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mccoy

Finnish study posted by Al Pater

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Appreciations for Al Pater, who's keeping up with his valuable contribution on relevant literature. I found this article he posted particularly intersting because it outlines  very basic health benchmarks, very simply evaluable. The study has all the limits of an epidemiological analysis. The main governing independently evaluated factors associated to reaching 90 years of life turned out to be:

  1. Smoking
  2. Blood glucose
  3. Serum lipids
  4. BMI

Very simple and basic, maybe obvious and trivial, but a simplification in a world of confusion cannot but be welcome.

Again, the conclusions are seemingly trivial but keeping in mind those 4 references is a very handy set of benchmarks we can contemplate as our starting guidelines.

More parameters are listed which maybe have seemingly lesser influence on 90-years lifespan (and the scanario might change if we evaluate longer lifespans).

Practicing CR-ON of course guarantees an opptimization of the above parameters, in most cases.

Quote

Major cardiovascular disease (CVD) risk factors in midlife and extreme longevity.
Urtamo A, Jyväkorpi SK, Kautiainen H, Pitkälä KH, Strandberg TE.
Aging Clin Exp Res. 2019 Oct 14. doi: 10.1007/s40520-019-01364-7. [Epub ahead of print]
PMID: 31612429
https://sci-hub.tw/http://link.springer.com/10.1007/s40520-019-01364-7
Abstract
BACKGROUND:
The studies on the association of various midlife risk factors with reaching 90 years or more are scarce. We studied this association in a socioeconomically homogenous cohort of businessmen.
METHODS:
The study consists of men (n = 970) from the Helsinki Businessmen Study cohort (born 1919-1928). Five major cardiovascular disease (CVD) risk factors (smoking, BMI, blood pressure, serum lipids, fasting glucose), consumption of alcohol and coffee, self-rated health and self-rated fitness, were assessed in 1974, at an average age of 50 years. The number of major risk factors was tested as a risk burden. The Charlson Comorbidity Index and the RAND-36 (SF-36) Physical and Mental health summary scores were calculated from surveys in year 2000, at age of 73 years. Mortality dates were retrieved through 31 March 2018 from the Population Information System of Finland.
RESULTS:
244 men survived to the age of 90 representing 25.2% of the study cohort. The survivors had less risk factor burden in midlife, and less morbidity and higher physical health summary score in 2000. Of those with five major risk factors only 7% survived up to 90 years, whereas 51% of those without any risk factors reached that age. Single risk factors reducing odds of reaching 90 years were smoking (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.34-0.67), glucose (0.66, 0.49-0.88), BMI (0.63, 0.46-0.86), and cholesterol (0.71, 0.53-0.96).
CONCLUSION:
Lack of five major CVD risk factors in midlife strongly increased odds of reaching 90 years of age and also predicted factors related to successful ageing in late life.
KEYWORDS:
Cardiovascular risk factors; Life-course; Longevity; Nonagenarians; Successful ageing

 

Edited by mccoy

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I question their cholesterol finding.  They assigned a P value of less than 0.001 for a small difference between groups making it to 90 or not of TC averages of 6.13 and 6.47 of a single reading taken in 1974.  TC is a dynamic value that can swing by a far greater amount in a day than their supposed significant difference in response to changes in diet, exercise, sleep, stress, infections, etc.  TC lumps together all types of cholesterol making it scarcely more useful than BMI which lumps together muscle, fat and bone as if they all have the same impact on longevity.  On their following individual risk analysis TC had the weakest confidence interval and P value of the risk factors considered significant.  But I think they are still massively over rating a value of dubious significance.

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Full text here:  https://link.springer.com/article/10.1007%2Fs40520-019-01364-7

Quote

Todd Allen::  They assigned a P value of less than 0.001 for a small difference between groups making it to 90 or not of TC averages of 6.13 and 6.47 of a single reading taken in 1974. 

Pretty high TC levels all around. (Same with BMI.)

6.13 mmol/L ≈   237.05 mg/dL

6.47 mmol/L ≈   250.20 mg/dL

(To Convert From mmol/L to mg/dL,  for TC, HDL, and LDL cholesterol multiply mmol/L by 38.67)

Edited by Sibiriak

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I agree with Todd that TC is not the more significant parameter in assessing serum lipids, although it turned out to be the less significant of the significant values, with a p-value of the logistic regression = 0.027, the <0.001 p-value was referred to the difference between groups. 

In the end, except for the very significant and very obvious smoking factor, we remain with BMI and 1-hour BG.

The average BMI  varied from 25.4 to 26.3 kgm-2 in the two groups 

The average BG varied from 129 to 140 mg/dL in the two groups.

The BMI values do not appear so different, those who did not reach 90 years had a delta BMI of 0.9 in excess of those who reached 90, which qualitatively does not seem so much, can a few kilos make such a difference?

The BG values are probably more qualitatively interesting.

 

 

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13 hours ago, mccoy said:

The average BMI  varied from 25.4 to 26.3 kgm-2 in the two groups 

Two groups of overweight people with borderline high to high cholesterol, according to mainstream risk analysis.

