The Journal of Nutrition, Health & Aging

Volume 16, Number 5, 2012

SERUM HIGH-DENSITY LIPOPROTEIN CHOLESTEROL LEVELS CORRELATE

WELL WITH FUNCTIONAL BUT NOT WITH COGNITIVE STATUS
IN 85-YEAR-OLD SUBJECTS
F. FORMIGA1, A. FERRER2, D. CHIVITE2, X. PINTO3, T. BADIA4, G. PADROS5, R. PUJOL1

1. Geriatric Unit, Internal Medicine Service, Hospital Universitari de Bellvitge, IDIBELL, LHospitalet de Llobregat, Barcelona, Spain; 2. Primary Healthcare Centre El Pl CAP-I, Sant
Feliu de Llobregat, Barcelona, Spain; 3. Lipid and Vascular Risk Unit, Internal Medicine Service, Hospital Universitari de Bellvitge, IDIBELL, LHospitalet de Llobregat, Barcelona,
Spain; 4. Centro de Atencin Primaria Martorell Urb, Martorell, Barcelona, Spain; 5. Laboratori Clnic Metropolitana Sud, Atenci Primria, LHospitalet de Llobregat, Barcelona,
Spain. Corresponding author: Francesc Formiga, MD, PhD, Geriatric Unit, Internal Medicine Service, Hospital Universitari de Bellvitge, 08907 LHospitalet de Llobregat, Barcelona,
Spain, E-mail: fformiga@bellvitgehospital.cat, Phone: (+34) 93 260 74 19; Fax: (+34) 93 260 74 20

Abstract: Objectives: We evaluate the association between high-density lipoprotein cholesterol (HDL-C) levels
and physical and cognitive performance indicators in 85-year-old subjects. Design: Prospective cohort study.
Setting: A community-based study. Participants: 321 subjects enrolled in the Octabaix Study. Methods:
Functional status was determined using the Lawton-Brody Index (LI) and the Barthel Index (BI). Cognition was
assessed using the modified Spanish version of the Mini-Mental State Examination (MEC). We also measured
risks related to nutrition and falls, as well as comorbidity and chronic drug prescription. HDL-C serum
concentrations <40 mg/dl for men and <46 mg/dl for women were used as cut-off values to discriminate between
normal and low HDL-C concentrations. Results: The sample consisted of 197 women (61%) and 124 men. Mean
HDL-C levels were 56.5 15 mg/dl, with gender differences being found (59.3 15 mg/dl in women vs. 52.1
13 mg/dl in men; p<0.0001). Sixty-one subjects (19%) had low HDL-C values. HDL-C levels correlated with BI
(r=0.11, p=0.04) and LI (r=0.17, p=0.002) scores, but not with MEC scores (r=0.08, p=0.13). Poor BI and LI
scores, lower MEC scores, a risk of falls and malnutrition, and polypharmacy were all associated with lower
HDL-C values in the bivariate analysis. Multiple logistic regression analysis showed only a significant
association between normal HDL-C serum values and better BI scores (p<0.001, OR 1.02, 95% CI 1.01-1.04).
Conclusions: Individuals with higher levels of HDL-C had better functional and cognitive status, but after
multivariate analysis this relationship only remained significant for functional status.
Key words: High-density-lipoprotein cholesterol, oldest old, physical function, cognitive function.

Background

In recent years a marked reduction in mortality in later life

has been observed. In conjunction with longer life expectancy
this has led to a steady growth of this segment of the population
(the oldest old), although within this group striking interindividual differences in life expectancy remain (1). The
characteristics of this population group therefore need to be
explored further in order to determine the causes of morbidity
and mortality.
One recent report found that the prevalence of
dyslipidaemia, a prevalent cardiovascular risk factor, was not
lower among the oldest old (2). At all events, an important
aspect to consider is that different epidemiological studies have
confirmed that, as in the adult population, low levels of serum
high-density lipoprotein cholesterol (HDL-C) remain a strong
risk factor for cardiovascular disease in the elderly (3, 4).
Moreover, low HDL-C levels have been associated with an
increased risk of stroke in the Leiden cohort (people over 85
years of age) (5), as well as with higher overall mortality in the
elderly population (6, 7). In addition to better life expectancy,
elderly people with relatively high HDL levels have been
reported to be healthier and more vigorous than those whose
HDL levels were consistently low [8]. Furthermore, severe
disability is strongly associated with low HDL-C levels in this
Received May 31, 2011
Accepted for publication July 4, 2011

population group (9).

