Re: Heart longevity and health factors

November 9, 2005

Hi folks:

This study Al posted may be even more interesting for what the

authors did not definitively say, but which their data clearly

indicate. Take these two paragraphs:

" Measurements: Risk factors were classified at routine examinations

performed between the ages of 40 and 50. Stepwise sex-adjusted

logistic regression models predicting the outcomes of survival and

survival free of morbidity to age 85 were selected from the following

risk factors: systolic and diastolic blood pressure, total serum

cholesterol, glucose intolerance, cigarette smoking, education, body

mass index, physical activity index, pulse pressure, antihypertensive

medication, and electrocardiographic left ventricular hypertrophy.

Results: More than one-third of the study sample survived to age 85,

and 22% of the original study sample survived free of morbidity.

Lower midlife blood pressure and total cholesterol levels, absence of

glucose intolerance, nonsmoking status, higher educational

attainment, and female sex predicted overall and morbidity-free

survival. The predicted probability of survival to age 85 fell in the

presence of accumulating risk factors: 37% for men with no risk

factors to 2% with all five risk factors and 65% for women with no

risk factors to 14% with all five risk factors. "

Then extract the REALLY interesting parts:

They studied the relationship between 'survival and healthy survival

to age 85' and TEN risk factors. To the surprise of no one here they

found that high BP, high total cholesterol, glucose intolerance,

smoking, low educational attainment (all measured in mid-life), and

of course not being female, each resulted in lower survival. Nice to

have this information confirmed, certainly. But not what one would

classify as being novel information. Right?

***BUT*** what I do find REALLY interesting in that study is that

among the ten supposed risk factors studied fully half were NOT

associated with better survival.

And what were the factors that were **NOT** associated with better

survival? ....................

BMI

PHYSICAL ACTIVITY

PULSE PRESSURE

ANTIHYPERTENSIVE MEDICATION

ELECTROCARDIOGRAPHIC LEFT VENTRICULAR HYPERTROPHY

chuckle, chuckle ..................

Rodney.

--- In , Al Pater <old542000@y...>

wrote:

>

> Hi All,

>

> Many here are middle-aged CRers. How do our heart disease risk

factors, such as

> those in PMID: 15096581, predict our living longer and healthier?

This question

> seems to have been addressed in a new paper.

>

> See the pdf-available paper below. Two observations from the

figures are in []s in

> the below experpts.

>

> Terry DF, Pencina MJ, Vasan RS, Murabito JM, Wolf PA, MK,

Levy D, D'Agostino

> RB, EJ.

> Cardiovascular risk factors predictive for survival and morbidity-

free survival in

> the oldest-old framingham heart study participants.

> J Am Geriatr Soc. 2005 Nov;53(11):1944-50.

> PMID: 16274376

>

> Objectives: To examine whether midlife cardiovascular risk factors

predict survival

> and survival free of major comorbidities to the age of 85.

>

> Design: Prospective community-based cohort study.

>

> Setting: Framingham Heart Study, Massachusetts.

>

> Participants: Two thousand five hundred thirty-one individuals

(1,422 women) who

> attended at least two examinations between the ages of 40 and 50.

>

> Measurements: Risk factors were classified at routine examinations

performed between

> the ages of 40 and 50. Stepwise sex-adjusted logistic regression

models predicting

> the outcomes of survival and survival free of morbidity to age 85

were selected from

> the following risk factors: systolic and diastolic blood pressure,

total serum

> cholesterol, glucose intolerance, cigarette smoking, education,

body mass index,

> physical activity index, pulse pressure, antihypertensive

medication, and

> electrocardiographic left ventricular hypertrophy.

>

> Results: More than one-third of the study sample survived to age

85, and 22% of the

> original study sample survived free of morbidity. Lower midlife

blood pressure and

> total cholesterol levels, absence of glucose intolerance,

nonsmoking status, higher

> educational attainment, and female sex predicted overall and

morbidity-free

> survival. The predicted probability of survival to age 85 fell in

the presence of

> accumulating risk factors: 37% for men with no risk factors to 2%

with all five risk

> factors and 65% for women with no risk factors to 14% with all five

risk factors.

>

> Conclusion: Lower levels of key cardiovascular risk factors in

middle age predicted

> overall survival and major morbidity-free survival to age 85.

Recognizing and

> modifying these factors may delay, if not prevent, age-related

morbidity and

> mortality.

