Another day, another J-curve

From the Mayo clinic:

During a median follow-up of 8.9 years, we documented 8652 incident cases of all-cause death, including 1702 cases of cardiovascular disease death, 4960 cases of cancer death, and 1990 cases of other-cause death. After adjustment confounders and amount of alcohol consumed, higher DHS was significantly associated with a lower risk of all-cause mortality, cardiovascular disease mortality, cancer mortality, or other-cause mortality (Ptrend<.001, Ptrend=.03, Ptrend<.001, and Ptrend<.001, respectively). We observed that the amount of alcohol consumed have different relationships with the risks of all-cause mortality and cause-specific mortality among participants with distinct drinking habits, grouped by DHS. For example, in the joint analyses, a J-shaped association between the amount of alcohol consumed and all-cause mortality was observed in participants with unfavorable DHS (Pquadratic trend=.02) while the association appeared to be U-shaped in participants with favorable DHS (Pquadratic trend=.003), with lower risks in those consuming greater than or equal to 50 g/wk and less than 300 g/wk.

DHS here means a Drinking Habit Score based on whether one drinks with meals and drinking at least 3 times per week. 

So all-source mortality risks are minimised by drinking with meals at least three times per week, with consumption no less than 5 standard drinks per week and no more than 30 standard drinks per week. 

The benchmark I keep in my head, from the older DiCastelnuovo metastudy, is that risks are minimised at about a standard drink a day (a bit less for women, a bit more for men), with risk back up to abstinence-baseline at around 4 standard drinks per day (a bit less for women, a bit more for men). And remember that the "sick quitter" confound is already considered in the DiCastelnuovo work. 

The latest from Mayo is entirely consistent with what we'd expect, for those who pay attention to the literature rather than the prohibitionists. But it's great to see this work continuing to bear up in repeated studies. 

Alcohol, cardiovascular risk, and the NZ Heart Foundation

I'd chided the NZ Heart Foundation for ignoring the cardiovascular benefits of moderate drinking in their heart-health calculator. In comments over at SciBlogs, the Heart Foundation said why:

Heart Foundation says:

07/10/2015 at 8:18 am

Hi Eric,

The reason the Heart Foundation doesn’t include alcohol consumption in its heart age forecast tool is because the relationship between alcohol and cardiovascular disease is so complex. Our general advice is not to consume alcohol as a way of lowering your risk of heart disease. Although the most up to date scientific research suggests there may be some benefits of alcohol for reducing heart disease for some people, this is not the case for everyone, even when consumption is low or moderate. For most people there will be little, or no, overall benefit. Because the research is inconclusive, we don’t include alcohol consumption in our forecast tool.

However, there are many other things with a much stronger evidence base that people can do to reduce their risk of heart disease. These include giving up smoking, eating a healthy diet and exercising regularly. More advice is available here http://www.heartfoundation.org.nz/healthy-living

Kind regards,

Heart Foundation

I'd there replied with a reasonable list of recent articles demonstrating clear cardio benefits of moderate drinking.

Vox this week summarised the literature and reached the same conclusion I did. There are clear cardiovascular benefits from light to moderate drinking. Here's their article and their research summary. I'll note that when they say that there's increased risk after a drink a day, that's increase relative to the point where the health benefits are strongest. If you're looking at all-source mortality risk and comparing to a non-drinking baseline, there remain net health benefits up to about 3-4 standard drinks per day - beyond that, and there's increased risk.