By contrast, the relationship between HDL-C levels and
cognitive function remains controversial, although there is
increasing evidence that high HDL-C levels are associated with
improved cognition and dementia-free survival (10, 11). For
example, in a preliminary study with a small sample of
nonagenarians living in our area, we reported that one out of
four nonagenarians had low serum HDL-C concentrations, and
that higher levels of HDL-C correlated with better functional
status and the use of fewer chronic prescription drugs (12). In
this study subjects with low HDL-C scores had poor cognitive
functioning (measured by MEC scores), but this relationship
was not maintained in the multivariate analysis.
The aim of the present study was to determine whether there
is an independent association between HDL-C and physical
function and to study a possible association with cognitive
performance in a broad sample of 85-year-old communitydwelling subjects.
Methods

This study derives from the OCTABAIX project, a

prospective, population-based study of 328 communitydwelling subjects born in 1924 (aged 85 at the time of
inclusion) and assigned to seven primary healthcare teams in

449

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HIGH-DENSITY LIPOPROTEIN CHOLESTEROL IN OCTOGENARIANS

the geographical area of Baix Llobregat in Barcelona, Spain.

The participation rate was 67.5% and there were no differences
among respondents in terms of gender. The combined
population served includes approximately 210,000 inhabitants
and the referral hospital is the Hospital Universitari de
Bellvitge.
The sample has been described in more detail elsewhere (13,
14). Subjects were examined at their place of residence by
trained teams (medical doctors and nurses) skilled in
interviewing the elderly. An interview was performed in all
cases in which the individual was able to participate. A geriatric
assessment and socio-demographic data (gender, marital status,
place of residence, education, and living alone) were included
in the interview. Functional, cognitive and nutritional status
were assessed by instruments currently used in geriatric
practice. Gait and the number of falls were also assessed. The
study was approved by the institutional ethics committee and
all patients, or their caregivers in case of those who were
cognitively impaired, gave written informed consent before
enrolment. We assessed all patients and no exclusion criteria,
such as impaired health or cognitive status, were applied. The
present analysis refers to 321 participants, following the
exclusion of seven individuals because of missing values for
the study variables.

Global geriatric assessment

Functional status was measured using the Barthel Index (BI)
(15) for basic activities of daily living (ADL) and the Lawton
Index (16) (LI) for instrumental ADL. The total score of the BI
ranges from 0-100 points (from help needed in all activities to
total independence), while the LI score ranges from 0 (low
function, dependent) to 8 (high function, independent).
Cognitive function was measured by the modified Spanish
version of the Mini-Mental State Examination (MEC) (17): on
this scale the maximum score is 35, and scores of 23 or below
indicate cognitive impairment. The score was corrected by
education level
Nutritional status was assessed using the Mini Nutritional
Assessment (MNA). The MNA score is based on 18 items
covering four component sub-scores: MNA-1 (four items),
anthropometric measurement (08 points); MNA-2 (six items),
global evaluation (09 points); MNA-3 (six items), assessment
of dietary habits (09 points); and MNA-4 (two items),
subjective assessment of self-perceived quality of health and
nutrition (04 points) (18). The score obtained (maximum 30
points) allowed the elderly subjects to be classified into three
categories: 2430, well-nourished; 1723.5, at risk of
malnutrition; and <17, malnourished.
Gait was evaluated using a modified version of the Gait
Rating Scale from the Tinetti Performance-Oriented Mobility
Assessment. Gait consists of nine components: initiation of
gait, step height and length, step symmetry and continuity, path
deviation, trunk stability, walking stance, and turning while
walking (19). Each component was scored as either 1 (normal)

450

or 0 (abnormal), providing a final score which ranged from 0 to

9, with higher scores indicating a better gait performance.
Subjects with higher scores on the Tinetti have more risk of
falls A fall was defined as any incident in which the patient
ends up on the ground or at a lower level against his/her will
(and not due to an intentional movement) (20). Patients and/or
caregivers were asked about any previous falls in the last year.
The Charlson Index was used to measure global comorbidity
(21). The score here ranges from 0 to a theoretical maximum of
33, depending on the presence of certain diseases with assigned
values. Disease prevalence was determined on the basis of a
review of data from general practice records for stroke and
ischemic cardiopathy. Chronic drug prescription was also
recorded using an extensive review of prescriptions according
to data from medical records and confirmed in personal
interview.

Succesful Aging
We defined non-disabled subjects as those with a better
health status (successful age), who, in addition to being noninstitutionalized (social criteria), had scores of 91 or higher on
the BI( subjects with total independency for basic ADL or
minimal dependence) and 24 or higher on the MEC (scores of
23 or below indicate cognitive impairment) (22).

