Lower the triglyceride,
longer the survival
......................................................................................................................................................................
Mehmet Rami Helvaci (1)
Orhan Ayyildiz (1)
Orhan Ekrem Muftuoglu (1)
Mehmet Gundogdu (1)
Abdulrazak Abyad (2)
Lesley Pocock (3)
(1) Professor of Internal Medicine,
MD
(2) Middle-East Academy for Medicine of Aging,
MD, MPH, MBA, AGSF
(3) medi+WORLD International
Correspondence:
Mehmet Rami Helvaci, M.D.
07400, ALANYA, Turkey
Phone: 00-90-506-4708759
Email: mramihelvaci@hotmail.com
ABSTRACT
Background: We tried to determine
the safest triglyceride value in the plasma.
Methods: Check up cases with a triglyceride
value lower than 60 mg/dL were collected
into the first, lower than 100 mg/dL into
the second, lower than 150 mg/dL into the
third, lower than 200 mg/dL into the fourth,
and equal to or greater than 200 mg/dL into
the fifth groups, respectively.
Results: Study included 478 cases
(288 females and 190 males), totally. Mean
values of age, body weight, body mass index,
triglyceride, and low density lipoprotein
cholesterol and prevalences of smoking,
white coat hypertension (WCH), hypertension,
type 2 diabetes mellitus (DM), and coronary
artery disease (CAD) increased nearly in
all steps from the first towards the fifth
groups, gradually and significantly (p<0.05).
Conclusions: Probably metabolic syndrome
is a chronic inflammatory process mainly
affecting the vascular endothelium all over
the body and terminating with early aging
and premature death. The syndrome has reversible
parameters including sedentary life style,
animal-rich diet, overweight, smoking, alcohol,
hypertriglyceridemia, hyperbetalipoproteinemia,
dyslipidemia, impaired fasting glucose,
impaired glucose tolerance, WCH, chronic
inflammations and infections and irreversible
end points including obesity, hypertension,
DM, cirrhosis, peripheric artery disease,
chronic obstructive pulmonary disease, chronic
renal disease, CAD, mesenteric ischemia,
osteoporosis, and stroke. Hypertriglyceridemia
may be one of the most significant reversible
parameters of the syndrome, and it is better
to have the lowest plasma triglyceride value
as much as possible to live longer.
Key words: Triglyceride, metabolic
syndrome, atherosclerosis, early aging,
premature death
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Chronic endothelial damage may
be the most common kind of vasculitis and the
leading cause of aging, morbidity, and mortality
in human beings (1-4). Much higher blood pressure
(BP) of the afferent vasculature may be the major
underlying cause by inducing recurrent injuries
on endothelium, and probably whole afferent vasculature
including capillaries are involved in the process.
Thus the term of venosclerosis is not as famous
as atherosclerosis in the literature. Secondary
to the chronic endothelial inflammation, edema,
and fibrosis, vascular walls become thickened,
their lumens are narrowed, and they lose their
elastic natures that reduce blood flow to terminal
organs and increase systolic BP further. Some
of the well-known causes and indicators of the
inflammatory process are sedentary life style,
animal-rich diet, overweight, smoking, alcohol,
hypertriglyceridemia, hyperbetalipoproteinemia,
dyslipidemia, impaired fasting glucose (IFG),
impaired glucose tolerance (IGT), white coat hypertension
(WCH), and chronic inflammatory processes including
rheumatologic disorders, chronic infections, and
cancers for the development of terminal complications
including obesity, hypertension, diabetes mellitus
(DM), cirrhosis, peripheric artery disease (PAD),
chronic obstructive pulmonary disease (COPD),
chronic renal disease (CRD), coronary artery disease
(CAD), mesenteric ischemia, osteoporosis, and
stroke, all of which terminate with early aging
and premature death (5-9). Although early withdrawal
of causative factors may prevent irreversible
complications, after development of cirrhosis,
COPD, CRD, CAD, PAD, or stroke, endothelial changes
cannot be reversed completely due to their fibrotic
nature. The accelerator factors and terminal consequences
were researched under the titles of metabolic
syndrome, aging syndrome, or accelerated endothelial
damage syndrome in the literature, extensively
(10-13). On the other hand, although its normal
limits could not been determined clearly yet,
hypertriglyceridemia is one of the significant
indicators of the metabolic syndrome (14). Due
to the growing evidence for a strong association
between increased plasma triglyceride values and
prevalence of CAD, Adult Treatment Panel (ATP)
III adopts lower cutpoints for triglyceride abnormalities
than did ATP II (15, 16). Although ATP II determined
the normal triglyceride value as lower than 200
mg/dL in 1994, World Health Organisation (WHO)
in 1999 (17) and ATP III in 2001 reduced its normal
limit as lower than 150 mg/dL (15). Although these
cutpoints are usually used to define limits of
the metabolic syndrome, there are suspicions about
the safest limits of plasma triglyceride values
in the literature. We tried to determine the safest
triglyceride value in the plasma.
