Heart longevity and health factors

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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@...

__________________________________

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