CR (BMI) influences salt mortality risk?

[Guest guest]

Hi All,

How does our weight acting as a proxy for our CR affect our

susceptibility to the effects of sodium on our blood pressure?

It seems that we might even benefit from higher sodium

level, if we are to believe the trend of decreasing in normal

compared with a higher rate for those who are overweight for the

risk of sodium and all-cause mortality in the below paper

that is pdf-available and for which the Table 4 at the end

of this post may be used for those of us who like to look at

what, at least I, consider to be the bottom line:

all-cause mortality.

Also for the data in the table, does the (not significant) 25%

greater cardiovascular than all-cause mortaltiy risk indicate that

the difference is due to less risk of cancer in CRers?

See also in this regard the post in our archives from

Rae in the below.

The paper central to this post is taken from Lancet.

For the Medline abstract of this Lancet paper, see:

http://tinyurl.com/64zax

Regarding the issue of salt risk for mortality, the issue has been

discussed previouly, and the current paper states:

" a high sodium

intake could have some direct effects on cardiovascular risk

not mediated by blood pressure. Our findings lend support

to this hypothesis. "

For the previous discussion from Rae, see:

>>>>>>>>>>>>>>

-----Original Message-----

From: The CR Society, a group of people practicing Calorie

Restriction for

health purposes. [mailto:CRSOCIETY@...] On

Behalf

Of Rae

Sent: Friday, November 19, 2004 11:23 PM

CRSOCIETY@...

Subject: Re: [CR] tech: Hypertension with a grain of salt

... If you look in the Archives you can find plenty of reviews

showing that

Na boosts BP in pretty much everybody; it's just a matter of degree.

And

one doesn't have to develop full-blow hypertension to be at increased

risk of heart disease: the relationship appears to be more or less

continuous. See, recently, (1).

IAC, the cardiotoxic mechanisms of excess Na extend beyond its effects

on BP:

http://lists.calorierestriction.org/cgi-bin/wa?

A2=ind0311 & L=crsociety & P=R59091

>>>>>>>>>>>>>>>>>>>>

[Apparently the above URL site's information boils down to a

hypothetical link to

reactive oxygen species for blood sodium level.]

Now, note the lack of effect of salt for those who are not

overweight

is seen in the below.

First, there were these comments and their reply for the Lancet

paper.

Comments and reply in: Lancet. 2001 Aug 25;358(9282):665-666.

H Alderman, Hillel W Cohen

Lancet. 2001 Aug 25;358(9282):665-6.

Sir—Jaakko Tuomilehto and col-leagues'

data1 help to refine under-standing

of the relation between

sodium intake and human health.

Doubtless most Americans who are not

obese (70%) will draw renewed

comfort from the finding that at least

half of the Finns studied (at or below

median body-mass index) did not seem

to be harmed by the consumption of as

much as 300 mmol sodium in 24 h.

By the same token, consistent with a

previous US finding,2 a higher sodium

intake among obese Finns was

associated with increased cardio-vascular

and all-cause mortality. The

average sodium intake in that study,

however, was much higher than that of

the average US individual.3

These data add further coherence to

the salt story. First, this prospective

observational study supports the

expected heterogeneity in the relation

of sodium intake to health outcomes,

here by the simple expedient of

stratification by weight. Second, these

data lend further credence to the

notion that, for at least half the

population, sodium intake is not

associated with health outcomes.

Indeed, among normal-weight Finns

there was no evidence of harm. Studies

designed specifically to address the salt-health

issue will doubtless add further

precision to our understanding of how

the richness of human genetic,

behavioural, and environmental

diversity affect the complex relation of

sodium and health.4,5

Meanwhile, Tuomilehto and

colleagues add to the evidence of

heterogeneity in the association of

sodium intake with human health. A

reasoned scientific interpretation of

that evidence does not support any

single universal recommendation on

dietary sodium.

1 Tuomilehto J, Jousilahti P, Rastenyte D,

et al. Urinary sodium excretion and

cardiovascular mortality in Finland: a

prospective study. Lancet 2001; 357:

848–51.