The study
was performed in the Internal Medicine Polyclinic
of the Medical Faculty of the Dumlupinar University
on routine check up patients between August 2005
and March 2007. Consecutive patients between the
ages of 15 and 70 years were studied to prevent
debility induced weight loss in elders. Their
medical histories including hypertension, DM,
dyslipidemia, and already used medications were
learnt, and a routine check up procedure including
an electrocardiography, fasting plasma glucose
(FPG), triglyceride, and low density lipoprotein
cholesterol (LDL-C) was performed. Current daily
smokers, at least with six pack-months, and cases
with a history of five pack-years were accepted
as smokers. Patients with devastating illnesses
including type 1 DM, malignancies, acute or chronic
renal failure, chronic liver diseases, hyper-
or hypothyroidism, and heart failure were excluded
to avoid their possible effects on weight. Additionally,
anti-hyperlipidemic drugs or metformin users were
excluded to avoid their possible effects on blood
lipid profile (18). Body mass index (BMI) of each
case was calculated by the measurements of the
same physician instead of verbal expressions.
Weight in kilograms is divided by height in meters
squared (15). Cases with an overnight FPG level
of 126 mg/dL or greater on two occasions or already
receiving antidiabetic medications were defined
as diabetics (15). An oral glucose tolerance test
with 75-gram glucose was performed in cases with
a FPG level between 110 and 126 mg/dL, and diagnosis
of cases with a 2-hour plasma glucose level of
200 mg/dL or greater is DM (15). Additionally,
office blood pressure (OBP) was checked after
a 5 minute rest in seated position with a mercury
sphygmomanometer on three visits, and no smoking
was permitted during the previous 2 hours. A 10-day
twice daily measurement of blood pressure at home
(HBP) was obtained in all cases, even in normotensives
in the office due to the risk of masked hypertension
after a 10-minute education session about proper
BP measurement techniques (19). An additional
24-hour ambulatory blood pressure monitoring (ABP)
was obtained just in cases with a higher OBP and/or
HBP measurement. It was performed with oscillometrical
equipment (SpaceLabs 90207, Redmond, Washington,
USA) set to take a reading every 10 minutes throughout
the 24 hours. Eventually, hypertension is defined
as a BP of 135/85 mmHg or greater on mean daytime
(between 10 AM to 8 PM) ABP, WCH as an OBP of
140/90 mmHg or greater but mean daytime ABP of
<135/85 mmHg (19). A stress electrocardiography
was performed just in suspected cases as a result
of the routine electrocardiography, and a coronary
angiography was obtained just for the stress electrocardiography
positive cases. Eventually, patients with a triglyceride
value lower than 60 mg/dL were collected into
the first, lower than 100 mg/dL into the second,
lower than 150 mg/dL into the third, lower than
200 mg/dL into the fourth, and equal to or greater
than 200 mg/dL into the fifth groups, respectively.
