Effect of Age on Interdependence and Hierarchy of Cardiovascular

Risk Factors in Hypertensive Patients

Gregory Vyssoulis, PhDa, Evangelia Karpanou, MD, PhDb, Dionysios Adamopoulos, MDa,c,
Vassiliki Tzamou, MDa, Christodoulos Stefanadis, PhDa, and Ulrich M. Vischer, MDc,d,*
The prognostic significance, interdependence, and hierarchy of cardiovascular risk factors
could evolve with advancing age. Our study reports on the interdependence among blood
pressure (BP), other metabolic syndrome components, and high-sensitivity C-reactive
protein according to age in hypertensive subjects. A total of 5,712 nondiabetic patients
(50.1% men, age range 40 to 95 years) evaluated in outpatient hypertension clinics were
included and divided into 5 age groups (age 40 to 49, 50 to 59, 60 to 69, 70 to 79, and >80
years). BP, evaluated by both office and 24-hour ambulatory BP monitoring, and the
metabolic and inflammation parameters were determined after a >2-week drug washout
period. The prevalence of the metabolic syndrome (Adult Treatment Panel III definition)
remained stable across the age groups. We observed a stable or increased association
between waist circumference and insulin resistance (Homeostasis Model of Assessment–
Insulin Resistance index) and fasting plasma glucose. However, the association between
waist circumference and ambulatory BP monitoring systolic BP (r2 decrease from 9.9% to
1.0%, p <0.001), high-density lipoprotein cholesterol (r2 decreased from 21% to 4.9%, p ⴝ
0.002), and triglyceride levels (r2 decreased from 17.5% to 1.9%, p <0.001) decreased with
age. High-sensitivity C-reactive protein correlated with all metabolic syndrome compo-
nents in all age groups (p <0.001 for all). It became the strongest determinant of ambu-
latory BP monitoring systolic BP (p <0.001) and high-density lipoprotein cholesterol
(p <0.05) in patients >80 years old. In contrast, its association with waist circumference
markedly decreased. In conclusion, hypertension and dyslipidemia, but not fasting plasma
glucose, dissociate from central obesity with advancing age. They are increasingly deter-
mined by low-grade inflammation, independently of central obesity. These changing asso-
ciations might underlie the weakening of obesity as a cardiovascular risk factor in older
persons. © 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:240 –245)

The prognostic significance, interdependence, and hier-
archy of cardiovascular risk factors might evolve with ad-
vancing age. The study of the interdependence of these risk
factors, in particular the metabolic syndrome (MS) compo-
nents, is compounded because they are usually considered
as binary variables and defined by specific cutoffs.1,2 Al-
though this approach is convenient in clinical practice, it
fails to take into account that the MS components, not only
coexist, but also correlate in severity. Studies in which the
MS components were analyzed as continuous variables
have suggested that the blood pressure (BP), fasting plasma
glucose, high-density lipoprotein (HDL) cholesterol, and
triglycerides levels correlate with the body mass index or
a
Hypertension Unit, First Cardiology Department, “Hippokration”
Hospital, Athens, Greece; bHypertension Centre, Onassis Cardiac Surgery
Center, Athens, Greece; cDepartment of Rehabilitation and Geriatrics,
Geneva University Hospitals, Geneva, Switzerland; and dDepartment of
Cell Physiology and Metabolism, Faculty of Medicine, Geneva, Switzer-
land. Manuscript received January 5, 2011; manuscript received and ac-
cepted March 11, 2011.
UMV is supported by the Swiss National Science Foundation, grant
320030-134973.
*Corresponding author: Tel: (⫹41) 22-305-6310; fax: (⫹31) 22-305-
6115.
E-mail address: ulrich.vischer@hcuge.ch (U.M. Vischer).
insulin resistance.3–5 However, the associations between
these risk factors may be overestimated (and the lessening
of these associations underestimated) by analyses of the
binary variables, in particular, when low cutoffs (using the
recent MS definitions) are used. Another important issue is
the stability and reproducibility of the risk factor measure-
ments. This is particularly problematic with BP. Office BP
values are much more variable and higher than ambulatory
BP monitoring (ABPM) values. However, the latter are
more strongly associated with the risk of cardiovascular
events6 and should therefore be used to study the interde-
pendence of the MS components (whether analyzed as bi-
nary or continuous variables). The aim of the present study
was to determine the associations among BP, other MS
components, and low-grade inflammation and their evolu-
tion with age in a large cohort of patients with office
hypertension.
Methods
The hypertension outpatient clinics of the “Hippokra-
tion” and “Onassis” Hospitals (Athens, Greece) offer com-
prehensive hemodynamic and metabolic evaluations to hy-
pertensive patients, usually referred by their general
practitioners. The detailed evaluation procedures used have
been previously reported.7,8 At the initial visit, a medical

