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Cholesterol in older people

Honolulu [1]
Results
Italy [2]
Results
Italy [3]
Results
Predicting cholesterol reduction [4]
Results
Cholesterol predicting functional decline [5]
Results
Statin use in older people [6]
Results
Comment

One of the most frequently asked questions of Bandolier is about cholesterol in the elderly, and the role of statins in older people (over 70s for convenience), and particularly in the oldest old (over 80s). As best Bandolier knows, there is no simple answer, but there have been a number of studies in recent years, all cohort studies.

There is a general link between low serum cholesterol and increased mortality, though cardiovascular disease remains the highest cause of death. Of course, in older people there are many confounding factors, particularly the propensity for increasing numbers of medical conditions, and be taking increasing numbers of drugs. Both factors tend to increase with age, while kidneys, liver, lungs, heart and muscle have reducing efficiency. Older people tend to eat less, as well.

Bandolier has chosen to review briefly six large studies (at least 1,000 people) published in the last four years. The hope is that by pulling some common threads together we have a more integrated view, if still imperfect understanding.

Honolulu [1]

This was part of a large epidemiological study starting in 1965 with 8,000 Japanese/American men born between 1900 and 1919. The study was based on examinations in 1991-1993, with mortality to end 1996. The examination consisted of demographics, function tests, blood tests, and ECG.

Results

There were 3,572 men aged 71-93 years. Mean serum cholesterol fell from 5.0 mmol/L in those aged 71-74, to 4.6 in those older than 85 years. Analysis by quartiles of serum cholesterol showed that age-adjusted mortality was highest in the quartile with the lowest serum cholesterol (Figure 1). Men in the lowest quartile for total cholesterol were more likely to have a history of weight loss and poor physical functioning (Figure 2). Much of the statistical relationship between low cholesterol and increased mortality was lost when risk factors and frailty measures were taken into account, but it remained in men who had low total cholesterol for about 20 years.



Figure 1: Mortality and cholesterol levels







Figure 2: Cholesterol and weight loss or poor physical functioning





Italy [2]

In 1985 3,282 Italians aged 65 years or older were screened, with demographic data, blood samples, and other cardiovascular and respiratory measurements made. Subsequent mortality was assessed annually by monitoring discharge records and death certificates.

Results

There were slightly more women than men, the mean age was 74 years and the mean total cholesterol 5.7 mmol/L. The average BMI was 26, and 61% were classified as overweight. More men smoked, and more women had diabetes diagnosed. Total follow up was 12 years, with 1,599 deaths.

For women, but not men, overall mortality was significantly higher in those with the lowest cholesterol (below 5.1 mmol/L). Both men and women in the lowest quartile of cholesterol (below 5.1 for women and 4.7 for men) had increased mortality compared with participants with higher cholesterol and BMI above 25.

Women and men in the lowest quintile of cholesterol had higher rates of death from cancer or other causes than those in the highest quintile. For men but not women, the highest quintile of cholesterol conferred an increased risk of coronary heart disease death.

Italy [3]

The study population was all patients aged 65 years or older admitted to 35 clinical centres (geriatric and internal medicine wards) in Italy during May-June and September-October 1995 with data on demography, diagnosis, and blood and other analyses.

Results

There were 2,486 patients admitted (53% women), with an average age of 78 years, and average total cholesterol of 4.7 mmol/L. Total cholesterol in men aged over 85 years was 12% lower than average than in those aged 65-69. Total cholesterol in women aged over 85 years was 6% lower than average than in those aged 65-69.

Disability indices were higher in those with lower cholesterol, as was the incidence of low serum albumin and iron, and a BMI below 20 (Figure 3). Low cholesterol was independently associated with a diagnosis of infectious disease, low serum albumin and low BMI. After adjustment for these factors, the likelihood of having low serum cholesterol did not increase with age.



Figure 3: Cholesterol and weight loss or poor physical functioning





Predicting cholesterol reduction [4]

A random sample of people in four medical programmes in the USA recruited 2,800 adults aged 65 years or older, who had a first examination in 1989-1990. Serum cholesterol was measured at visits five and nine years later, and predictors of change sought in a wide range of other demographic and blood measurements.

Results

In the 1,683 men and 1,154 women the average reduction in cholesterol over four years was 0.16 mmol/L. One-third had no change, while 27% of men and 28% of women had reductions of at least 0.5 mmol/L. Larger reductions were seen in people whose starting cholesterol was highest, particularly over 6 mmol/L. Factors associated with greater decline on multivariate analysis were age, male sex, and higher white cell count, serum albumin, and baseline cholesterol.

