Role of diabetes, hypertension, and cigarette smoking on atherosclerosis

Article (PDF Available)inJournal of cardiovascular disease research 1(2):64-8 · April 2010with 68 Reads
DOI: 10.4103/0975-3583.64436 · Source: PubMed
Abstract
Hyperosmolar food causes atherosclerosis. Hyperosmolal food hypothesis encompasses all the factors involved under one heading and, that is, the generation of heat in the body. The involvement of cigarette smoking is obvious. High glycemic index food and diabetes result in high levels of blood glucose, which raises the core body temperature. The ingestion of hyperosmolal salt, glucose, and amino acids singularly or synergistically raise the core body temperature, forcing abdominal aorta to form an insulation wall of fatty material causing atherosclerotic plaques. The osmolarity of food, that is glucose, salt, and amino acids is reduced when water is ingested with food. The incidence of atherosclerosis goes down with increasing intake of water.
J Cardiovasc. Dis. Res. Vol. 1 / No 2
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and increases core body temperature. This phenomenon
has been called diet-induced thermogenesis (DIT),
postalimentary hyperthermia, and thermic effect of food.
According to Jequier,
[4]
thermic response to amino acids,
glucose, and lipids are 30–40%, 6–8%, and 2–3% of
energy infused, respectively. In another study, Westerterp
[5]
showed that alcohol and protein play the biggest role in
thermogenesis. Scott and Devore
[6]
con rmed Westerterp’s
ndings by demonstrating that 100% as well as 60% protein
shakes produce higher DIT as compared with 60% fat,
30% protein, 10% carbohydrate and 60% carbohydrate,
30% protein, 10% fat, shakes. To determine the mechanism
of thermogenesis, Osaka et al.
[7-9]
infused hypertonic
solution of glucose, NaCl, fructose, and amino acids in
the intestine of urethane-anesthetized rats. A higher core
body temperature was observed with increasing amounts
of the above-mentioned nutrients. Furthermore, an
intravenous injection (IV) of these nutrients also caused
thermogenesis accompanied by an increase in plasma
osmolality. However, thermogenesis caused by IV was
lesser than that caused by the intestinal infusion of NaCl
and the solutions of the other above-mentioned nutrients,
suggesting an involvement of intestinal osmoreceptors.
This further suggests that it is unlikely that IV and intestinal
osmotic stimulation induces identical mechanisms of
INTRODUCTION
People all over the world suffer from atherosclerosis. Therefore,
etiology of the disease should be the same irrespective of
geographical location. Mathur
[1-3]
has described the effect
of hyperosmolality of food consumed in the development
of atherosclerosis. These articles state that the ingestion of
caloric-rich food containing NaCl, amino acids, and glucose
raises the core body temperature. As a result, arteries build
insulatory layers of fatty material to protect themselves
from temperature uctuations caused by thermogenesis.
Similarly, cigarette smoking raises lung temperature and leads
to fatty deposits in arteries. Consumption of fat does not
cause atherosclerosis because it does not raise core body
temperature. Fatty deposits in arteries are not the cause but the
manifestation of the disease. Furthermore, being overweight is
also not the cause of disease, it just exacerbates the condition.
In addition, diabetes mellitus causes atherosclerosis because it
causes hyperglycemia, which leads to excessive thermogenesis.
Now let us peruse the literature in the light of hyperosmolal
food hypothesis.
THERMOGENESIS
Food intake stimulates the metabolic rate of the whole body
Role of diabetes, hypertension, and cigarette smoking on
atherosclerosis
Ram K. Mathur
California Department of Public Health, 850 Marina Bay Parkway, Richmond, CA 94804, USA
Address for correspondence: Mr. Ram K. Mathur, California Department of Public Health,
850 Marina Bay Parkway, Richmond, CA 94804, USA. E-mail: RamKishoreMathur@yahoo.com
ABSTRACT
Hyperosmolar food causes atherosclerosis. Hyperosmolal food hypothesis encompasses all the factors involved
under one heading and, that is, the generation of heat in the body. The involvement of cigarette smoking is
obvious. High glycemic index food and diabetes result in high levels of blood glucose, which raises the core
body temperature. The ingestion of hyperosmolal salt, glucose, and amino acids singularly or synergistically
raise the core body temperature, forcing abdominal aorta to form an insulation wall of fatty material causing
atherosclerotic plaques. The osmolarity of food, that is glucose, salt, and amino acids is reduced when water is
ingested with food. The incidence of atherosclerosis goes down with increasing intake of water.