Blood measurements
Blood was collected in tubes without anticoagulant after an
overnight fast (at least 12 h). Each specimen was centrifuged at
1200 g for 10 min at room temperature and stored at 4C until
analysis. Serum HDL-C concentrations were measured by a
direct enzymatic colorimetric method (HDL-C Plus, Roche
Diagnostics, Basel, Switzerland) and were calculated using the
Friedewald equation (23). The inter-assay coefficient of
variation for HDL-C was less than 5.0%. Total cholesterol
(CHOD-PAP, Roche Diagnostics, Basel, Switzerland) and
LDL-C concentrations (GPO-PAP, Roche Diagnostics, Basel,
Switzerland) were also measured by an enzymatic colorimetric
method. All procedures were carried out with a modular system
analyser (Roche Diagnostics, Basel, Switzerland).
Procedure
In order to categorize HDL-C levels as either low or normal
we followed the European guidelines on CVD prevention in
clinical practice, which consider HDL-C serum concentrations
below 40 mg/dl (<1.0 mmol/l) for men and below 46 mg/dl
(<1.2 mmol/l) for women as being markers of increased
cardiovascular risk (24).

Statistical analysis
Data were analysed using SPSS 15.0 statistical software
(SPSS Inc., Chicago, III). P-values less than 0.05 were
considered significant. All data are expressed as means
standard deviations or frequencies (number, %), as required.
HDL-C was examined as a continuous variable for descriptive

The Journal of Nutrition, Health & Aging

Volume 16, Number 5, 2012

JNHA: NUTRITION

and correlation analysis, and also as a categorical variable

(lower or higher according to the chosen cut-off). Normality of
variables was tested by the Kolmogorov-Smirnov test. The
Students T test was used to compare continuous variables,
with a prior Levene test for equality of variances, while either
the chi-square statistic or Fishers exact test was used for the
comparison of categorical or dichotomous variables.
Correlations between variables were calculated using the
Pearson or Spearman coefficient (r), as appropriate. The
variables associated with low HDL-C values were determined
by logistic regression analysis. The variables entered into the
multivariate model were BI, LI, MEC, MNA, Tinetti and the
number of chronically prescribed drugs (all continuous
variables, without categorization strategy), corrected by gender
and educational level.
Results

Three hundred and twenty-one individuals were finally

included, 197 women (61%) and 124 men. With regard to
marital status, 168 (52.3%) were widowed, 20 (6.2%) were
single and 133 (41.4%) were married. One hundred and ten
subjects (34.3%) were illiterate, 151 (47.7%) had attended
primary school, 46 (14.3%) high school, and 14 (4.4%) had a
university degree. Ninety-eight (30.5%) lived alone.

Geriatric assessment
Mean scores on the LI and BI were, respectively, 5.4 2 and
87.7 18. In 194 subjects (60%) the BI was >89. The mean
MEC score was 26.7 6, and was 24 or higher in 233 subjects
(72.6%). Assessing function and cognition together, 159
(49.5%) subjects met the criteria for successful ageing. HDL-C
serum concentrations were slightly higher in the successful
ageing group (57.1 vs. 55.8; p=0.44). Regarding comorbidity,
the mean Charlson Index was 1.4 1.5. The mean number of
chronically prescribed drugs was 6.1 3, with 254 subjects
(79.1%) receiving three or more drugs.
The mean score on the MNA, used to detect the risk of
malnutrition, was 24.5 3. The assessment of gait yielded a
mean score on the Tinetti Gait Scale of 6.6 2.8. The mean
number of falls during the previous year was 0.4 0.9.

Lipid profile
For the whole study population, mean HDL-C levels were
56.5 15 mg/dl, with gender differences being found (59.3
15 mg/dl in women vs. 52.1 13 mg/dl in men; p<0.0001).
Sixty-one subjects (19%) had HDL-C values below the cut-off
value for normality. HDL-C levels were correlated with scores
on the BI (r=0.11, p=0.04) and LI (r=0.17, p=0.002), but not
with MEC scores (r=0.08, p=0.13).
Mean LDL-C values were 114 31 mg/dl, and in 80
(24.9%) subjects this value was equal to or higher than 135
mg/dl. Total serum cholesterol levels for the whole population
was 194 36 mg/dl, and in 63 nonagenarians (19.6%) these
values were equal to or higher than 220 mg/dl.
Table 1 shows the differences between patient groups

according to the predefined cut-off values for HDL-C. Poor BI

and LI scores lower MEC scores, poor MNA scores, a higher
risk of falling, and more polypharmacy were all associated with
lower HDL values in the bivariate analysis. Multiple stepwise
logistic regression analysis (table 2) showed a significant
association between normal baseline HDL-C serum values and
better ADL performance, as indicated by higher BI values
(p<0.001, OR 1.02, 95% CI 1.01-1.04).
Table 1
Differences between 85-year-old subjects according to serum
HDL-C levels. HDL-C serum concentrations below 40 mg/dl
for men and below 46 mg/dl for women were considered the
cut-off values to discriminate between low and normal HDL-C.
Values are expressed as the number (percentage) or mean
(standard deviation)