0002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved. www.ajconline.org
doi:10.1016/j.amjcard.2011.03.035

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 Systemic Hypertension/Cardiovascular Risk Factor Interdependence and Aging 241

Table 1
Demographic, hemodynamic, and metabolic characteristics of study population according to age group
Variable Age Group (years) p
Value
40–49 50–59 60–69 70–79 ⱖ80

Patients (n) 1,119 1862 1559 895 277

Men 56.7% 50.9% 47.9% 46.7% 40.8% ⬍0.001
Office blood pressure (mm Hg)
Systolic 161 ⫾ 11 165 ⫾ 10 168 ⫾ 8 171 ⫾ 7 177 ⫾ 8 ⬍0.001
Diastolic 105 ⫾ 5 102 ⫾ 6 98 ⫾ 7 92 ⫾ 7 86 ⫾ 7 ⬍0.001
Ambulatory blood pressure monitoring (mm Hg)
Systolic 134 ⫾ 12 134 ⫾ 11 135 ⫾ 10 137 ⫾ 10 140 ⫾ 11 ⬍0.001
Diastolic 86 ⫾ 8 84 ⫾ 7 81 ⫾ 7 77 ⫾ 6 75 ⫾ 6 ⬍0.001
Never treated patients 68.5% 59.9% 47.9% 41.1% 40.8% ⬍0.001
Waist circumference (cm) 95.0 ⫾ 14.2 95.5 ⫾ 12.8 94.8 ⫾ 13.1 94.0 ⫾ 11.8 94.0 ⫾ 11.9 0.037
Body mass index (kg/m2) 28.5 ⫾ 4.9 28.7 ⫾ 4.4 28.3 ⫾ 4.5 27.6 ⫾ 4.2 27.3 ⫾ 4.5 ⬍0.001
Body mass index ⱖ30 kg/m2 31.5% 35.1% 32.9% 25.7% 22.0% ⬍0.001
Total cholesterol (mg/dl) 213 ⫾ 38 215 ⫾ 37 216 ⫾ 38 210 ⫾ 38 205 ⫾ 34 ⬍0.001
High-density lipoprotein cholesterol (mg/dl) 48.6 ⫾ 12.1 50.8 ⫾ 12.8 52.6 ⫾ 13.4 53.5 ⫾ 13.9 51.9 ⫾ 13.6 ⬍0.001
Low-density lipoprotein cholesterol (mg/dl) 139.1 ⫾ 34.4 139.5 ⫾ 33.2 139.4 ⫾ 33.9 133.8 ⫾ 34.9 128.3 ⫾ 31.1 ⬍0.001
Triglycerides (mg/dl) 126.4 ⫾ 65.6 124.1 ⫾ 61.9 119.3 ⫾ 51.3 115.5 ⫾ 52.0 124.0 ⫾ 57.3 0.006
Fasting plasma glucose (mg/dl) 94.5 ⫾ 12.3 97.0 ⫾ 12.3 99.2 ⫾ 13.2 99.0 ⫾ 13.7 100.5 ⫾ 13.8 ⬍0.001
Homeostasis Model of Assessment–Insulin 2.31 ⫾ 1.12 2.34 ⫾ 1.07 2.37 ⫾ 1.11 2.32 ⫾ 0.94 2.37 ⫾ 0.97 0.6
Resistance
High-sensitivity C-reactive protein (mg/dl) 1.33 ⫾ 1.08 1.43 ⫾ 1.14 1.44 ⫾ 1.10 1.49 ⫾ 1.07 1.75 ⫾ 1.13 ⬍0.001
Smokers 49.1% 40.2% 31.6% 22.3% 18.4% ⬍0.001