Key words: Atherosclerosis, cigarette smoking, diabetes, hypertension
DOI: 10.4103/0975-3583.64436
Review Article
JCDR
Available Online: www.jcdronline.org
65
J Cardiovasc. Dis. Res. Vol. 1 / No 2
thermogenesis. However, it does show that an increase in
the plasma osmolality, within the physiological range, elicits
thermogenesis. The mechanism of thermogenesis is not
clear. However, it may involve intestinal osmoreceptors.
The authors also found that food intake stimulated the
metabolic rate of the whole body and increased the core
body temperature. The core body temperature is measured
by inserting a thermister in the anus. The skin or cutaneous
body temperature is measured by a thermister taped to
the lateral surface of a rat’s tail. The mechanism of core
and skin temperatures are regulated differently.
[10,11]
It is
this thermogenesis that is responsible for the generation
of atherosclerotic plaque. Furthermore, it is only the core
body temperature that plays the main role and not the
whole body temperature or the atmospheric temperature.
In addition, there is no evidence of this disease being more
prevalent in people running high fever for a prolonged
period of time or in those living in warm to hot climates.
HYPEROSMOLAL FOOD
The ingestion or intravenous infusion of food nutrients
raises body temperature. Westerterp
[5]
stated that the
hierarchy in DIT descends from proteins to carbohydrates
to fats, which is similar to macronutrient oxidation in
postprandial state. Therefore, it seems that fat produces
the least thermic response. This was further elucidated by
Nagai et al.
[12]
They found that high fat meals had lower
thermic effects than low fat meals.
Osaka et al.
[7-9]
con rmed low thermic response of fat
by infusing 100% saf ower oil into the duodenum of
urethane-anesthetized rats. Saf ower oil did not produce
any thermic response as compared with 5–20% glucose,
2–4% NaCl, 20% fructose, and 5–10% solutions of various
amino acids. Furthermore, infusion of 0.9% NaCl or
distilled water also did not produce any heat. However,
the thermic response increased with an increase in the
osmolarity of glucose, fructose, amino acids, and NaCl
solutions. Similar effects were observed in conscious
animals and humans by Osaka and coworkers.
CONSUMPTION OF WATER
Amount of consumption of water is the single most
important factor in the development of atherosclerosis.
It can increase or decrease the osmolarity of food.
The United States Department of Agriculture (USDA)
recommends a water intake
[13]
between 1 and 1.5 mL/kcal
of energy expenditure, which translates to 2–3 L of water
per day. In the United States and other western countries,
water is consumed more in the form of beverages rather
than pure water. According to the USDA Nationwide
Food Consumption Survey
[14]
of 1977–1978, the median
intake of water as such by a person was only 662 mL/
day. In similar USDA surveys of 1994–1996 and 1998,
[15]
drinking water consumption by adult males and females
was 600 and 549 mL/day, respectively. These drinking
water consumption gures were far below the USDA
recommendations of 2–3 L/day.
Chan et al.
[16]
in a remarkable cohort study discovered a
strong negative multivariate association between the intake
of water and the risk for fatal coronary artery disease and, in
contrast, a positive association between the intake of uids
other than water and the risk for heart diseases. High intake
of water (5 or more glasses/day) compared with low intake
(2 or fewer glasses/day) were associated with a very high
relative risk of 0.46 in men and 0.59 in women. At the same
time, a high versus low intake of uids other than water
was associated with a relative risk of 1.46 in men and 2.47
in women. These statistics remained virtually unchanged in
multivariate analysis adjusted for age, education, smoking,
hypertension, body mass index, and hormone replacement
therapy (in women only). Therefore, it is pertinent to look
at the per capita consumption of uids other than water,
that is, sweetened beverages that increase the osmolality
of food and also cause hyperglycemia. According to a
survey between 1994 and 1996 conducted by Wright et
al.,
[17]
the mean consumption of soft drinks by adult males
and females in the United States were 752 and 595 mL/
day, respectively. This survey also shows that children
aged between 2 and 5 years drank on average 266 mL of
soft drink per day, which surpassed their water intake of
259 mL/day. Similarly, the consumption of soft drinks by
people of other age groups was higher than their water
intake. This may be one of the reasons for atherosclerotic
plaques appearing in children aged 2–5 years. According
to a study by Berenson et al.,
[18]
all persons in the age group
between 2 and 39 years had fatty streaks in the aorta. This
study states that the prevalence of fatty streaks in coronary
arteries increases with age from approximately 50% at
2–15 years of age to 85% at 21–39 years (P = 0.01). The
statistics are alarming because 50% of all the children in
the United States are already af icted with the disease by
the age of 15 years.