>

> ... Framingham Heart Study (FHS) ... A prior study from the FHS

reported on risk

> factors measured in middle age that were associated with survival

to the age of 75.6

> Although it is helpful to understand the relationships between

these risk factors

> and average longevity, the prior work did not answer the question

about which

> antecedent risk factors predict survival in the oldest old,

commonly defined as age

> 85 and older.7 Nor did it evaluate factors influencing morbidity-

free survival to

> age 85. Other prospective examinations of risk factors for

survival, such as those

> done by the Cardiovascular Health Study8 and the Honolulu Heart

Study,9 have focused

> on importance of risk factors at an older age rather than at middle

age. In contrast

> to the aforementioned studies, the current study examined the

effect of favorable

> middle-age risk factors on survival to very old age. Furthermore,

it was sought to

> understand factors associated with living in good health, as well

as factors

> associated with survival per se. ...

>

> ... RESULTS

>

> Table 1 includes baseline characteristics of the participants

between the ages of 40

> and 50, classified by whether they survived to age 85. More than

one-third (35.7%)

> of the study sample survived to age 85, as shown in Figure 1, with

more women

> (44.7%) surviving than men (24.1%).

>

> Table 1. Baseline Characteristics of Those Who Did and Did Not

Survive to Age 85

> ==================================

> Characteristic Nonsurvivors n = 1,628 Survivors n = 903

> ==================================

> Female, n (%)* 786 (48) 636 (70)

> Systolic blood pressure, mmHg, mean±SD* 132±17 125±14

> Diastolic blood pressure, mmHg, mean±SD* 84±10 80±8

> Total serum cholesterol, mg/dL, mean±SD* 236±39 229±36

> Glucose intolerant, n (%)* 60 (4) 8(1)

> Cigarette smoker, n (%)* 1,149 (71) 458 (51)

> Education, n (%)*

> <High school graduate 645 (40) 268(30)

> High school graduate 519 (32) 312 (34)

> >High school 464 (28) 323 (36)

> Body mass index, kg/m2, mean±SD 25.8±4.1 25.0±3.5

> Alcohol, ounces/wk, mean±SD 20±31 13±22

> Physical Activity Index, mean±SD 33±6 32±5

> Pulse pressure, mmHg, mean±SD 47±10 45±8

> Antihypertensive usage, n (%) 117 (7) 33 (4)

> Left ventricular hypertrophy, n (%) 17 (1) 0 (0)

> ==================================

> *These seven covariates were retained in the most parsimonious

models. Subsequent

> covariates were not retained in the model.

> Information on alcohol intake was available on 1,623

nonsurvivors and 903

> survivors. It was not included in the logistic regression model,

because it was not

> collected at all baseline examinations.

> Physical activity index (description in methods section) was

available on 1,465

> nonsurvivors and 822 survivors.

> SD = standard deviation.

>

> Of all eligible participants at baseline, 22% (542/2,475; the

denominator did not

> include the 56 individuals who were lost to follow-up) survived to

age 85 free of

> the morbidities examined. Of those who survived to age 85, 60%

(542/903) survived

> without any of the morbidities examined. Stepwise logistic

regression was used to

> determine risk predictors for survival to age 85 and survival free

of major

> morbidity (Table 2). Individuals were considered to have achieved

healthy aging if

> they did not die or develop myocardial infarction, coronary

insufficiency,

> congestive heart failure, stroke, cancer (excluding nonmelanoma

skin cancer), or

> moderate or severe dementia before age 85. The most parsimonious

model retained sex

> and five risk factors: blood pressure, total serum cholesterol,

glucose intolerance,

> history of smoking, and education (Table 2). For the models

predicting survival,

> systolic blood pressure was selected; for the models predicting

survival free of

> major morbidity, diastolic blood pressure was selected. Tests for

effect

> modification by sex for the factors retained in the most

parsimonious model were not

> statistically significant. In secondary analysis, birth cohort did

not enter the

> most parsimonious model.

>

> Table 2. Multivariate-Adjusted Odds Ratios (OR) and Confidence

Intervals (CIs) for

> Risk Factors Related to Survival and Survival Free of Major

Morbidity to Age 85 and

> Older

> ==================================

> Risk Factor Survival to Age 85 (n = 903)---Survival to Age 85----

Free of Major

> Comorbidity* (n = 542)

> ----OR (95% CI) P-value----OR (95%

CI) P-value

> ==================================

> Female 2.00 (1.66–2.41) <.001 2.08 (1.66–2.61) <.001

> Systolic blood pressure (per 20 mmHg) 0.57 (0.50–0.64) <.001 — — —

> Diastolic blood pressure (per 10 mmHg) — — — 0.64 (0.57–0.72) <.001

> Serum cholesterol (per 40 mg/dL) 0.89 (0.79–0.96) .005 0.82 (0.76–

0.92) .001

> Glucose intolerance (present vs absent) 0.30 (0.14–0.64) .002 0.13

(0.03–0.54) .005

> Smoking history (present vs absent) 0.47 (0.39–0.57) <.001 0.51

(0.41–0.63) <.001

> Education (one category increase) 1.25 (1.12–1.39) <.001 1.20 (1.06–

1.35) .004

> ==================================

> Note: Risk factors considered in stepwise models were sex,

systolic blood

> pressure, diastolic blood pressure, pulse pressure,

antihypertensive medication

> usage, total serum cholesterol, body mass index, glucose

intolerance,

> electrocardiographic left ventricular hypertrophy, smoking,

education, and physical

> activity index. For covariate definitions, see Methods.