Table 2
Prevalence of metabolic syndrome and it components according to age group
Variable Age Group (years) p Value

40–49 50–59 60–69 70–79 ⱖ80

High blood pressure* 100% 100% 100% 100% 100%

High waist circumference* 41.6% 47.1% 47.3% 45.0% 49.1% 0.016
Low high-density lipoprotein cholesterol* 35.8% 32.4% 28.0% 28.2% 30.7% ⬍0.001
High triglycerides* 29.1% 26.7% 25.1% 23.9% 26.0% 0.071
High fasting plasma glucose* 11.7% 15.4% 21.4% 21.9% 26.0% ⬍0.001
Metabolic syndrome components (n) 2.18 ⫾ 1.13 2.22 ⫾ 1.13 2.22 ⫾ 1.15 2.19 ⫾ 1.16 2.32 ⫾ 1.17 0.476
Metabolic syndrome 35.1% 36.2% 35.9% 34.7% 38.6% 0.782

* Defined according to Adult Treatment Panel III (2001) criteria.2

history and physical examination (including height, weight,
and waist and hip circumference measurements) were per-
formed in all subjects. All patients receiving therapy for
arterial hypertension or dyslipidemia underwent a complete
washout period of ⱖ15 days.
The office BP, measured with mercury sphygmomanom-
eters, was recorded at the second visit as the mean of 3
values, taken with the patient seated, 1 minute apart. Arte-
rial hypertension was defined as the elevation of either
systolic or diastolic BP ⬎140/90 mm Hg or the use of
antihypertensive drugs for ⱖ6 months. All patients under-
went 24-hour ABPM using the nondominant arm with a
Spacelabs 90207 device (SpaceLabs, Redmond, Washing-
ton). The recorder was set to take readings at 20-minute
intervals from 6:00 A.M. to 10:00 P.M. and every 30 minutes
from 10:00 P.M. to 6:00 A.M. The recording was analyzed to
obtain the 24-hour average systolic and diastolic BP values.
The total, low-density lipoprotein, and HDL cholesterol,
triglycerides, fasting plasma glucose, insulin levels, and
high-sensitivity C-reactive protein (hs-CRP) were measured
using blood serum or plasma collected after the patient had
fasted overnight. Insulin resistance was estimated using the
Homeostasis Model of Assessment–Insulin Resistance in-
dex.9 The MS was defined according to the Adult Treatment
Panel III criteria.2
For the present study, only nondiabetic patients with
office hypertension (office systolic BP ⬎140 mm Hg and/or
diastolic BP ⬎90 mm Hg), for whom an ABPM, hs-CRP,
fasting plasma glucose, and insulin levels were available,
were included. The population was divided into 5 groups by
age decade (40 to 49, 50 to 59, 60 to 69, 70 to 79, and ⱖ80
years). The baseline parameters were compared among the
age groups using analysis of variance or chi-square tests, as
appropriate. The normality of the parameters was assessed
by histograms and Q–Q plots; in the case of significant
deviation from a normal distribution, a log transformation
was applied.
The age-related progression of the associations between
the ABPM systolic BP, waist circumference, and hs-CRP

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242 The American Journal of Cardiology (www.ajconline.org)

Table 3
Associations among systolic blood pressure (BP), high-density lipoprotein (HDL) cholesterol, and high-sensitivity C-reactive protein (hs-CRP) and other
metabolic syndrome components according to age group
Age Group (years) p Value Model
R2
40–49 50–59 60–69 70–79 ⱖ80 Overall Interaction
(Referent) Effect