Alcohol and heart attacks

Another finding for the pile: among male heart attack survivors, all source mortality risk for moderate drinkers (1-3 standard drinks per day) was 66% of the risk for non-drinkers. Here's the latest from Pai, Rimm, & Mukamal:

Moderate alcohol consumption of up to two drinks per day was significantly inversely associated with both all-cause and cardiovascular mortality in basic and adjusted models. The multivariable-adjusted HRs for total mortality were 0.78 (95% CI: 0.62–0.97) for 0.1–9.9 g/day, 0.66 (95% CI: 0.51–0.86) for 10.0–29.9 g/day, and 0.87 (95% CI: 0.61–1.25) for ≥30 g/day (P for quadratic trend = 0.006) (Table 2). Similarly, for cardiovascular mortality, the adjusted HRs were 0.74 (95% CI: 0.54–1.02) for 0.1–9.9 g/day, 0.58 (95% CI: 0.39–0.84) for 10.0–29.9 g/day, and 0.98 (95% CI: 0.60–1.60) for ≥30 g/day (P for quadratic trend = 0.003). Additional adjustments for caloric intake, omega-3 fatty acids, ST-elevation and site of initial MI, and creatinine did not appreciably attenuate the risk estimates. Although HRs were similar across alcoholic beverage types, in analyses mutually adjusted for beer, wine, and liquor, there was no significant association between specific beverage type and mortality

Ok, what if the people who were sickest after their heart attacks quit drinking and confound the measure? They also check mortality against pre-MI drinking patterns and find pretty much the same result: the adjusted hazard ratio increases from 0.66 to 0.7.

Our results clearly support the hypothesis that long-term moderate alcohol consumption among individuals with prior MI may be beneficial for all-cause and cardiovascular mortality. This U-shaped association may be stronger among men with better long-term prognosis after MI and further examination is warranted to determine the suitability of moderate alcohol consumption among individuals with other severe cardiovascular conditions.

Wonder if the doctors here note this kind of advice...

Moderate drinking and health - more evidence

From the Sun, Rimm et al paper:

Despite the lack of literature on moderate alcohol use and successful ageing [EC: which their paper provides], our findings are supported by previous observations that moderate alcohol intake is inversely associated with various specific health outcomes that are common among older populations, including coronary heart disease[20], stroke [21], diabetes [22], cognitive decline [18], dementia [23], and physical limitations [24]. In experimental investigations in humans, moderate consumption of alcohol has profound, beneficial effects on multiple pathophysiological processes [2], such as insulin resistance, inflammation, dyslipidemia, endothelial dysfunction, and hemostasis, which play important roles in the etiology of many health conditions. There remains a concern in women that moderate alcohol consumption may increase risk of breast cancer [25],[26]. At the same time, data from the current study on successful ageing and several other total mortality studies [27],[28] that examined midlife alcohol use suggest the benefits of moderate alcohol consumption on overall health might outweigh the risks of specific diseases such as breast cancer. Another potential mechanism that links moderate alcohol consumption to successful ageing is the effects of moderate drinking on psychosocial functioning, which may integrate social, mental, and physical health. For example, studies have documented potential benefits of moderate alcohol use on appetite [29] and social contacts [30], which may improve health for ageing populations, although more studies are needed to explore these psychosocial effects further[31]. The current study also provides novel evidence that, even at moderate intake levels, drinking regularly throughout the week rather than concentrating alcohol intake in just 1 or 2 d may provide greater benefits. This observation was consistent with previous findings that regular rather than episodic alcohol drinking pattern was associated with lower risk of cardiovascular disease and diabetes [32]–[35], although mechanisms behind different drinking patterns remain to be elucidated.

Each of the links above, from the paper, gets you the footnote where you can pull up the cited paper.

Any bets whether the NZ Ministry of Health will update its nutritional guidelines for older people?

Previously on this topic at Offsetting, in chronological order:

• Moderate Drinking and Health
• The J-Curve
• The J-Curve: Science versus Politics
• Saying it again, louder
• Results I don't fully believe
• How do I love the Ministry of Health?
• And MoH responds

This week's nomination

I'm a fan of Auckland's Stats Department's "Bad Stat of the week" contest. I won their inaugural one by nominating John Pagani. I would have won another one but for lack of competition; alas.

