Wednesday, January 22, 2014

Putting "Relative Risk" in perspective - Eades




Jarvik Lipitor AD 36 Absolute risk versus relative risk: Why you need to know the difference



Relative Risk





Absolute Risk



Let’s go back to our Lipitor claim.






Lipitor vs placebo graph Absolute risk versus relative risk: Why you need to know the difference
Control vs Lipitor vs 36percent Absolute risk versus relative risk: Why you need to know the difference


LIpitor vs Control MI Absolute risk versus relative risk: Why you need to know the difference




Control vs Lipitor vs Fatal MI Absolute risk versus relative risk: Why you need to know the difference
Not a huge absolute risk.






CAC 0 vs CAC 1 100 vs MI Absolute risk versus relative risk: Why you need to know the difference
CAC 100 300 vs CAC300 vs MI Absolute risk versus relative risk: Why you need to know the differenceFigure 4. Relative and absolute risks for various CAC scores.  Zero upper left. 1-100 CAC upper right.



Read the complete article here.

20140721 Added this link to good video on relative risk. Well worth the watch.

Friday, January 17, 2014

Ascorbic Acid to Coronary Artery Calcium

Relation of Ascorbic Acid to Coronary Artery Calcium

The Coronary Artery Risk Development in Young Adults Study


Ascorbic acid is an antioxidant nutrient possibly related to the development of atherosclerosis. To examine the relation between ascorbic acid and coronary artery calcium, an indicator of subclinical coronary disease, the authors analyzed data from 2,637 African-American and White men and women aged 18–30 years at baseline who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1985–2001). Participants completed diet histories at enrollment and year 7, and plasma ascorbic acid levels were obtained at year 10. Coronary artery computed tomography was performed at year 15. The authors calculated odds ratios in four biologically relevant plasma ascorbic acid categories, adjusting for possible confounding variables. When compared with men with high plasma ascorbic acid levels, men with low levels to marginally low levels had an increased prevalence of coronary artery calcium (multivariate odds ratio = 2.68, 95% confidence interval: 1.31, 5.48). Among women, the association was attenuated and nonsignificant (multivariate odds ratio = 1.50, 95% confidence interval: 0.58, 3.85). Ascorbic acid intakes from diet alone and diet plus supplements were not associated with coronary artery calcium. Low to marginally low plasma ascorbic acid levels were associated with a higher prevalence of coronary artery calcium among men but not among women.