Cholesterol predicting functional decline [5]

A longitudinal study in a random sample of a Dutch population examined an adult population aged 55 to 85 years with complete data on serum albumin and total cholesterol at baseline. They were asked at baseline and three-year follow up to perform three simple actions: walk three metres, turn around, and walk three metres back; stand up five times from a kitchen chair with arms folded across their chest; and put on and take off a cardigan. Each was timed, and the times scored according to a simple system.

Results

The mean age of 1,064 participants was 68 years. Low serum albumin (below 43 g/L) was found in 24% of women and 22% of men. Low serum cholesterol (below 5.2 mmol/L) was found in 8% of women and 18% of men. A three year decline in functional performance was associated with low cholesterol in women. In men, functional decline was associated with both low cholesterol and low albumin.

Statin use in older people [6]

The geriatric Ontario Longitudinal database linked several healthcare databases with follow up of mortality over time. It includes 1.4 million residents of Ontario who were alive and 66 years or older in 1998. Information was obtained on medicines prescribed in the year before the cohort began.

The cohort comprised those at high risk of future cardiovascular events, with a history of cardiovascular disease or diabetes. Patients with recent history of cancer were excluded. The final cohort was of 396,000 persons A baseline risk index was created using multiple logistic regression models, and stratified at 25%, 50% and 75% percentiles of death. Low, intermediate and high-risk patients were identified.

Results

Two-thirds of patients in the cohort had cardiovascular disease, 18% diabetes, and the remainder had both conditions. Half were women, and the average age was 75 years. Statins were prescribed in 19%.

Patients prescribed statins were younger, more likely to be men, with a prior heart attack, angina, or invasive procedure, and made more visits to a cardiologist. Patients not prescribed statins were more likely to have diabetes, congestive heart failure, stroke, or live in rural areas.

Patients who were older, or at higher baseline risk of dying over the next three years were less likely to have a statin prescribed. Figure 4 show the relationship between observed three-year mortality and statin prescription for the age group 75-80 years. Progressively lower use of statins in patients with higher cardiovascular risk existed across the full spectrum of risk, and across the entire spectrum of age.



Figure 4: Cardiovascular risk, mortality, and statin prescription





Comment

All complicated stuff, and not easy to make into a simple story. But let’s try, anyway, at the risk of oversimplifying.

Average cholesterol levels fall with increasing age, and low cholesterol is associated with increased mortality, particularly cancer and causes of death other than cardiovascular, which remains a major cause of death in older people. Cholesterol loss appears to be greater in those with an initially high level. There appears to be a pattern, that low cholesterol is associated with low weight or BMI, or weight loss, poor physical functioning, infections, and other markers of lower health, like low serum albumin and iron.

There are probably several things going on together. Reduced hepatic synthesis, appetite and food intake are expected with increasing age. Superimposed might be differing patterns of comorbidity, and the propensity of some people to age faster than others, for reasons we understand poorly. Fit 90 year olds are not the same as sick 70 year olds.

Perhaps this helps explain the paradox of treating older people with statins. Older people at very high risk probably have additional health problems, possibly of more immediate importance than future cardiovascular events. Prescribing a statin is likely to be low on the list of priorities, particularly where many drugs are already prescribed.

Many prescribers would welcome more and better advice on how or whether to prescribe statins to older people at high risk. In the meantime high cholesterol in older people is a problem that has to be dealt with. We might also consider low cholesterol and albumin levels as markers of poor health. The difficulty is knowing what the cut-off should be for low. It might be 4.0 mmol/L or below in people not on statins, but lower in those on statins or with previous cardiovascular disease.

References

  1. IJ Schatz et al. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet 2001 358: 351-355.
  2. E Casiglia et al. Total cholesterol and mortality in the elderly. Journal of Internal Medicine 2003 254: 353-362.
  3. S Volpato et al. The inverse association between age and cholesterol levels among older patients: the role of poor health status. Gerontology 2001 47: 35-45.
  4. TA Manolio et al. Predictors of falling cholesterol levels in older adults: the cardiovascular health study. Annals of Epidemiology 2004 14: 325-331.
  5. BW Schalk et al. Lower levels of serum albumin and total cholesterol and future decline in functional performance in older persons: the Longitudinal Aging Study Amsterdam. Age and Aging 2004 33: 266-272.
  6. DT Ko et al. Lipid-lowering therapy with statins in high-risk elderly patients. JAMA 2004 291: 1864-1870.

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