Ambulatory blood pressure monitoring-systolic

blood pressure
Waist circumference 0.375 0.356 0.352 0.188* 0.011* ⬍0.001 ⬍0.001 7.9
9.9 9.6 7.6 2.4 0.01
High-density lipoprotein cholesterol ⫺0.23 ⫺0.23 ⫺0.29 ⫺0.28 ⫺0.18 ⬍0.001 0.48 5.9
5.3 4 4.8 4 2.1
Log_triglycerides 0.004 0.003 0.003 0.003 0.004 ⬍0.001 0.31 2.9
4.2 2.1 1.7 2.3 4.2
Fasting plasma glucose 0.145 0.159 0.220 0.213 0.042 ⬍0.001 0.11 4.2
2 2.1 2.9 2.3 0.1
Homeostasis Model of Assessment–Insulin 0.022 0.02 0.028 0.024 0.017 ⬍0.001 0.14 5.5
Resistance 5.5 4.2 6.6 6.2 3.5
Log_high-sensitivity C-reactive protein 0.009 0.008 0.011 0.008 0.012 ⬍0.001 0.06 8.7
8.1 6.5 9.8 5.5 12.8
Waist circumference
Ambulatory blood pressure monitoring- 0.264 0.269 0.216 0.130* 0.009* ⬍0.001 ⬍0.001 9.7
systolic blood pressure 9.9 9.6 7.6 2.4 0.01
High-density lipoprotein cholesterol ⫺0.386 ⫺0.473† ⫺0.441 ⫺0.392 ⫺0.251‡ ⬍0.001 0.002 19.4
20.5 22.6 18.6 11.1 4.9
Log_triglycerides 0.006 0.005‡ 0.004* 0.004‡ 0.002* ⬍0.001 ⬍0.001 10.9
17.5 10.4 7.6 8.1 1.9
Fasting plasma glucose 0.226 0.298‡ 0.297‡ 0.312‡ 0.425† ⬍0.001 0.023 10.5
6.8 9.6 8.6 7.2 13.4
Homeostasis Model of Assessment–Insulin 0.038 0.038 0.036 0.032 0.043 ⬍0.001 0.205 20.7
Resistance 23.7 21.4 18.2 16.8 28.9
Log_high-sensitivity C-reactive protein 0.009 0.01 0.009 0.006† 0.005‡ ⬍0.001 0.001 10.4
11.1 12.1 9.6 3.8 2.5
Log_high-sensitivity C-reactive protein
Waist circumference 12.2 12 11.3 6.5* 5.2† ⬍0.001 ⬍0.001 9.9
11.1 12.1 9.6 3.8 2.5
Ambulatory blood pressure monitoring- 8.73 7.64 8.56 6.5 10.29 ⬍0.001 0.182 9.8
systolic blood pressure 8.1 6.5 9.8 5.5 12.8
High-density lipoprotein cholesterol ⫺7.43 ⫺9.65 ⫺8.24 ⫺8.51 ⫺6.91 ⬍0.001 0.403 7.5
5.8 7.9 5.4 4.7 3.4
Log_triglycerides 0.11 0.12 0.1 0.11 0.13 ⬍0.001 0.918 5.0
4.3 4.9 4.6 4.4 6.8
Fasting plasma glucose 6.19 5.35 7.93 7.44 8.56 ⬍0.001 0.164 5.9
3.8 5.6 5.1 3.7 5.0
Homeostasis Model of Assessment–Insulin 0.96 0.88 0.97 0.74 1.04 ⬍0.001 0.284 10.3
Resistance 11.1 9.5 10.9 7.7 14.8

Data are presented as unstandardized beta and R2 (upper and lower line respectively) obtained from multiple linear regression analysis.
* p ⬍0.001; † p ⬍0.01; ‡ p ⬍ 0.05 compared to reference age category (40 to 49 years).