Overall, our study produced mixed findings. The main positive finding was that low to marginally low plasma ascorbic acid levels (measured at year 10) were associated with an approximately threefold higher prevalence of coronary artery calcium (ascertained at year 15) among men independently of other cardiovascular disease risk factors, including smoking. We did not, however, observe a similar relation among women, perhaps because fewer women had coronary artery calcium, thereby limiting our statistical power to detect such an association. We also cannot exclude the possibility that our findings resulted from chance or residual confounding. The findings among men concur with findings from cross-sectional and longitudinal analyses of participants in the Second National Health and Nutrition Examination Survey (NHANES II) (7, 15). Simon et al. (15) reported previously that NHANES II participants with low to marginally low serum ascorbic acid levels had an increased prevalence of self-reported coronary heart disease. In the NHANES II Mortality Study, which followed participants for a mean of 14 years, Simon et al. (7) found a trend toward increased cardiovascular disease mortality among individuals with low to marginally low serum ascorbic acid levels. Similar to our current findings, those from the NHANES II Mortality Study did not reflect a relation between dietary intake of ascorbic acid and cardiovascular disease endpoints (7).
Our current findings are also consistent with results from some observational studies that also reported low blood ascorbic acid levels to be a risk factor for coronary heart disease (35, 8, 16, 17). Not all observational studies have reported such an association (6, 18), and the few randomized trials examining the effect of vitamin C supplementation on coronary heart disease endpoints, typically in combination with other antioxidants, have produced inconsistent results, ranging from decreased risk to no effect to increased risk (1922). Specifically determining whether marginal vitamin C deficiency is a factor in the development of atherosclerotic coronary disease would be of considerable public health importance, since blood levels consistent with marginal deficiency are prevalent in the population (7) and readily modifiable.
Conclusions based on our findings are qualified by limitations in the study design. We collected information on plasma levels of ascorbic acid 5 years before the coronary artery calcium measurement, but we do not have coronary artery calcium scores before year 15. Therefore, we cannot be certain that differences in plasma ascorbic acid preceded the development of coronary artery calcium since we cannot exclude the possibility that subclinical coronary disease lowered plasma ascorbic acid levels. The concern about the direction of causality is underscored in part because we were unable to find an association between dietary ascorbic acid intake (measured at baseline and year 7) and coronary artery calcium; that is, since blood levels of ascorbic acid are generally correlated with intake, a similar association between lower ascorbic acid intakes and coronary artery calcium would have been expected.
There are several potential explanations for these findings. Because the dietary assessments were performed at baseline and year 7 and plasma ascorbic acid levels were assayed at year 10, we cannot exclude the possibility that dietary and supplement use changed during the intervening period, although we did find a weak, albeit statistically significant, correlation between dietary ascorbic acid intake and plasma ascorbic acid levels (r = 0.14; p < 0.0001). It is also possible that the dietary assessments were not sufficiently accurate or precise to permit the detection of the association. Prospective studies that examined dietary intake of ascorbic acid as a predictor of cardiovascular disease have produced contradictory results. An analysis of data from the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study found that individuals with the highest intakes of ascorbic acid had 25–50 percent lower cardiovascular disease mortality (23). Dietary ascorbic acid intake was also associated with a lower risk of coronary heart disease death among Finnish women (24) and a group of 747 noninstitutionalized elderly Massachusetts residents (25). The Nurses’ Health Study (26), the Health Professionals Follow-up Study (27), and others (28, 29), however, found no significant association between ascorbic acid intake and risk of coronary heart disease.
Ascorbic acid may reduce the risk of cardiovascular disease by a number of mechanisms. Antioxidant status has been hypothesized to be an important factor in atherogenesis, and ascorbic acid is a highly effective water-soluble antioxidant capable of inhibiting lipid peroxidation (30, 31). In some studies, ascorbic acid blood levels and dietary intake have been associated with increased levels of high density lipoprotein cholesterol and decreased levels of total cholesterol (1, 32, 33). The inverse relation between plasma ascorbic acid levels and coronary artery calcium that we observed, however, was independent of cholesterol levels. Ascorbic acid promotes endothelial prostacyclin production (34), improves endothelium-dependent vasodilation (2), and is essential for vascular collagen formation, all factors that may be associated with cardiovascular disease risk. Despite the potential for ascorbic acid to lower the risk for cardiovascular disease, recent clinical trials using antioxidant cocktails that contain ascorbic acid have failed to lower cardiovascular disease risk (1922). We are unaware, however, of clinical trials using ascorbic acid supplementation specifically among individuals with low to marginally low blood levels, our postulated high-risk group.
In addition to the limitations discussed, we were also limited by having only a single measurement of plasma ascorbic acid, which may not reflect long-term plasma concentrations optimally. However, plasma ascorbic acid levels reflect at least the previous several months of dietary intake, even during periods of seasonal variation (35), and are strongly correlated with leukocyte ascorbic acid levels, an indicator of tissue ascorbic acid levels (36, 37). We cannot exclude the possibility that our findings were affected by residual confounding (especially from smoking) or that plasma ascorbic acid levels were simply a healthy diet or lifestyle marker. The association of low plasma ascorbic acid levels with higher prevalence of coronary artery calcium among men was, however, independent of the effects of other lifestyle-related variables, such as education and exercise.
In conclusion, we found that low to marginally low plasma ascorbic acid levels were independently associated with a higher prevalence of coronary artery calcium in young adult men but not in young adult women. Because we cannot exclude chance or residual confounding as an explanation of our findings, our results need to be confirmed by other investigators.


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Monday, January 13, 2014

Does Wheat Cause Coronary Heart Disease?

Does Wheat Cause Coronary Heart Disease?



Conventional Wisdom on Wheat

Most health organizations currently view wheat as a safe food except for people having celiac disease - affecting up to 1% of the population - and people having non-celiac gluten sensitivity. Also whole wheat - as part of whole-grains - is considered to be one of the healthiest food. In fact a diet rich in whole-grains is considered to be protective against CHD.

Why? Because observational studies consistently find that whole-grain consumption is associated with a decreased risk of CHD. Do these results contradict wheat consumption causing CHD?

Are Whole-Grains Protective Against CHD?