(Btw, there are  a number of studies which show higher cholesterol levels associated with reduced all-cause mortality.)

Edited by Sibiriak

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Yes, unfortunately at the end of the discussion-dissection this study has revealed pretty disappointing. Next one, LOL

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11 hours ago, Sibiriak said:

Btw, there are  a number of studies which show higher cholesterol levels associated with reduced all-cause mortality.

High cholesterol is positively correlated with longevity late in life. I think you'll have trouble finding a study where mid-life high cholesterol is associated with longer lifespan, as the subjects in this study were. But I'll admit I'm not absolutely sure of this. 

--Dean 

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Interesting point, Dean.    First of all,  I didn't refer to "high cholesterol" in that brief remark,  but rather, admittedly vaguely, "higher cholesterol".  And I  certainly wasn't trying to make any kind of definitive statement about  ideal cholesterol levels or initiate a debate on the issue.    I need to pull up the studies I was thinking about,   but here's one quickly. (It's getting late in my time zone, GMT +7.)

Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults (2019)

https://www.nature.com/articles/s41598-018-38461-y
 

Quote

 

Abstract

It is unclear whether associations between total cholesterol (TC) levels and all-cause mortality and the optimal TC ranges for lowest mortality vary by sex and age. 12,815,006 Korean adults underwent routine health examinations during 2001–2004, and were followed until 2013. During follow-up, 694,423 individuals died. U-curve associations were found. In the TC ranges of 50–199 and 200–449 mg/dL, each 39 mg/dL (1 mmol/L) increase in TC was associated with 23% lower (95% CI:23%,24%) and 7% higher (6%,7%) mortality, respectively. In the age groups of 18–34, 35–44, 45–54, 55–64, 65–74, and 75–99 years, each 1 mmol/L higher TC increased mortality by 14%, 13%, 8%, 7%, 6%, and 3%, respectively (P < 0.001 for each age group), for TC ≥ 200 mg/dL, while the corresponding TC changes decreased mortality by 13%, 27%, 34%, 31%, 20%, and 13%, respectively, in the range < 200 mg/dL (P < 0.001 for each age group). TC had U-curve associations with mortality in each age-sex group. TC levels associated with lowest mortality were 210–249 mg/dL, except for men aged 18–34 years (180–219 mg/dL) and women aged 18–34 years (160–199 mg/dL) and 35–44 years (180–219 mg/dL). The inverse associations for TC < 200 mg/dL were stronger than the positive associations in the upper rang

 


 

Quote

 

Discussion

A U-shaped relationship between TC and mortality was observed in each age-sex group. TC levels associated with the lowest mortality were 210–249 mg/dL in both sexes in all age groups, except for the youngest groups of men, aged 18–34 years (180–219 mg/dL), and women aged 18–34 years (160–199 mg/dL) and 35–44 years (180–219 mg/dL). At TC levels of 50–199 and 200–449 mg/dL, each 39 mg/dL (1 mmol/L) increase in TC was associated with 23% lower (95% CI = 23–24%) and 7% higher (6–7%) mortality, respectively. Inverse associations in the lower TC range were strongest at the ages for which the mean TC levels were highest (men aged 45–54 years and women aged 55–64 years), while positive associations in the upper TC range were strongest in the youngest ages (<45 years) in both sexes. Both the inverse associations in the lower TC range and the positive associations in the upper TC range weakened with advancing age beyond the ages with the strongest associations.

Previous cohort studies have reported inconsistent results on the shape of associations between TC and all-cause mortality, including positive linear, inverse, U-curve, and reverse-L-curve (or reverse-J-curve) associations3,8,9,10,11,13,14,17,22. Some previous studies suggested different shapes of associations by sex and age3,17. The associationbetween TC and mortality was substantially modified by age and, to a lesser degree, by sex, in our study. Our study clearly demonstrated that the shape of association is a U-curve in each sex and each age group, including those aged 75–99 years (mean age: 79.0 years), which constituted 154,321, 80,776, and 18,080 elderly people aged 75–79, 80–84, and ≥85 years, respectively. Considering the weaker effect size associated with high TC with advancing age in the elderly, it is no surprise that previous studies conducted mainly in elderly populations found generally inverse or reverse-L-curve associations13,14. Additionally, the previously reported positive associations in younger adults8, may be explained by the stronger positive associations and lower optimal range in younger ages observed in our study, combined with the higher TC concentrations and larger proportions of morbidity and mortality from heart diseases in Western populations.