THE ROLE OF HYPERGLYCEMIA, HIGH GLYCEMIC
INDEX FOOD, AND DIABETES MELLITUS
Ingestion of high glycemic index food creates postprandial
hyperglycemia and creates physiologically a diabetic-like
Mathur: Role of diabetes, hypertension, and cigarette smoking on atherosclerosis
J Cardiovasc. Dis. Res. Vol. 1 / No 2
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condition in experimental animals.
[19]
Coutinho et al.
[20]
stated
that postprandial hyperglycemia is an important risk factor for
cardiovascular diseases not only among patients with diabetes,
but also among the general population. Dickinson and
Brand-Miller
[21]
stated that several lines of evidence indicate
that exaggerated postprandial glycemia puts individuals even
without diabetes at greater risk of developing cardiovascular
disease. Furthermore, Ceriello
[22]
and de Vegt et al.
[23]
stated
that a high 2-hour postprandial glucose was independently
associated with all-cause and cardiovascular mortality in a
population even without diabetes.
Renard et al.
[24]
stated that diabetes causes atherosclerotic
lesions regardless of diet. They also discovered that
diabetic mice had signi cantly higher cholesterol on a
cholesterol-free diet as compared with nondiabetic mice,
which could be attributed only to hyperglycemia in diabetic
mice. Therefore, this study suggests that the synthesis
of cholesterol is endogenous because it is not coming
from the diet. In another study using an animal model,
Kunjathoor et al.
[25]
showed that hyperglycemia and not
hyperinsulinemia is responsible for the development of
atherosclerosis. Therefore, both diabetes mellitus and high
glycemic index food can increase blood sugar and cause
excessive thermogenesis.
Sartippour and coworkers
[26,27]
stated that lipoprotein lipase
(LPL) produced by macrophages in vascular walls may
favor the development of atherosclerosis by promoting
lipid accumulation within the atherosclerotic lesion. They
demonstrated that high glucose concentration stimulated
in vitro murine and human microphage LPL production.
They measured macrophage LPL mRNA expression,
immunoreactive mass, and activity in normotriglyceridemic
subjects and patients with type 2 diabetes. Monocytes
isolated from healthy control subjects and patients with type
2 diabetes were differentiated into macrophages in RPMI
media containing 20% autologous serum. After culturing for
5 days in diabetic sera, macrophage LPL mRNA expression
increased signi cantly as compared with its expression in
control subjects. Differentiation of macrophages of diabetic
patients in sera obtained from control subjects signi cantly
reduced these anomalies. Conversely, culturing macrophages
of control subjects in sera of diabetic patients signi cantly
increased the LPL mass, and its activity in these cells. The
authors concluded that diabetes may contribute to the
development of atherosclerosis.
CONSUMPTION OF SODIUM CHLORIDE
A positive correlation between salt intake and cardiovascular
diseases has been known to exist for a long time. Menton
et al.
[28]
stated that epidemiologic, migration, intervention,
and genetic studies in humans and animals provide very
strong evidence of a causal link between high salt intake and
high blood pressure. Furthermore, Miura and Nakagawa
[29]
stated that a reduction in salt intake remarkably decreased
blood pressure in the elderly, the middle-aged, and the
younger generation in Japan. It is also known that obesity
and diabetes mellitus increase a patient’s risk for stroke.
The risk for atherosclerosis is even higher when a diabetic
patient has high blood pressure. The most plausible
explanation again is that both NaCl and glucose in blood
synergistically raise both osmolarity of blood and core body
temperature, resulting in atherosclerotic plaque formation.