Gender
Female
Male
Marital status
Widow
Married
Single
Educational level
Illiterate
Primary school
High school
Degree
Barthel index
Barthel index >90
Spanish Mini-Mental State
Spanish Mini-Mental State >23
Successful ageing
Lawton-Brody index
Charlson Index
Chronically prescribed drugs
Nutritional assessment questionnaire
Living alone
Tinetti Gait Scale
Falls previous year
Stroke
Ischemic cardiopathy
Total cholesterol, mg/dl
LDL cholesterol, mg/dl

Low HDL
(n=61)

Normal HDL
(n=260)

27 (44.3%)
31 (50.8%)
3 (4.9%)

141 (54.2%)
102 (39.2%)
17 (6.5%)

0.25

39 (63.9%)
22 (36.1%)

26 (42.6%)
24 (39.3%)
7 (11.5%)
4 (6.6%)
78.6 28
28 (45.9%)
24.2 8
41 (67.2%)
24 (39.3%)
4.5 2.8
1.5 1.4
6.8 3.1
23.5 3.9
13 (21.3%)
5.6 3.2
0.4 1.6
12 (19.7%)
5 (8.2%)
174 34
105.1 30

158 (60.8%)
102 (39.2%)

84 (32.3%)
127 (48.8%)
39 (15%)
10 (3.8%)
89.8 15
166 (63.8%)
27.3 6
192 (73.8%)
135 (51.9%)
5.6 2.4
1.4 1.6
5.9 3.2
24.7 3.5
85 (32.7%)
6.9 2.7
0.4 0.7
37 (14.2%)
15 (5.8%)
199.3 35
116.5 31

Table 2
Multiple regression analysis model
P-value

Lawton Index
0.62
Spanish version of the
0.13
Mini-Mental State Examination
Nutritional assessment
0.93
questionnaire
Chronically prescribed drugs 0.24
Tinetti Gait Scale
0.83
Barthel Index
0.0001

451

Odds ratio
0.73
1.03

1.04

0.86
1.01
1.02

0.64

0.29
0.001
0.01
0.001
0.29
0.07
0.005
0.52
0.04
0.01
0.08
0.002
0.86
0.28
0.48
0.001
0.01

95 % Confidence
Interval
0.79-1.13
0.98-1.08

0.91-1.15

0.83-1.01
0.74-1.21
1.01-1.04

The Journal of Nutrition, Health & Aging

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HIGH-DENSITY LIPOPROTEIN CHOLESTEROL IN OCTOGENARIANS

Discussion

There is no consensus regarding the lipid profile considered

characteristic of the very elderly population. Some studies have
reported that centenarians show a lipid profile similar to that of
the middle-aged population, while others have demonstrated
lower total and HDL cholesterol levels at this extreme age (3).
In the Mediterranean region, where this study was conducted,
HDL-C values are expected to be higher than in other areas
(25). In a previous study conducted in our area in a group of
subjects nearly ten years older than those in the present study
(mean age 94 years old) (12), we found a higher proportion of
subjects with low HDL-C serum values (25.8%) than was the
case in the current sample (19%).
The mean HDL-C level was 56.5 15 mg/dl, similar to the
value found in nonagenarians (60 mg/dl) but higher than that
reported in the ilSIRENTE study conducted in the Sirente
geographic area (Italy) (7). In this sample of Spanish
octagenarians the presence of gender differences in the HDL-C
means values was confirmed (59.3 in women vs. 52.1 mg/dl in
men).
The main finding of this study is that it confirms the
relationship between serum HDL-C values and functional status
(BI) that was previously reported in the NonaSantfeliu study
(12). These results are consistent with those previously reported
for subjects enrolled in the ilSIRENTE study (8), which found
that higher levels of HDL-C are associated not only with
functional status but also with better physical performance (4 m
walking speed and short physical performance battery scores).
Similarly, it has been reported that in non-disabled persons
(mean age 73.7), HDL-C levels are highly correlated with knee
extension torque and walking speed (26). The mechanism
behind this association is unknown, although it has been argued
that low HDL-C levels, by increasing the risk of ischemic heart
disease, stroke and peripheral artery disease, could, in turn,
cause a decline in lower extremity performance and muscle
strength (27). However, Volpato et al. (26) argued that rather
than interpreting their results as suggesting a protective effect
of HDL-C on the atherosclerotic process, it was necessary to
explain the association between low HDL-C and functional
impairment. Moreover, in addition to the beneficial role of
regular exercise in terms of increased HDL, HDL-C has been
found to confer additional metabolic properties that may
explain atheroprotection and could preserve quality of life and
promote longevity (26). Currently, one of the main lines of
research aimed at a better understanding of the association
between HDL-C and functional status is focused on the
possible role of inflammation. Thus, Cesari et al. (28) recently
suggested that in the presence of low HDL-C levels there is a
strong association between inflammatory biomarkers and
physical function.
In addition to the association with the BI, the bivariate
analysis also revealed interesting associations that were not
confirmed in the multivariate analysis. Specifically, subjects