2 He J, Ogden LG, Vupputuri S, Bazzano LA,

Loria C, Whelton PK. Dietary sodium

intake and subsequent risk of cardiovascular

disease in overweight adults. JAMA 1999;

282: 2027–34.

3 Intersalt ative Research Group.

Intersalt: an international study of

electrolyte excretion and blood pressure—

results for 24 hour urinary sodium and

Sodium excretion and

cardiovascular mortality

A McCarron

Sir—Jaakko Tuomilehto and col-leagues

(March 17, p 848)1 report that

increases in sodium intake parallel

increases in risk of cardiovascular

events in obese men.

Although they correct for several

important confounding factors in

their analysis, concurrent potassium

excretion was not one of them. The

researchers state that potassium

excretion was measured, but they do

not include it in the report or analysis.

This omission is surprising, and raises

some questions about the implications

of these data.

Other studies have reported that

inadequate dietary potassium increases

cardiovascular risk2 and that there is an

inverse relation between salt and

potassium intake.3 As published,

Tuomilehto and colleagues' analysis is

incomplete; a revised analysis should

acknowledge these established effects

and include adjustment for potassium

excretion. The association they note

between very high salt intake and

increased cardiovascular events

probably represents the long-standing

association between poor diet and

higher cardiovascular risk.

1 Tuomilehto J, Jousilahti P, Rastenyte D,

et al. Urinary sodium excretion and

cardiovascular mortality in Finland: a

prospective study. Lancet 2001; 357:

848–51.

2 Whelton PK, Je J, Cutler JA, et al. Effects

of oral potassium on blood pressure: meta-analysis

of randomized controlled clinical

trials. JAMA 1997; 277: 1624–32.

3 Kant AK, Schatzkin A, Graubard BI,

Schairer C. A prospective study of diet

quality and mortality in women. JAMA

2000; 283: 2109–15.

H Alderman, Hillel W Cohen

Sir—Jaakko Tuomilehto and col-leagues'

data1 help to refine under-standing

of the relation between

sodium intake and human health.

Doubtless most Americans who are not

obese (70%) will draw renewed

comfort from the finding that at least

half of the Finns studied (at or below

median body-mass index) did not seem

to be harmed by the consumption of as

much as 300 mmol sodium in 24 h.

By the same token, consistent with a

previous US finding,2 a higher sodium

intake among obese Finns was

associated with increased cardio-vascular

and all-cause mortality. The

average sodium intake in that study,

however, was much higher than that of

the average US individual.3

These data add further coherence to

the salt story. First, this prospective

observational study supports the

expected heterogeneity in the relation

of sodium intake to health outcomes,

here by the simple expedient of

stratification by weight. Second, these

data lend further credence to the

notion that, for at least half the

population, sodium intake is not

associated with health outcomes.

Indeed, among normal-weight Finns

there was no evidence of harm. Studies

designed specifically to address the salt-health

issue will doubtless add further

precision to our understanding of how

the richness of human genetic,

behavioural, and environmental

diversity affect the complex relation of

sodium and health.4,5

Meanwhile, Tuomilehto and

colleagues add to the evidence of

heterogeneity in the association of

sodium intake with human health. A

reasoned scientific interpretation of

that evidence does not support any

single universal recommendation on

dietary sodium.

1 Tuomilehto J, Jousilahti P, Rastenyte D,

et al. Urinary sodium excretion and

cardiovascular mortality in Finland: a

prospective study. Lancet 2001; 357:

848–51.

2 He J, Ogden LG, Vupputuri S, Bazzano LA,

Loria C, Whelton PK. Dietary sodium

intake and subsequent risk of cardiovascular

disease in overweight adults. JAMA 1999;

282: 2027–34.

3 Intersalt ative Research Group.

Intersalt: an international study of

electrolyte excretion and blood pressure—

results for 24 hour urinary sodium and

potassium excretion. BMJ 1988; 297:

319–28.