Because hypertension is a major risk factor for
atherosclerosis, Ketonen et al.
[30]
tested whether high
salt intake would aggravate endothelial dysfunction and
promote atherosclerosis in apolipoprotein E-de cient
mice (ApoE(/) mice) and their littermate controls.
Their ndings suggest a detrimental role of high salt
(7%) intake in the development of atherosclerosis and
underscore the importance of increased oxidative stress
in the pathogenesis of salt-induced vascular damage.
Similarly, Weiss and Taylor
[31]
tested whether atherosclerosis
was increased in the setting of a low renin model of
hypertension. They observed a dramatic increase in the
atherosclerotic lesion areas in the setting of either a low- or
high-fat diet. In the hypertensive animals, they observed
an increase in angiotensin II staining that was localized to
adventitial macrophages. The increase in atherosclerosis
was inhibited by the administration of an angiotensin
receptor antagonist, an angiotensin-converting enzyme
inhibitor, or a renin inhibitor. These data suggest that even
in the setting of hypertension, which is not associated with
the activation of the systemic renin–angiotensin system,
local generation of angiotensin II within the arterial walls
may be of pathophysiological relevance to the development
of atherosclerosis.
CONSUMPTION OF PROTEINS, FATS, AND
CARBOHYDRATES
Contrary to current theories, high fat diet does not cause
atherosclerosis. It is further substantiated by French
paradox.
[32]
In France, there is a high intake of saturated
fat but low mortality from coronary heart disease. It is
high carbohydrate and high protein intake that leads to
atherosclerosis. In addition, Karst et al.
[33]
have shown
that in DIT, protein was at least 3 times as large a thermic
contributor as isocaloric carbohydrate supply. These
investigators also discovered that dietary fats produced no
Mathur: Role of diabetes, hypertension, and cigarette smoking on atherosclerosis
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J Cardiovasc. Dis. Res. Vol. 1 / No 2
evident thermic response. The doubling of energy from
either casein or hydrolyzed starch led to an approximate
doubling of thermic effect. Kurowska and Carroll
[34]
have shown that in rabbits, the elevation of cholesterol is
produced by feeding a cholesterol-free, semi-puri ed diet
containing 30% casein amino acid mixture or 14.7% casein
amino acid mixture, which corresponds to a normal level
of dietary protein. Therefore, a diet high in salt, protein,
and carbohydrate will maintain an elevated core body
temperature and lead to atherosclerosis plaque formation.
CIGARETTE SMOKING
The association between long-term cigarette smoking and
coronary artery disease is well established. Furthermore,
diabetics who smoke develop more severe cardiovascular
diseases early in life. In cigarette smoking, lungs inhale
hot smoke because at the time of puff, the temperature
at the tip of the cigarette is around 950°C.
[35]
The smoke
also carries numerous chemicals that adversely affect
the elasticity of lungs and the hot smoke raises the lung
temperature and in turn raises the core body temperature.
The lungs become incapable of performing one of their
vital physiological functions, that is, cooling or removing
the heat from the body. Karim et al.
[36]
have illustrated
that smoking is associated with subclinical atherosclerosis
in diabetics and interacts with the duration of diabetes
to accentuate atherosclerosis. The association between
carotid intima-media thickness and the duration of diabetes
increases with both the frequency and duration of smoking.
The examination of the Framingham Heart Study by Wolf
et al.
[37]
revealed that regardless of smoking status and sex,
hypertensive subjects had twice the incidence of stroke.
Furthermore, smoking was determined to be a signi cant
independent contributor to risk of stroke generally and
brain infraction speci cally. This study also revealed that
the risk of stroke increased with the number of cigarettes
smoked. The report further states that after cessation of
cigarette smoking, the risk signi cantly dropped in 2 years
and was at the level of nonsmokers in 5 years. This study
suggests that the harmful effect of smoking is reversible
as far as the stroke is concerned.
TEST OF HYPEROSMOLAL FOOD HYPOTHESIS
Okinawa centenarians
[38]
come closest to getting a perfect
score on hyperosmolal food hypothesis test. Okinawa
centenarians consume food that has very high water
content, such as cereals, roots, beans, sh, vegetables, and
others. Their beverage is mainly tea, which is close to 99%
water. However, they consume about 4 g of NaCl per day,
which is too high. In spite of this, they are least affected
by cardiovascular diseases as compared with the rest of
the world.