The female ratio, values of the mean age, weight,
BMI, triglyceride, and LDL-C, and prevalences
of smoking, WCH, hypertension, DM, and CAD were
detected in each group and compared. Mann-Whitney
U test, Independent-Samples T test, and comparison
of proportions were used as the methods of statistical
analyses.
The study included 478 cases
(288 females and 190 males), totally. The mean
ages of the groups increased up to the triglyceride
value of 200 mg/dL, significantly (p<0.05 in
all steps), then decreased nonsignificantly (50.5
versus 48.6 years, p>0.05). There were 117
smokers totally, and only 27.3% (32) of them were
females. On the other hand, prevalence of smoking
was the highest in the highest triglyceride value
having group. The mean body weight increased continuously,
parallel to the increasing value of triglyceride,
whereas BMI increased up to the triglyceride value
of 200 mg/dL, and then decreased. Similarly, the
mean LDL-C reached its the highest value in the
fourth, and decreased significantly in the fifth
groups (142.0 versus 128.5 mg/dL, p=0.008) (Table
1). Similarly again, prevalence of WCH was the
highest in the fourth, and decreased significantly
in the fifth groups (48.2% versus 32.5%, p<0.01).
As the most surprising result, prevalences of
hypertension, type 2 DM, and CAD, as the irreversible
end points of the metabolic syndrome, showed their
most significant increases after the triglyceride
value of 100 mg/dL (Table 2).
Click here for Table
1: Characteristics of the study cases
Click here for Table
2: Associated diseases of the study cases
Excess weight leads to both structural
and functional abnormalities of many systems of
the body. Recent studies revealed that adipose
tissue produces leptin, tumor necrosis factor-alpha,
plasminogen activator inhibitor-1, adiponectin,
and other cytokines which act as acute phase reactants
in the plasma (20, 21). For example, the cardiovascular
field has recently shown a great interest in the
role of inflammation in the development of atherosclerosis
and numerous studies indicated that inflammation
plays a significant role in the pathogenesis of
atherosclerosis and thrombosis (1, 2). On the
other hand, individuals with excess weight have
an increased blood volume as well as an increased
cardiac output thought to be the result of increased
oxygen demand of the excessive fat tissue. The
prolonged increase in blood volume can lead to
myocardial hypertrophy and decreased compliance
in addition to the common comorbidity of hypertension.
In addition to them, the prevalences of high FPG,
high serum total cholesterol, and low high density
lipoprotein cholesterol (HDL-C) increased parallel
to the higher BMI values (22). Combination of
these cardiovascular risk factors will eventually
lead to an increase in left ventricular stroke
work with higher risks of arrhythmias, cardiac
failure, and sudden cardiac death. Similarly,
the prevalences of CAD and stroke increased parallel
with the higher BMI values in some other studies
(22, 23), and risk of death from all causes including
cancers increased throughout the range of moderate
to severe weight excess in all age groups (24).
The relationships between excess weight and elevated
BP and hypertriglyceridemia were described in
the metabolic syndrome (14), and clinical manifestations
of the syndrome included obesity, dyslipidemia,
hypertension, insulin resistance, and proinflammatory
and prothrombotic states (12). Similarly, prevalences
of smoking (42.2% versus 28.4%, p<0.01), excess
weight (83.6% versus 70.6%, p<0.01), DM (16.3%
versus 10.3%, p<0.05), and hypertension (23.2%
versus 11.2%, p<0.001) were all higher in the
hypertriglyceridemia cases in another study (25).