with the MS components was assessed by multiple linear
regression models, including the age variable (categorical
data age groups), the independent variable tested, and their
interactions (each time-independent variable tested ⫻ age
group interaction). The independent determinants of the MS
components were identified and compared in patients ⬍60
years old and ⬎80 years old by stepwise backward multiple
linear regression models, including the following variables:
ABPM systolic BP, waist circumference, HDL cholesterol,
log_triglycerides, gender, fasting plasma glucose, log_hs-
CRP, and smoking. Each was tested with the 7 others as
independent variables. To allow comparisons between the
relative effects of each determinant on the dependent vari-
able, the results of the multiple regression analyses are
expressed equally for a change from the 5th to the 95th
percentile. Significance was assumed at a level of p ⬍0.05.
The results for ABPM-systolic BP and HDL cholesterol are
shown. All analyses were performed using the Statistical
Package for Social Sciences, version 13.0 (SPSS, Chicago,
Illinois).
Results
The final study population included 5,712 nondiabetic
patients with office hypertension (50.1% men). Their gen-
eral characteristics according to age group are listed in
Table 1. As expected, the ABPM mean values were lower
than the office BP values, with an age-related increase in the

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 Systemic Hypertension/Cardiovascular Risk Factor Interdependence and Aging 243

Figure 1. Correlation scatter plots and regression lines between ambulatory systolic BP and waist circumference according to age group (waist ⫻ age group
interaction, p ⬍0.001).

Table 4
Independent determinants of ambulatory blood pressure monitoring (ABPM) systolic blood pressure (BP) and high-density lipoprotein (HDL) cholesterol
in hypertensive patients ⬍60 compared to ⬎80 years old
Patients Aged ⬎80 years Patients Aged ⬍60 years

Ambulatory blood pressure monitoring-systolic blood pressure

Model R2 14.2% Model R2 13.4%
Log_high-sensitivity C-reactive protein (per 11.2* (7.3, 15.1) Gender (men vs women) 1.1† (0.1, 2.1)
1.16 log_mg/dl change)
Log_triglycerides (per 0.62 log_mg/dl change) 4.4† (0.2, 8.5) Smoking status (smokers vs nonsmokers) 1.0† (0.2, 1.8)
Waist circumference (per 44 cm change) 7.2* (5.5, 8.9)
Log_high-sensitivity C-reactive protein (per 6.0* (4.7, 7.3)
1.16 log_mg/dl change)
Fasting plasma glucose (per 42 mg/dl change) 1.6† (0.3, 3.0)
High-density lipoprotein cholesterol
Model R2 31.7% Model R2 35.4%
Gender (men vs women) ⫺10.82* (⫺13.6, ⫺8.1) Gender (men vs women) ⫺8.0* (⫺8.9, ⫺7.2)
Log_high-sensitivity C-reactive protein (per ⫺5.1† (⫺9.6, ⫺0.6) Smoking status (smokers vs nonsmokers) ⫺2.1* (⫺2.9, ⫺1.4)
1.16 log_mg/dl change)
Log_triglycerides (per 0.62 log_mg/dl change) ⫺16.3* (⫺21.0, ⫺11,6) Waist circumference (per 44 cm change) ⫺6.5*
(⫺8.1, ⫺5.0)
Log_triglycerides (per 0.62 log_mg/dl ⫺8.7* (⫺9.9, ⫺7.5)
change)
Log_high-sensitivity C-reactive protein (per ⫺4.1* (⫺5.3, ⫺2,9)
1.16 log_mg/dl change)

Data are presented as unstandardized ␤ coefficients for change from 5th to 95th percentile, obtained from backward, stepwise multiple linear regression
analysis.
* p ⬍0.001; † p ⬍0.05.

systolic BP and decrease in the diastolic BP for both office
and ABPM measurements. We observed a progressive de-
crease in the body mass index and minor (although statis-
tically significant) changes in the waist circumference and
lipid levels. Fasting plasma glucose, but not the Homeosta-
sis Model of Assessment–Insulin Resistance values, signif-
icantly increased with age. The hs-CRP values also signif-
icantly increased with age. Overall, the prevalence of the
MS remained quite stable with advancing age (Table 2). The
age-related increase in the prevalence of a high waist cir-
cumference and fasting plasma glucose was counterbal-
anced by a decreasing prevalence of dyslipidemia.
The interdependence between the risk factors and the
interaction with age were studied using multiple linear re-
gression models, with each risk factor as a continuous vari-
able (Table 3). We observed a strong, significant association
between the ABPM systolic BP and waist circumference
and weaker associations with HDL cholesterol, triglycer-
ides, fasting plasma glucose, and Homeostasis Model of
Assessment–Insulin Resistance in the younger age groups.