CONCLUSION
It is well known that diabetes, excessive salt intake,
obesity, and a host of other factors lead to atherosclerosis.
However, till now no general theory existed that could
explain the involvement of all the above factors in the
development of atherosclerosis, but now hyperosmolal
food hypothesis explains the etiology of the disease
remarkably well. Thus, only this hypothesis can explain
the development of atherosclerosis all over the world.
The details of hyperosmolal food hypothesis have been
described elsewhere.
[1]
FUTURE PERSPECTIVE
In perspective, research on atherosclerosis currently is in
disarray. The scientists require a paradigm shift in their
thinking. We already know that fat intake does not cause
atherosclerosis. Lowering blood cholesterol level does not
protect people from becoming a prey to the disease. People
on low fat diet are also not spared from the disease because
the human body is capable of synthesizing cholesterol if
needed by the body for insulation from heat. Thus, they
too get heart attacks anyway. Furthermore, patients after
coronary artery bypass graft (CABG) surgery relapse 50%
of the time because the atherosclerotic plaque continues
to build up in the grafted arteries and elsewhere. Patients
are advised to stay away from fatty foods, which obviously
does not help because fatty meal is not the cause for
atherosclerosis. Therefore, the researchers should rst
examine the cause of the disease before trying to cure it;
otherwise, we will be treating symptoms rather than curing
the disease itself. Likewise, research foundations should
increase funding on causal analyses and reduce nancial
grants on nding cures at this time.
However, there is some good news. The rate of
cardiovascular diseases is slowing down, but it is not
because of statins or CABG surgery. It is because of the
advent of bottled mineral water. Luckily, it has become
fashionable to carry a bottle of mineral water anywhere
you go. It is this water consumption, which is diluting the
hyperosmolar foods we eat.
Finally, this field requires some broad theories and
hypotheses explaining the involvement of foods, diabetes,
hypertension, cigarette smoking, and others in the
Mathur: Role of diabetes, hypertension, and cigarette smoking on atherosclerosis
J Cardiovasc. Dis. Res. Vol. 1 / No 2
68
Available Online: www.jcdronline.org
formation of atherosclerotic plaque. We have a mission
but are lacking the vision. That is why we have not made
any progress even though we have worked on it for more
than 50 years.
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Mathur: Role of diabetes, hypertension, and cigarette smoking on atherosclerosis
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    From the beginning of Nina Teicholz's article: "... why does the expert advice underpinning US government dietary guidelines not take account of all the relevant scientific evidence?" Good question, but my question is better: Why are fully ignored the fundamentals and principles of biology, biochemistry, nutrition and health sciences? Nina Teicholz has right, but her criticism isn't strong enough. The reality is darker. Without true science of salt, all the nutrition science is a big heap of junk – including DGA 2015. The real scientific evidences (fundamentals) are totally ignored. We eat, because we need energy. We adopted only the natural mineral content of foods, but no the added sodium salts. The salt is the greatest blunder of the Homo sapiens. Sodium content of extracellular fluids (blood and lymph) is about 140 mmol/l, but in our cells is only around 10 mmol/l (and must be within a narrow range). The continuous diffusion of sodium ions into the cells = the necessary and ordered circumstance decline. This means - the entropy (the disorder) is growing. Our cells needs continuous energy expenditure against spontaneous diffusion by continuous work of the sodium/potassium pumps (needs and expends energy of ATP molecules). "The activity of Na-K pump has been estimated to account for 20-40 % of the resting energy expenditure in a typical adult." [1] This is a significant part of our total energy expenditure (even in a breast-feed infant), and the expended (squandered!) energy depends on unnecessary sodium intakes. This is the most dangerous wasting of the humanity. The sodium intake above the optimum generates a cascade of unhealthy consequences. We cannot adopt the salted foods. The growing entropy is our fiercest enemy, and the salt is his perfect food. We squander the energy against excess diffusion and excess entropy, in our cells. The real science of salt is a taboo, but this is a fatal error because craziness or villainy to increase the water level deliberately - on an area hit with flood. The essence of the true science of salt is so simple - a kindergartener may understand it. But at least in the past 50 years the "health science" - worked on it - let nobody understand it. This work is very successful, the global ignorance is frightening.