It is a well-known fact that smoking causes a
chronic inflammatory process in the respiratory
tract, lungs, and vascular endothelium all over
the body terminating with an accelerated atherosclerosis,
end-organ insufficiencies, early aging, and premature
death thus it should be included among the major
parameters of the metabolic syndrome. On the other
hand, smoking-induced weight loss is probably
related with the smoking-induced endothelial inflammation
all over the body since
loss of appetite is one of the main symptoms of
disseminated inflammation in the body. In another
explanation, smoking-induced loss of appetite
is an indicator of being ill instead of being
healthy during smoking (26-28). Buerger's disease
(thromboangiitis obliterans) alone is also a clear
evidence to show the strong atherosclerotic effects
of smoking since this disease has not been shown
in the absence of smoking up to now. On the other
hand, the prevalences of hyperbetalipoproteinemia
were similar in the hypertriglyceridemia and control
groups (18.9% versus 16.3%, p>0.05, respectively)
in the above study (25).
Although ATP II determined
the normal triglyceride value as lower than 200
mg/dL in 1994 (16), WHO in 1999 (17) and ATP III
in 2001 (15) reduced this normal limit as lower
than 150 mg/dL. Although these cutpoints are usually
used to define limits of the metabolic syndrome,
whether or not more lower limits provide additional
benefits for human beings is unclear. In the present
study, patients with a triglyceride value lower
than 60 mg/dL were collected into the first, lower
than 100 mg/dL into the second, lower than 150
mg/dL into the third, lower than 200 mg/dL into
the fourth, and equal to or greater than 200 mg/dL
were collected into the fifth groups, respectively.
Prevalence of smoking was the highest in the fifth
group which may also indicate inflammatory roles
of smoking and hypertriglyceridemia in the metabolic
syndrome. The mean body weight increased continuously,
parallel to the increasing value of triglyceride.
As the most surprising result, the prevalences
of hypertension, type 2 DM, and CAD, as some of
the terminal end points of the metabolic syndrome,
showed their most significant increases after
the triglyceride value of 100 mg/dL. As of our
opinion, significantly increased mean age by the
increased triglyceride values may be secondary
to aging induced decreased physical and mental
stresses, which eventually terminates with onset
of excess weight and other parameters and terminal
end points of the metabolic syndrome. Interestingly,
although the mean age increased from the lowest
triglyceride having group towards the triglyceride
value of 200 mg/dL, then decreased. The similar
trend was also seen in the mean LDL-C and BMI
values, and prevalence of WCH. These trends may
be due to the fact that although the borderline
high triglyceride values (150-199 mg/dL) are seen
together with overweight, obesity, physical inactivity,
smoking, and alcohol like acquired causes, the
high triglyceride (200-499 mg/dL) and very high
triglyceride values (500 mg/dL and higher) are
usually secondary to both acquired and secondary
causes such as type 2 DM, chronic renal failure,
and genetic patterns (15). But although the underlying
causes of the high and very high triglyceride
values may be a little bit different, probably
risks of the terminal end points of the metabolic
syndrome do not change in these groups, too. For
example, prevalences of hypertension and type
2 DM were the highest in the highest triglyceride
value having group in the present study. Eventually,
although some authors reported that lipid assessment
in vascular disease can be simplified by measurement
of either total and HDL-C levels without the need
of triglyceride (29), the present study and most
others indicated a causal association between
triglyceride-mediated pathways and parameters
of the metabolic syndrome (30). Similarly, another
study indicated moderate and highly significant
associations between triglyceride values and CAD
in Western populations (31).
As a conclusion, probably metabolic syndrome is
a chronic inflammatory process mainly affecting
the vascular endothelium all over the body and
terminating with early aging and premature death.
The syndrome has reversible parameters including
sedentary life style, animal-rich diet, overweight,
smoking, alcohol, hypertriglyceridemia, hyperbetalipoproteinemia,
dyslipidemia, IFG, IGT, WCH, chronic inflammations
and infections and irreversible end points including
obesity, hypertension, DM, cirrhosis, PAD, COPD,
CRD, CAD, mesenteric ischemia, osteoporosis, and
stroke. Hypertriglyceridemia may be one of the
most significant reversible parameters of the
syndrome, and it is better to have the lowest
plasma triglyceride value as much as possible
to live longer.
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