4 Tunstall-Pedoe H, Woodward M,

Tavendale R, A'Brook R, McCluskey MK.

Comparison of the prediction by 27

different factors of coronary heart disease

and death in men and women of the

ish heart health study: cohort study.

BMJ 1997; 315: 722–29.

5 Alderman MH. Salt, blood pressure and

human health. Hypertension 2000; 36:

890–93.

Authors' reply

Jaakko Tuomilehto, Pekka Jousilahti,

Antti Tanskanen, Piro Pietinen,

Aulikki Nissinen

Sir—We measured the 24 h urinary

potassium excretion, although we did

not report it. The correlation between

potassium and sodium intake is,

however, direct, not inverse as claimed

by McCarron; in our study the

simple correlation coefficient between

them was 0.41 in men and 0.45 in

women. The sodium-potassium ratio

nevertheless increased with increasing

sodium intake in men from 1.8 to 3.4,

and in women from 1.6 to 3.0 from

the lowest to the highest sodium

intake quartile. The average potassium

intake in Finland is very high.1 In our

cohort it was 90 mmol per 24 h in

men and 74 mmol per 24 h in women.

When we included potassium

instead of sodium in the models, the

associations between events and

potassium excretion were all non-significant

already in the univariate

analysis, as shown in the table. An

increment of one quartile in the 24 h

urinary sodium-potassium ratio was

significantly associated with all-cause

mortality in men but not in women. In

men, the univariate hazard ratio was

1.19 (95% CI 1.02–1.39) and, after

adjustment for other risk factors, was

1.16 (95% CI 1.00–1.36). The

sodium-potassium ratio had no

significant association with any other

study outcome. Finally, when we

included potassium in multivariate

models with sodium simultaneously,

the hazard ratios for sodium were

virtually unaltered.

Given the comments by Alderman

and Cohen, we agree that the average

sodium intake is higher in Finland

than that reported from the USA,1 so

is cardiovascular disease mortality and

average blood pressure.2,3 We reported

the relative risks for 100 mmol per

24 h increments in sodium intake,

similarly to the US study;4 thus the

results are independent of the absolute

level of sodium intake and fully

comparable between studies. Our

results cannot exclude the possibility

that cardiovascular mortality was

almost doubled in non-obese men

(hazard ratio 1.23, upper 95%

confidence limit 1.98).

The correct interpretation of our

results is that high sodium intake

increases the cardiovascular risk in

general and especially in obese people

whose sodium intake is higher than

that in leaner people.5 Overweight

people have many risks, and they

should pay attention to many lifestyle

factors, one of them being salt intake.

We have now shown that high sodium

intake increases the risk of car-diovascular

disease in the Finnish

population. Other risk factors such as

serum cholesterol, blood pressure,

and hyperglycaemia raise the car-diovascular

risk in all populations.

There is no reason to believe that the

risk associated with high sodium

intake would be different in different

populations.

1 Tuomilehto J, Pietinen P, Uusitalo U,

Korhonen HJ, Nissinen A. Changes in

sodium and potassium intake in Finland

during the 1980's. In: Yamori Y,

Strasser T, eds. New horizons in

preventing cardiovascular diseases.

Amsterdam: Science Publishers BV, 1989:

229–40.

2 Kuulasmaa K, Tunstall-Pedoe H,

Dobson A, for the WHO MONICA

Project. Estimation of contribution of

changes in classic risk factors to trends in

coronary-event rates across the WHO

MONICA Project populations. Lancet

2000; 355: 675–87.

3 Wolf HK, Tuomilehto J, Kuulasmaa K,

et al, for WHO MONICA. Blood pressure

levels in the 41 populations of the WHO

MONICA project. J Hum Hypertens 1997;

12: 733–42.

4 He J, Ogden JG, Vupputuri S, Bazzano LA,

Loria C, Whelton PK. Dietary sodium

intake and subsequent risk of

cardiovascular disease in overweight adults.