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244 The American Journal of Cardiology (www.ajconline.org)
A gradual decrease was seen with advancing age in the
association between the ABPM systolic BP and waist cir-
cumference (p ⬍0.001 for interaction) that was not seen
with the other MS components (Figure 1 and Table 3). The
relatively strong association between the ABPM systolic BP
and hs-CRP apparently increased with age, although the age
effect failed to reach statistical significance. The waist cir-
cumference, used as the dependent variable, was quite
strongly associated with the ABPM systolic BP, HDL cho-
lesterol, triglycerides, and fasting plasma glucose in the
younger age groups (Table 3). These associations were
stronger using the waist circumference than using the body
mass index (data not shown). The association between the
waist circumference and Homeostasis Model of Assess-
ment–Insulin Resistance and fasting plasma glucose re-
mained stable or increased with age. In contrast, the asso-
ciation with ABPM systolic BP, HDL cholesterol, and
triglycerides disappeared or markedly decreased with age.
Thus, the BP and lipid levels (but not fasting plasma glu-
cose) were dissociated from obesity with advancing age.
We next explored the age-related effect of hs-CRP on the
interdependence of the MS components. High-sensitivity
CRP was associated with waist circumference, the Homeo-
stasis Model of Assessment–Insulin Resistance, and other
MS components (Table 3). The association with waist cir-
cumference markedly decreased with age, but the associa-
tion with the Homeostasis Model of Assessment–Insulin
Resistance and other MS components did not change sig-
nificantly.
We finally compared the independent risk factors asso-
ciated with ABPM systolic BP and HDL cholesterol in
patients ⬎80 years old versus those aged ⬍60 years (Table
4). Both these risk factors were associated with multiple
parameters in patients ⬍60 years old. However, in patients
⬎80 years old, hs-CPR and triglycerides remained the only
parameters significantly associated with ABPM systolic BP
and HDL cholesterol. A 1.16 log_mg/dl increase in log_hs-
CRP, corresponding to an increase from 0.25 to 3.3 mg/dl
(5th to 95th percentile), was associated with an 11.2-mm Hg
increase in ABPM systolic BP and a 5.1-mg/dl decrease in
HDL cholesterol.
Discussion
Our data have demonstrated that the interdependence of
the MS components decreases with age. Systolic BP was
associated with waist circumference, the Homeostasis
Model of Assessment–Insulin Resistance, HDL cholesterol,
and fasting plasma glucose in young adults. However, these
associations disappeared or markedly decreased in older
patients. The waist circumference is considered the com-
mon denominator of the MS. It was strongly associated with
the Homeostasis Model of Assessment–Insulin Resistance,
HDL cholesterol, triglycerides, fasting plasma glucose, and
systolic BP in young adults, as predicted. However, with
increasing age, the association among the waist circumfer-
ence, Homeostasis Model of Assessment–Insulin Resis-
tance, and fasting plasma glucose increased and the associ-
ation with systolic BP, HDL cholesterol, and triglycerides
disappeared or markedly decreased. These findings strongly
suggest that with advancing age, hypertension and dyslipi-
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demia are increasingly associated with factors distinct from
central obesity or insulin resistance. One important age-
related risk factor is low-grade inflammation, as assessed by
hs-CRP. hs-CRP increased with age and remained associ-
ated with insulin resistance but not with waist circumfer-
ence. Also, hs-CRP was the parameter most strongly asso-
ciated with both systolic BP and HDL cholesterol in patients
⬎80 years old, more strongly than the other MS compo-
nents.
The cardiovascular risk associated with obesity markedly
decreases with age.10 This can be, at least in part, accounted
for by the weakening associations between the waist cir-
cumference and BP and lipid levels. Our findings were not
wholly unexpected. In “young” adults, obesity and/or insu-
lin resistance are associated with BP by multiple potential
mechanisms.11–13 In contrast, with advancing age, arterial
stiffness becomes a major determinant of BP, causing an