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    Aims: Atherosclerosis is an inflammatory process with different cardiovascular risk factors (CVRFs) contributing to its pathogenesis. We aimed to evaluate the specific relationship between circulating blood leukocytes, troponin I and CVRFs. Methods: We prospectively enrolled 959 patients with evidence of acute coronary syndrome either in form of unstable angina or STEMI or NSTEMI. Details demographic characteristics, CVRF and biochemical parameters such as total white blood cells (WBC), neutrophil, lymphocytes, platelet, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and troponin I were collected. Results: The results indicated that patients having either hypertension, diabetes or smoking habit had significantly higher levels of total WBC (p=0.013), neutrophil (p=0.029), NLR (p=0.029) and PLR (p=0.009). The level of troponin I was unaffected by these risk factors. Significant association of hypertension was found with total WBC (p=0.0392), lymphocytes (p=0.0384) and PLR (p=0.0027), whereas in diabetes and females all other leukocyte subtypes were significantly altered except for platelet and troponin I. Smokers had higher level of total WBC count (p=0.0033) and PLR (p=0.0464). No relationship between CVRFs and leukocytes was observed in males. The age independent effect was observed with PLR, whereas association with total WBC, lymphocytes, NLR, platelet was specific in older population. In younger patients NLR (p=0.0453) is more likely to be elevated. Mortality was significantly associated with changes in the leukocytes but not with the CVRF presence. Conclusion: We demonstrate that the neutrophils, lymphocytes and total WBC along with its ratios predict mortality and are more likely to be elevated in presence of CVRFs.
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    Objective: Some of the factors affecting serum osmolality are also known risk factors for coronary artery disease. In the present study, we aimed to investigate if there is a relationship between serum osmolality and a history of coronary artery disease. Methods: The present study was designed as a case control study. We selected 141 patients aged 45 years or over with consecutive sampling method. Of these, 61 patients had a history of coronary artery disease. In the study group, coronary artery disease was documented and the patients have been under medication for this specific illness. Serum osmolality was calculated using appropriate formula. Results: Estimated serum osmolality (t= -4.209, p=0.000), fasting plasma glucose (t= -2,606, p = 0.01) and waist to hip ratio (t= -2,193, p=0.03) were higher in patients with coronary artery disease. Conclusion: We have shown that estimated serum osmolality correlates with a history of coronary artery disease.
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    Cardiovascular disease (CVD) has remained a leading cause of death worldwide for the past several decades. It is a progressive pathological condition which gradually develops during the course of one’s life at a rate which depends on the extent of interplay between its unmodifiable and modifiable risk factors. Its genesis lies in the initiation of atherosclerosis, which may remain asymptomatic in the subclinical state. Its gradual progression culminates in symptomatic CVD and its onset invariably predicts an adverse prognosis leading to multiple recurrent cardiac upheavals if uncontrolled. At this stage, clinicians largely rely on routine diagnostic procedures and physical examination for arriving at therapeutic decisions on patient management. Such evaluations are however bound by limitations, especially with irreversible changes having already set in at molecular and cellular levels, thus largely leading to ineffective treatment. Logically, disease management can be considered successful if undertaken before the onset of overt clinical manifestations which may conclusively require presymptomatic prognostication of the pathological condition. Biomarkers, in this regard, are gaining increasing interest, as they are, to some extent able to identify high risk subjects and predict the future development of CVD in them. Further, it is also interesting to note that ethnicity plays a very important role in determining the extent to which these markers can be implica ted in cardiovascular risk prediction in specific populations. This is particularly true in case of Asian Indian populations wherein biomarkers, established for the Western population, are not so significant and certain other markers which are considered of low priority in Caucasians assume significance. This review focuses on different biochemical and immunological parameters, some of which have already been well established as biomarkers and routinely considered by clinicians for risk assessment. Certain additional novel parameters, which are slowly gaining importance as disease causal and consequential agents and throwing throw light on the progress of the disease are also highlighted.