JAMA 1999; 282: 2027–34.

5 Tuomilehto J, Puska P, Nissinen A, et al.

Community based prevention of

hypertension in North Karelia, Finland.

Ann Clin Res 1984; 16 (suppl 43):

12–21.

Table

Incident & #----Hazard ratio----# patients

Men

CHD 98 1.00 (0.99–1.01) (n=1145)

Stroke 43 0.99 (0.97–1.95) (n=1161)

Women

CHD 30 1.00 (0.98–1.02) (n=1257)

Stroke 41 1.01 (0.99–1.02) (n=1259)

CHD=coronary heart disease.

Coronary heart disease and stroke

incidence for 100 mmol/L increase in

24 h urinary potassium excretion

And, now, here is the paper in question's abstract, followed by

a discussion of Table 4 data and then Table 4.

Lancet. 2001 Mar 17;357(9259):848-51.

Urinary sodium excretion and cardiovascular mortality in Finland: a

prospective

study.

Tuomilehto J, Jousilahti P, Rastenyte D, Moltchanov V, Tanskanen A,

Pietinen P,

Nissinen A.

... We prospectively followed 1173 Finnish men and 1263 women aged

25-64

years ... proportional hazards model.

FINDINGS: The hazards ratios for coronary heart disease,

cardiovascular disease,

and all-cause mortality, associated with a 100 mmol increase in 24 h

urinary

sodium excretion, were 1.51 (95% CI 1.14-2.00), 1.45 (1.14-1.84), and

1.26

(1.06-1.50), respectively, in both men and women. The frequency of

acute

coronary events, but not acute stroke events, rose significantly with

increasing

sodium excretion. When analyses were done separately for each sex,

the risk

ratios were significant in men only. There was a significant

interaction between

sodium excretion and body mass index for cardiovascular and total

mortality;

sodium predicted mortality in men who were overweight. Correction for

the

regression dilution bias increased the hazards ratios markedly.

INTERPRETATION:

High sodium intake predicted mortality and risk of coronary heart

disease,

independent of other cardiovascular risk factors, including blood

pressure.

These results provide direct evidence of the harmful effects of high

salt intake

in the adult population.

PMID: 11265954 [PubMed - indexed for MEDLINE]

... A positive relation between body mass index and obesity

with urinary sodium excretion and blood pressure has been

consistently reported in many epidemiological studies and

clinical trials. Results of some studies have suggested that

people who are overweight are more sensitive to the effect

of sodium on blood pressure than people of normal

weight.26,27 Body mass index and sodium could act

independently on blood pressure28 and a high sodium

intake could have some direct effects on cardiovascular risk

not mediated by blood pressure. Our findings lend support

to this hypothesis.

... 26 Altschul AM, Ayers WR, Grommet JK, Slotkoff L. Salt

sensitivity in

experimental animals and man. Int J Obes 1981; 5 (suppl 1): 27–38.

27 Rocchini AP, Key J, Bondie D, et al. The effect of weight loss on

the

sensitivity of blood pressure to sodium in obese adolescents.

N Engl J Med 1989; 321: 590–85.

28 Dyer AR, Elliott P, Shipley M, Stamler R, Stamler J. Relation of

body

mass index to associations of sodium and potassium with blood

pressure: the INTERSALT Study. Hypertension 1994; 23:

729–36.

29 Engelman K. Sodium intake and mortality. Lancet 1998; 351:

1508–09.

... Table 4: Adjusted hazards ratios of cardiovascular and all-

cause

mortality associated with 24 h urinary sodium excretion

in men of normal weight and in overweight men

Cause of death Hazard ratio (95%CI)*

Normal weight (n=659)

Cardiovascular (n=29) 1.23 (0.76–1.98)

All causes (n=60) 0.98 (0.70–1.36)

Overweight (n=514)

Cardiovascular (n=43) 1.44 (1.02–2.04)

All causes (n=76) 1.56 (1.21–2.00)

*Adjusted for age and study year.

Cheers, Alan Pater