Today's entry? Jennie Connor's trashing of a rather nicely conducted study on the health benefits of moderate drinking. Let's start with the study.

Qi Sun and a team including Eric Rimm found that moderate alcohol consumption correlates with good aging and health outcomes in middle-aged nurses in the US: the Nurses' Health Study. They follow a set of over a hundred thousand female registered nurses, starting in 1976 and surveyed every two years subsequently. It was set up to look at the long-term effects of oral contraceptive use but has been used in lots of other studies since.

They averaged reported alcohol intake in the 1980 and 1984 follow-up studies to get a measure of mid-life alcohol consumption, then checked to see whether alcohol consumption at mid-life increased the likelihood of successful aging, defined as being free of major chronic diseases and having no major cognitive or physical impairment and no mental illness.

To avoid the "sick quitter" confound, they dropped from the sample any participants who had:

• Chronic diseases at baseline
• Those diagnosed with alcohol dependence or chronic liver cirrhosis
• Those reporting a significant reduction in alcohol use within 10 years before baseline

So, we shouldn't have former drinkers who quit because of poor health included in the reference group.

Next, they worried about confounding through other health behaviours. They controlled for a wide range of dietary, health, physical activity variables and life history of smoking. When you have observations every two years on a large group of women over a thirty year period, you can do a lot. But, you still can't completely correct for things you can't observe.

What can you do? You can check to see how much of the effect is reduced when you add in all the health behaviours for which you can control. If the effect drops substantially, it's likely there are other things for which you can't control that are correlated with the things for which you can control and might further reduce things. If the effect doesn't move much, it's not likely that other health behaviours are driving things.

Table 2, above, gives the relevant comparisons. Compared to non-drinkers, the odds ratio for those consuming 1.5-3 standard drinks per day was 1.26 in a model adjusting only for age and 1.28 in a model adjusting for all the health and activity correlates. It's exceedingly unlikely that unobserved health behaviours would attenuate the effect if correcting for observed health behaviours accentuates the effect.

They also run things within a cohort restricted to never-smokers. The pattern remains, though statistical significance is lost (you don't get a lot of never-smokers among nurses in a cohort that starts in 1976).

Ok. so what does Connor bang on about then?

The idea that moderate drinking may be good for health is well entrenched, but has been increasingly questioned, including by New Zealand epidemiologists Professors Jennie Connor and Rod Jackson, who challenged the theory in Britain's Lancet journal in 2005.
Professor Connor, of Otago University, told the Science Media Centre the Harvard study added nothing to the many similar studies that were "unreliable for answering questions about the health effects of drinking because of their design".
The supposed health benefit might be due to differences in lifestyle - other than drinking - that were associated with being a low-risk drinker.
"It may be true that women who drink one drink a day are healthier than others, but we do not know if it has anything to do with the alcohol, as these women are not the same as others in a variety of ways."
There was no scientific justification for the promotion of alcohol as health-enhancing for any sub-group of the population.
"The potential for harm is great, and the potential for good is unknown."

What had Connor and Jackson warned about in the Lancet? Two things that Sun, Rimm et al do a pretty good job in ruling out: confounding of never-drinkers with former drinkers, and unobserved health behaviours.

Jennie: if it's unobserved health correlates that are doing the job, why the heck does the relationship get stronger once they corrected for other health behaviours? If some underlying "healthy type" is driving things, that'll correlate with the other health behaviours that we can observe and will reduce the effect of alcohol on successful aging, not increase it. In other specifications, there are small reductions in the odds ratio in the multivariate model as compared to the bivariate one. But the reduction is small, like from 1.43 to 1.35. If throwing in a kitchen sink of health behaviours that are likely to correlate with the unobserved health behaviours reduces the effect by less than twenty percent, it's pretty unlikely that full controls would reduce the odds ratio to 1 or less.

And so I'm nominating Jennie Connor for the bad stat of the week contest for her trashing of what seems a pretty solid study.