452

with lower HDL-C values had poor LI scores (another test of

function), lower MEC scores, poor MNA scores and poor gait
performance (Tinetti), and were also taking more chronically
prescribed drugs. The LI and Tinetti Gait Scale associations are
probably related to the association between HDL-C values and
physical function. However, the relationship between HDL-C
and cognitive status merits more detailed discussion because
there is no consensus on this topic. Indeed, the role of HDL-C
in the risk for and progression of cognitive impairment remains
unclear, not to say controversial (29). Few studies have
evaluated the association between dementia and specific
lipoprotein fractions, although some authors have reported that
low HDL-C is correlated with cognitive impairment and
dementia, suggesting that part of this association might be
independent of atherosclerotic disease (30, 31). In the present
study we found that 85-year-old subjects with low HDL-C
scores had worse cognitive functioning (in terms of MEC
values), although this relationship was not maintained in the
multivariate analysis. A similar result was previously reported
in nonagenarians in our area (12).
The MNA has been extensively used to identify the risk of
malnutrition in the elderly. A previous Octabaix evaluation
showed that lower MNA scores correlated with a greater
likelihood of having lower vitamin D serum values (14), as is
the case with lower HDL-C serum values in the present study.
Finally, the bivariate analysis showed significantly more
polypharmacy and a tendency toward higher scores on the
Charlson Index in the low HDL-C subgroup.
One of the main strengths of the present study is the
population-based design: our unselected sample is
representative of the population aged 85 years in a mostly
Caucasian community. Moreover, the geriatric tools used in the
study are all validated and commonly used. On the other hand,
the main limitation of this study is that lipid levels were
measured only once, which could have led to measurement
error and an underestimation of the association between HDLC levels and the factors evaluated. It should also be borne in
mind that the use of HDL-C values suggested by the European
Society of Cardiology (which are good for identifying adult
subjects with increased risk) may not be useful to define low
HDL-C in a sample of Spanish 85-year-old subjects.
Furthermore, we did not adjust for confounders such as use of
lipid-lowering drugs, smoking habits, alcohol use and physical
exercise, all of which can strongly impact on HDL-C levels.
Finally, the cross-sectional design does not enable a causal
relationship to be established between scores on the measures
of functional status and HDL-C levels.
Conclusions

This study demonstrates that among 85-year-old persons

living in the community, high levels of HDL-C are
independently associated with a better functional status.

The Journal of Nutrition, Health & Aging

Volume 16, Number 5, 2012

JNHA: NUTRITION

Acknowledgments: Members of the Octabaix Study: J Almeda (Unitat de Suport a la

Recerca de Costa de Ponent, IDIAP J Gol), T Badia (ABS Martorell Urbano), C Llopart
(ABS Sant Andreu de la Barca), C Fernndez (CAP Rambla), A Ferrer (CAP El Pla), F
Formiga (UFISS de Geriatra. Servicio de Medicina Interna, Hospital Universitari de
Bellvitge), A Gil (ABS Sant Andreu de la Barca), MJ Megido (ABS Just Oliveras), G
Padrs (Laboratori Clnic LHospitalet-Cornell), M Sarr (CAP Florida Nord), A Tobella
(ABS Martorell Rural).
Financial disclosure: We declare that we have no conflict of interest;

This study was supported by public funding from the Fondo de Investigacin SanitariaInstituto de Salud Carlos III, Spain (Number PS09/00552).

1.

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