increase in the systolic BP and a decrease in the diastolic
BP. Thus, the BP is increasingly determined by accumu-
lated vascular damage, largely independent of the presence
of obesity or insulin resistance at the time of the assess-
ment.14 Insulin resistance and central obesity are also major
determinants of the triglycerides and HDL cholesterol levels
in adults, because of an increase in circulating free fatty acid
levels, leading to the formation and release of triglyceride-
rich very-low-density lipoprotein particles. Triglycerides
are exchanged for esterified cholesterol from HDL particles,
leading to a decrease in HDL cholesterol.15 HDL choles-
terol is associated with adiponectin levels, which are low in
the presence of insulin resistance.16,17 However, inflamma-
tion can induce an increase in triglycerides and a decrease in
HDL cholesterol, possibly by the activation of lipoprotein
lipase or endothelial lipase.15,18 Thus, the age-related in-
crease in low-grade inflammation might compound the as-
sociation between insulin resistance or obesity and dyslip-
idemia. Low-grade inflammation has actually been
implicated as a key mediator between obesity and insulin
resistance.19,20 It is worth noting that in our study the
association between hs-CRP and waist circumference pro-
gressively decreased with advancing age, arguing against a
major role for obesity in the low-grade inflammation ob-
served in older subjects.
A key issue in the MS is the recognition that several risk
factors are clustered, with obesity and/or insulin resistance
as common denominators. This implies that a reduction in
body weight and insulin resistance is expected to also im-
prove the associated risk factors. The Diabetes Prevention
Program (DPP) and other studies showed that weight loss
reduces the risk of diabetes, hypertension, and dyslipidemia
in patients with prediabetes or the MS.21–23 Our observa-
tions suggest that the improvement in these risk factors from
weight loss per se might be less predictable in older sub-
jects. These considerations do not deny the importance of
lifestyle modifications in the prevention of diabetes and
possibly functional impairments in even old obese/over-
weight subjects.22,24 –26
Our study had several limitations. We reported on a
nonrandom study population recruited from specialty clin-
ics, rather than a general population sample. The referral to
a specialty clinic on a voluntary basis might have biased the
recruitment toward relatively health-conscious patients. The
 Systemic Hypertension/Cardiovascular Risk Factor Interdependence and Aging
prevalence of the associated risk factors might have been
lower in our study group than in the general population.
Furthermore, we did not have complete follow-up data on
cardiovascular events or mortality and, therefore, could not
determine whether the MS or its components remained
significant risk factors with advancing age. Antihyperten-
sive and lipid-lowering drugs were withdrawn ⬎2 weeks
before the patient assessments. A carryover effect of these
drugs might have led to an underestimation of the associa-
tions between the risk factors but would be unlikely to
account for the effect of age on these associations. In con-
trast, the major strength of the study was the large popula-
tion size of drug-free subjects and the very comprehensive
evaluation, including insulin levels and ABPM recordings,
providing a quite unique opportunity to study the interde-
pendence of the risk factors included in the MS.
1. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato
KA, Fruchart JC, James WP, Loria CM, Smith SC Jr. Harmonizing the
metabolic syndrome: a joint interim statement of the International
Diabetes Federation Task Force on Epidemiology and Prevention;
National Heart, Lung, and Blood Institute, American Heart Associa-
tion; World Heart Federation; International Atherosclerosis Society;
and International Association for the Study of Obesity. Circulation
2009;120:1640 –1645.
2. Expert Panel on Detection, Evaluation and Treatment of High Blood
Cholesterol in Adults. Executive Summary of the Third Report of the
National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation, and Treatment of High Blood cholesterol in
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