> *Comorbidities were myocardial infarction, coronary

insufficiency, congestive

> heart failure, stroke, cancer, and dementia.

>

> None of the individuals with a diagnosis of definite diabetes

mellitus or

> electrocardiographic left ventricular hypertrophy between the ages

of 40 and 50

> survived to age 85. Because of the small number affected, there was

a lack of power

> to demonstrate a significant relationship between diabetes mellitus

or left

> ventricular hypertrophy and mortality by age 85. Hence, glucose

intolerance, which

> was a significant predictor of mortality, was examined. The

presence of glucose

> intolerance significantly decreased the odds of survival to age 85

to 0.30 and the

> odds of survival to age 85 without major comorbidity to 0.13.

>

> In addition to glucose intolerance, other factors were

significantly related to

> survival and major comorbidity–free survival. Being female doubled

the odds of

> surviving to age 85 and surviving free of major comorbidity. Having

high systolic

> blood pressure decreased the odds of survival to age 85 to 0.57,

and having high

> diastolic blood pressure decreased the odds of survival to age 85

free of major

> comorbidity to 0.64. Having elevated serum cholesterol decreased

the odds of

> survival to age 85 to 0.89 and of major comorbidity–free survival

to 0.82.

> Similarly, the presence of smoking history decreased the odds of

survival to age 85

> to 0.47 and major comorbidity–free survival to 0.51. One category

increase in

> education increased the odds of survival to age 85 to 1.25 and of

major

> comorbidity–free survival to 1.20. A C-statistic of 0.71

characterized the model's

> discrimination ability.

>

> Estimated probabilities of survival to age 85 were examined by

evaluating individual

> risk factors (Figure 2) that were retained in the most parsimonious

model. Each risk

> factor was examined separately at lower and higher levels; all of

the other risk

> factor values were modeled at their mean level. Lower levels of

each risk factor

> were associated with a higher probability of survival to age 85.

For example,

> nonsmokers had a 45% probability of surviving to age 85, whereas

the survival

> probability for smokers was 28%.

>

> [The Figure 2 risk ratios for low versus high were: glucose

intolerance, 2.5;

> systolic blood pressure, 1.9; smoking, 1.5; education, 1.3; and

cholesterol, 1.15.]

>

> Sex-specific accumulated risks from multiple risk factors are

demonstrated in Figure

> 3. The first bar of the figure demonstrates the probability of

survival to age 85

> for individuals with no risk factors, whereas each successive bar

demonstrates the

> probability of survival to age 85 in the presence of an increasing

number of risk

> factors. The predicted probability of survival to age 85 fell in

the presence of

> accumulating risk factors: 37% for men with no risk factors to 2%

with four or more

> risk factors and 65% for women with no risk factors to 14% with

four or more risk

> factors.

>

> [The risk differential in Figure 3 for sex remained about the same

for 0, 1, 2 and

> 3, until the last four or more risk factors category.]

>

> DISCUSSION

>

> In the FHS original cohort, lower levels of cardiovascular risk

factors in middle

> age, including blood pressure (systolic for survival to age 85 and

diastolic for

> survival free of major morbidity), serum cholesterol, lack of

glucose intolerance,

> and the absence of cigarette smoking, predicted survival, as well

as major

> morbidity-free survival, to age 85. In addition, female sex and

higher educational

> attainment predicted survival to age 85 and survival free of major

morbidity.

> Furthermore, the predicted probability of survival to age 85 fell

dramatically in

> the presence of an increasing number of these risk factors measured

during middle

> age: 37% for men with no risk factors to 2% with four or more risk

factors and 65%

> for women with no risk factors to 14% with four or more risk

factors.

>

> Other large long-term cohort studies have demonstrated the

importance of individual

> risk factors in young adulthood and midlife in relation to long-

term mortality.2022

> For example, one examined cardiovascular and noncardiovascular

mortality 16 to 22

> years after an initial assessment of risk factors in five large low-

risk cohorts of

> young adult and middle-age men and women from the Multiple Risk

Factor Intervention

> Trial and the Chicago Heart Association Detection Project in

Industry and reported

> that those with low risk-factor profiles (total cholesterol <200

mg/dL; blood

> pressure <120/80; and absence of smoking, diabetes mellitus, and

myocardial

> infarction) had significantly lower coronary heart disease and

cardiovascular

> disease death rates than those at higher risk.23 The current study

extended this

> knowledge by examining survival to very old age and by including

education, an

> indicator of socioeconomic status, as a candidate risk factor.