According to this study:
Whole-grain intake consistently has been associated with improved cardiovascular disease outcomes, but also with healthy lifestyles, in large observational studies. Intervention studies that assess the effects of whole-grains on biomarkers for CHD have mixed results.
Indeed many studies show that whole-grain consumption is associated with a decreased risk of CHD. But these studies are observational and can only show correlation but not causation.

In fact there is an health-conscious population bias in these studies: for example people consuming the most whole-grains also exercise more and smoke less:
Whole-grain intake and lifestyles



A proof that this health-conscious bias could explain the seemingly protective effect of whole-grains can be found in randomized controlled studies: many of them fail to find any beneficial effect of whole-grains compared to refined grains.

So according to these randomized controlled studies whole-grains are neutral toward CHD risks. How then can we say that wheat causes CHD?

Are All Grains Created Equal?


Here are some results of these studies:
  • wheat increased BMI compared to flaxseed in a 12 months study
  • ApoA to ApoB ratio (a risk predictor similar in efficiency to ApoB alone - here the higher the better) was increased by 4.7% for oat bran and 3.9% for rice bran compared to wheat bran in a 4 weeks study

That could help explaining why people eating more whole-grains are healthier in observational studies since it looks like that they eat more grains like rice and oat and less typically wheat-made food like white bread, pasta and doughnuts:
Whole-grain intake and different grain intakeData from Andersson A. et al., Intakes of whole grains, bran, and germ and the risk of coronary heart disease in men, 2007

Now let’s have a look at studies linking wheat and CHD.

Observational Studies on Wheat

Some observational studies linked wheat and waist circumference gains - waist circumference being a strong predictor of CHD:
  • a study concluded that: ”reducing white bread, but not whole-grain bread consumption, within a Mediterranean-style food pattern setting is associated with lower gains in weight and abdominal fat
  • a Chinese study found that ”vegetable-rich food pattern was associated with higher risk of obesity” but as noted by obesity researcher Stephan Guyenet the association between obesity is in fact stronger with wheat flour than with vegetables
CHD mortality and wheat intake
From Denise Minger
But this is just a single unadjusted correlation and does not prove much. However blogger Denise Minger thoroughly analysed the data of this study and found that the association held strongly after multivariate analysis with any other variable available like latitude, BMI, smoking habits, fish consumption, etc.

Since it is an observational study it cannot prove anything but it is yet another evidence suggesting that wheat consumption causes CHD. Let’s now have a look at randomized controlled trials.

Randomized Controlled Trials on Wheat



The second study is the Diet And Reinfarction Trial (DART). In this 2-year randomized controlled trial, people who already had recovered from an heart attack were split into groups receiving various advices. The main result of this study was that the group advised to eat fatty fish had a reduction in mortality from CHD.

One other advice - the fibre advice - was:

This advice resulted on a 22% death increase:
Total mortality in the fibre advice groupFrom Stephan Guyenet

Since the probability that the fibre advice resulted in a protective or neutral effect was a little too high, this result has been quite overlooked. Had the study last a little longer, it would have raised way more suspicion toward whole-grains.

In fact, researchers found this effect to be statistically significant in a follow-up study. After adjusting for pre-existing conditions and medication use, we can see in the table 4 of this study an hazard ratio of 1.35 (95% CI 1.02, 1.80) for the 2-year period of the randomized controlled trial.

These results are quite telling: according to these researchers, a 2 year randomized controlled trial showed that advising people recovering from an heart attack to eat at least six slices of wholemeal bread per day resulted in a statistically significant 35% percent chance increase of CHD compared to people not receiving this advice.

Wheat, Vitamin D Deficiency And Heart Disease

Many studies found that vitamin D deficiency is associated with CHD.
As this study concludes:


Not the Perfect Culprit



How the wheat is cooked may have a role too. Studies show that sourdough bread improve mineral bioavailability (such as magnesium, iron, and zinc) compared to yeast bread or uncooked whole-wheat. Also content in proteins with potential adverse consequences like gluten or wheat germ agglutinin differs depending of the food type.


There are strong evidences that wheat consumption is a risk factor for CHD. People at risk of CHD should avoid wheat as should those trying to lose weight. In all cases, stopping wheat consumption for a month for example to see how one feel without wheat is always a good idea since there is currently no available method to diagnose non-celiac wheat sensitivities and that even for celiac disease the average delay in diagnostic is 11 years in the US.


Read the complete article here or here.