The NCEP experts classified TC levels into 3 categories: <200, 200–239, and ≥240 mg/dL, as desirable, borderline high, and high levels, respectively, mainly based on the association between TC and IHD21. In the current study, however, TC levels of 210–249 mg/dL and approximately 200–240 mg/dL were associated with the lowest mortality in the categorical and spline analyses, respectively. Our study suggested that the optimal ranges for overall survival are higher than that those for IHD. Similarly, a higher optimal range for overall survival than for IHD mortality has also been reported for BMI23. In contrast, the optimal ranges for all-cause mortality and IHD mortality were similar for fasting glucose and blood pressure24,25,26,27. Cholesterol levels might be a marker of general health, rather than a marker specific for CVD28. Even within CVD subtypes, TC ranges associated with lowest risk have not been consistent. For example, for stroke, TC levels <200 mg/dL were not associated with the lowest mortality in prospective cohort studies29,30, and randomized trials have not provided clear evidence of whether lipid-lowering therapies, including statins, reduce stroke mortality6,31. Hemorrhagic stroke, respiratory diseases (especially chronic obstructive pulmonary disease), digestive diseases (especially liver disease), and several cancers have been suggested to be associated with lower TC levels10,30,32,33,34; thus, the ranges associated with lowest risk might be even higher for these diseases than those for all-cause mortality. However, we could not examine whether the associations differed by cause of death, due to data unavailability.

Reverse causality has been suggested as an explanation of higher mortality associated with low cholesterol levels. However, a long term follow-up study in a Japanese-American population showed that individuals with low cholesterol levels maintained over a 20-year period had the worst all-cause mortality, and concluded that reverse causality was unlikely to account for the higher mortality associated with low cholesterol entirely14.

Lower optimal ranges for survival at younger ages than at older ages have also been observed for BMI19, whereas consistent ranges have been found regardless of sex and age for blood pressure and fasting glucose26,27,29. Whether different proportions of cause-specific mortality by age lead to the lower optimal range at younger ages needs to be investigated.

The sex- and age- specific levels of TC in the current study of Koreans were lower than those reported in other high-income countries, including Japan, England, and the US15,16,17,35,36. The distribution of TC levels by sex and age, however, were generally similar to those of other regional and ethnic populations, although detailed information is not always available. TC levels peaked at 50–51 years in men and at 56–57 years in women, and after the peak age, the levels decreased more rapidly in men than in women. The crossover point of the mean TC levels between sexes occurred at the age of 50–51 years, exactly at the median age of menopause37. The steep decline in estrogen corresponds well to the sharp increase in TC in women that was observed around the time of menopause in the current study.

Randomized trials have provided evidence that statin therapy may lower the overall mortality risk in persons with increased cardiovascular risk, mostly due to the reduction of mortality from heart disease5,6. The evidence, however, may not be definitive enough to claim that “the lower the cholesterol, the better” for all-cause mortality reduction in the general population with relatively low heart disease risk38.

The current cholesterol guidelines are heavily based on heart disease risk and recommend a TC range of <200 mg/dL as desirable. TC range <200 mg/dL, however, may not be necessarily a sign of good health when other diseases are considered. The diseases associated with lower TC levels and potential mechanisms have not been conclusively identified. Since the inverse associations in lower TC range were stronger than the positive associations in upper TC range, identification of diseases associated with lower TC levels and further understanding of the mechanisms of such associations may help improve health outcomes in the general population. Pending more research for clarification, careful evaluation and management might increase the chance of preventing and diagnosing potentially life-threatening diseases at an earlier stage in adults with low TC levels.  [ETC.]

 

 

Edited by Sibiriak

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I had a look at the Korean study posted by Sibiriak.

First of all, the median TC in men was always lower than the recommended 200 mg/dL threshold:

 

image.png.8b757dc24fa9cdb6562e74788f8881c7.png

 

Strangely, contrary to common knowledge, the whole population set exhibits a U curve with an optimal range above the 200 mg/dL threshold:

image.png.e2838320452c62dcbeb6852ed5bff32f.png

However, the above data have only been age-adjusted.

The adjusted data, though (for many variables), stratified for age,  still exhibit the same pattern:

 

image.png.b05de9eecaa30e538680225a860b534b.png

 

What about uncertainty? Given the very large numerosity, in men it's practically absent, a little larger in women but a very narrow band:

 

image.png.42a9770688f1b67128d18d64a7d0f18c.png

Linear association seems to contradict the above data, with higher TC suggesting slighter higher HR. Also, it is not clear why th eall-dataset HR is lower than zero.

image.png.868b9fd2f46b31368c419cb7b88dd810.png

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The authors are careful to underline some limiting factors in the study:

  • The population is Korean, so the conclusions are not rigorously applicable to other ethnicities
  • All-cause mortality is considered, whereas lipids are usually used as a risk parameter for CVD mortality
  • The data re unadjusted for statins use, although only 10% of the population used such drug

I would also add that the linear analysis is not coherent with the spline analysis, as a matter of fact, the linear analysis would suggest slightly higher mortality for the >200 mg/dL group

 

My takeaway considerations

  • We all know that TC is presently considered a poor indicator of CVD risk, compared to other parameters like LDLp and TGs; this makes the article not too much useful for practical applications
  • The article focusing on all-cause mortality, and not CVD mortality, previous knowledge is not too much contradicted
  • Practical use for our purposes: probably very little, unless another important memento that many parameters are not best when very little, rather an optimum (a U-curve) very often exists.

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