 23 ], early studies have also suggested stearic acid may be non-cholesterolemic [ 21 , 22 ]. This has been confirmed in a series of studies and a meta-analysis of 60 controlled feeding trials which concludes stearic acid neither lowers HDL, nor increases LDL or total cholesterol [ 24 — 28 ]. The most recent trial also shows the effects of stearic acid on lipids is even similar to oleic and linoleic acids [ 29 ].
Emerging studies have begun to explain how stearic acid in chocolate may be cholesterol-neutral. One suggested mechanism is stearic acid's lower absorption, which has been found in several animal and human studies [ 30 — 33 ], though only minimally in others [ 34 , 35 ].
These discrepancies may be attributed to the relative position of stearate on the triglyceride molecule which may affect its relative absorption rate [ 36 , 37 ]. This might also explain the suggestion that stearic acid from plants sources, such as cocoa, may be different from animal derived sources of stearic acid [ 38 ]. Furthermore, some feeding trials found lower absorption of cocoa buttered compared to corn oil [ 39 ], though not in others [ 40 ]. Finally, another strongly supported protective mechanism relate to the relatively high percent desaturation of stearic acid to monosaturated oleic acid [ 35 , 42 — 45 ], a fat considered hypocholesterolemic [ 27 , 46 — 48 ] and protective against coronary heart disease [ 3 , 49 ].
Two other pathways suggested for potential benefit are stearic acid's potential anti-platelet and blood pressure reductions actions. Feeding trials have shown that stearic acid reduces mean platelet volume [ 50 , 51 ], an index of platelet activation.
However, mixed findings have been observed regarding the relationship between stearic acids and factor VIIc coagulation factor, a predictor of fatal CHD [ 52 — 54 ]. Though an early study suggested that stearic acid may increase factor VIIc [ 55 ], no effect on levels of factor VIIc by stearic acid was observed in two other trials [ 56 , 57 ]. Moreover, additional trials have refuted the earlier small study and, in fact, shown that stearic acid lowered the levels of factor VIIc coagulation factor compared to palmitic [ 50 , 58 ] and other saturated fatty acids [ 58 ].
As for the relationship between stearic acid and blood pressure, two feeding trials found stearic acid did not adversely affect systolic blood pressure [ 28 , 59 ]. Furthermore, cross-sectional analysis within the Multiple Risk Factor Intervention Trial even found stearic acid levels may be inversely associated with diastolic blood pressure [ 60 ]. In summary, given the vast majority of studies showing stearic acid has beneficial or neutral effects on blood pressures and clotting parameters, it appears unlikely stearic acid intake would adversely affect CVD risk through these risk factors.
Data indicates stearic acid does not adversely affect established traditional lipid risk factors, with even favorable lowering of serum triglycerides if isocalorically replaced for carbohydrates. However, the observational studies of stearic acid's association with CVD are inconclusive. Table 2 Among retrospective studies, a Japanese case-control study of serum levels reported no association for stenosis [ 61 ], a Norwegian study found lower odds of MI [ 62 ], while a Costa Rican study of dietary intake found higher risk of MI [ 63 ] with higher intake of stearic acid.
However, the results from the Costa Rican study should not be given much weight since retrospective self-report of dietary intakes are notoriously inaccurate and susceptible to reporting bias [ 64 ]. Nevertheless, higher rates of CHD and CAD progression was found in several prospective studies [ 65 — 68 ], while stroke was not increased in another study [ 69 ]. On the other hand, several limitations exist for observational studies of stearic acid. Finally, since there exists high interconversion of stearic acid to unsaturated fatty acids [ 35 , 42 — 45 ], studies involving serum levels of stearic acid do not answer the relevant causal question of dietary intake of stearic acid and risk of disease.
The associations of long-term serum stearic acid levels represent the effects of post-conversion stearic acid levels after a large proportion of the original dietary stearic acid has already been converted away to monounsaturated fat, which is well-established to exert protective effects against CVD [ 3 , 27 , 46 — 49 ]. Thus, relatively little information can be inferred from observational studies of the association of stearic acid and CHD, and no epidemiologic study has, thus far, appropriately and optimally answered the causal question of the association of dietary stearic acid intake and risk of CVD.
However, a sufficient body of strong evidence from short term randomized trials suggests stearic acid components in chocolate may be beneficial for cardiovascular health.
However, further research in this area is warranted. A g bar of milk chocolate contains mg of flavonoid antioxidants, procyanidins and flavanols [ 12 ]. Flavonoids belong to a class of antioxidants called polyphenols from plants [ 72 ]. The basic structure of flavonoids is a C6-C3-C6 backbone with two armomatic rings and varying degrees of hydroxylation differentiating one flavonoid type from another [ 73 ]. Flavonoids can be divided into various subclasses, important of which are flavones, flavonols, flavanones, catechins, anthocyanidins and isoflavones.
Cocoa, is particularly rich in the flavonoids, epicatechin, catechin, and procyanidins polymers of catechins and epicatechins [ 74 ]. Figure 1. Structural skeleton of flavonoids and classification hierarchy of common flavonoids. Various studies have compared the content of the flavanoids in cocoa with other food stuffs quantitatively. Figure 2 shows the comparative content of flavonoids in milk chocolate and dark chocolate versus other high-flavonoid foods. Per serving, dark chocolate contains substantially higher amounts of flavonoids than milk chocolate mg of catechins per 40 g serving compared to mg in white chocolate [ 75 ], and levels of epicatechin in dark chocolate is comparable to red wine and tea [ 75 ].
In addition to dark chocolate having higher flavonoid content, the biologic effects of flavonoids may also be greater in dark chocolate because milk in milk chocolate may inhibit the intestinal absorption of flavanoids [ 76 ].
Finally, chocolate is also abundant in procyanidin flavonoids, comparable with levels in procyanidin-rich apples [ 77 ]. Thus, chocolate is a rich source of flavonoids, particularly catechins, epicatechins and procyanidins. Flavonoid content and antioxidant capacity ORAC of milk chocolate and dark chocolate versus other high flavonoid foods. Antioxidant activity is reported as oxygen radical absorbance capacity ORAC.
Adapted from: Steinberg et al. J Am Diet Assoc Chocolate flavonoids have shown good dose-response bioavailability in humans [ 11 , 78 , 79 ]. There exists several mechanisms of how flavonoids may be protective against CVD; these include: antioxidant, anti-platelet, anti-inflammatory effects, as well as possibly increasing HDL, lowering blood pressure, and improving endothelial function. The body of trials involving chocolate flavonoids is summarized in Table 1.
Central to the pathogenesis of atherosclerosis is the oxidation of low-density lipoprotein LDL. The chemical structure of flavonoids gives the compound free radical scavenging ability, which means flavonoids may have antioxidant effects [ 80 ]. Various studies have confirmed the role of flavanoids as antioxidants in biological systems.