Moreover, the current

> study differed by examining not only survival but also morbidity-

free survival.

>

> Of those who survived to age 85, 60% (542/903) survived without

major morbidity from

> the age-related diseases that were examined. The results are

consistent with other

> studies that indicate that individuals who survive to older ages

often do so in good

> health, avoiding frailty and morbidity.24,25

>

> The factors predicting survival to age 85 and older identified in

this study are

> congruent with the factors cited by the 2002 World Health

Organization (WHO) report

> as major contributors to the global burden of disease in the

developed world.26 In

> addition to the cardiovascular risk factors noted above, the WHO

report noted that

> elevated body mass index, low intake of fruits and vegetables, and

lack of physical

> activity increased burden of disease.26 According to the WHO's

Comparative Risk

> Assessment Collaborating Group, hypertension, hypercholesterolemia,

elevated body

> mass index, low intake of fruits and vegetables, lack of physical

activity, and

> smoking contribute to 13.5%, 12.9%, 10%, 6%, 5.6%, and 23.6%,

respectively, of

> deaths in developed nations. The WHO also noted that these factors

contribute

> significantly to loss of healthy life as measured using disability-

adjusted life

> years.27

>

> Other studies have demonstrated that socioeconomic status is an

independent risk

> factor for all-cause28 and cardiovascular-disease mortality.29,30

To assess this

> risk, education was included in the model as a proxy for

socioeconomic status, and

> it was demonstrated that it was an independent predictor of

longevity and

> morbidity-free longevity. In models not including educational

attainment, lower body

> mass index was predictive of survival and major morbidity–free

survival to age 85

> (data not shown). Other factors that it was not possible to assess,

such as health

> behaviors and access to healthcare, may also affect survival and

the development of

> age-related disease.

>

> Fortunately, all of the middle-age cardiovascular risk factors in

this model

> predicting survival and major morbidity–free survival to age 85 are

modifiable. For

> example, antihypertensive medications have been demonstrated not

only to reduce

> elevated blood pressure but also to improve cardiovascular

prognosis.31 Lifestyle

> interventions in high-risk subjects have been shown to prevent type

2 diabetes

> mellitus.32 The benefits of lifestyle changes and treatments for

smoking

> cessation,33,34 weight loss,35 and cholesterol reduction36,37 have

been demonstrated

> as well. Modest improvements in these factors could lead to

substantial gains in

> disease-free survival.26,3840

>

> One of the most notable findings was that all of the FHS

participants included in

> the study sample that had definite diabetes mellitus between the

ages of 40 and 50

> died before age 85. The uniform lethality of diabetes mellitus in

this study may be

> in part due to temporal factors such as a lack of therapeutic

options and a lack of

> understanding of the importance of tight glucose control, which

have subsequently

> become the standard of medical care. Nevertheless, in view of the

increasing

> prevalence of obesity41 and its contribution to diabetes mellitus,

hypertension, and

> hypercholesterolemia, these results are troubling. Without a

concerted effort to

> reduce obesity and diabetes mellitus on a population-wide basis,

currently

> lengthening life expectancies may begin to be reversed.

>

> None of the individuals with a diagnosis of electrocardiographic

left ventricular

> hypertrophy between ages 40 and 50 survived to age 85. Analogous to

diabetes

> mellitus, the uniform lethality of left ventricular hypertrophy in

this series may

> be in part due to the less-aggressive approach to the treatment of

blood pressure

> during the earlier part of follow-up. Recent data indicate that the

return to normal

> of left ventricular hypertrophy,42,43 according to

electrocardiogram or

> echocardiogram, is associated with decreased cardiovascular events.

Unfortunately,

> many individuals with hypertension are still not treated

adequately.44

>

> ... Implications

>

> Lower midlife levels of blood pressure, body mass index, serum

cholesterol; absence

> of glucose intolerance; nonsmoking history; female sex; and higher

educational

> attainment predicted survival to age 85 and major morbidity-free

survival in the FHS

> cohort. Prior studies have demonstrated that modifying these risk

factors in middle

> age is cost-effective and beneficial for the disease-free survival

of individuals to

> very old age. These data emphasize the importance of health

promotion in young and

> mid-adulthood to promote healthy aging. ...

>

> Al Pater, PhD; email: old542000@y...

>

> __________________________________

> FareChase: Search multiple travel sites in one click.

> http://farechase.

>

November 9, 2005