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  • Article
    In most countries, high intake of saturated fat is positively related to high mortality from coronary heart disease (CHD). However, the situation in France is paradoxical in that there is high intake of saturated fat but low mortality from CHD. This paradox may be attributable in part to high wine consumption. Epidemiological studies indicate that consumption of alcohol at the level of intake in France (20-30 g per day) can reduce risk of CHD by at least 40%. Alcohol is believed to protect from CHD by preventing atherosclerosis through the action of high-density-lipoprotein cholesterol, but serum concentrations of this factor are no higher in France than in other countries. Re-examination of previous results suggests that, in the main, moderate alcohol intake does not prevent CHD through an effect on atherosclerosis, but rather through a haemostatic mechanism. Data from Caerphilly, Wales, show that platelet aggregation, which is related to CHD, is inhibited significantly by alcohol at levels of intake associated with reduced risk of CHD. Inhibition of platelet reactivity by wine (alcohol) may be one explanation for protection from CHD in France, since pilot studies have shown that platelet reactivity is lower in France than in Scotland.
  • Article
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    In adults, cardiovascular risk factors reinforce each other in their effect on cardiovascular events. However, information is scant on the relation of multiple risk factors to the extent of asymptomatic atherosclerosis in young people. We performed autopsies on 204 young persons 2 to 39 years of age, who had died from various causes, principally trauma. Data on antemortem risk factors were available for 93 of these persons, who were the focus of this study. We correlated risk factors with the extent of atherosclerosis in the aorta and coronary arteries. The extent of fatty streaks and fibrous plaques in the aorta and coronary arteries increased with age. The association between fatty streaks and fibrous plaques was much stronger in the coronary arteries (r=0.60, P<0.001) than in the aorta (r=0.23, P=0.03). Among the cardiovascular risk factors, body-mass index, systolic and diastolic blood pressure, and serum concentrations of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, as a group, were strongly associated with the extent of lesions in the aorta and coronary arteries (canonical correlation [a measure of the association between groups of variables]: r=0.70; P<0.001). In addition, cigarette smoking increased the percentage of the intimal surface involved with fibrous plaques in the aorta (1.22 percent in smokers vs. 0.12 percent in nonsmokers, P=0.02) and fatty streaks in the coronary vessels (8.27 percent vs. 2.89 percent, P=0.04). The effect of multiple risk factors on the extent of atherosclerosis was quite evident. Subjects with 0, 1, 2, and 3 or 4 risk factors had, respectively, 19.1 percent, 30.3 percent, 37.9 percent, and 35.0 percent of the intimal surface covered with fatty streaks in the aorta (P for trend=0.01). The comparable figures for the coronary arteries were 1.3 percent, 2.5 percent, 7.9 percent, and 11.0 percent, respectively, for fatty streaks (P for trend=0.01) and 0.6 percent, 0.7 percent, 2.4 percent, and 7.2 percent for collagenous fibrous plaques (P for trend=0.003). These findings indicate that as the number of cardiovascular risk factors increases, so does the severity of asymptomatic coronary and aortic atherosclerosis in young people.
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    Cardiovascular diseases are the leading cause of morbidity and mortality in diabetes. Lipoprotein lipase (LPL), a major secretory product of macrophages, has been suggested to play a key role in the development of atherosclerosis. In the present study, we evaluated the effect of high glucose on macrophage LPL mRNA expression and secretion. Exposure of murine J774 macrophages to high D-glucose concentrations (20-30 mmol/l) resulted in a dramatic upregulation of LPL mRNA expression and immunoreactive mass. This effect was not observed when these cells were incubated in the presence of L-glucose or mannitol. High glucose concentrations were also found to enhance LPL gene expression and immunoreactive mass in human monocyte-derived macrophages. J774 cells cultured in a high glucose environment expressed increased c-fos mRNA levels. Treatment of these cells with c-fos antisense DNA or protein kinase C inhibitor inhibited the stimulatory effect of glucose on LPL mRNA expression. In J774 cells exposed to high glucose concentrations, enhanced nuclear protein binding to the AP-1-responsive region of the murine LPL promoter was observed, while LPL mRNA stability remained unchanged. Overall, these results demonstrate that high glucose upregulates macrophage LPL gene expression and immunoreactive mass and that this effect involves transcriptional events.
  • Article
    In most countries, high intake of saturated fat is positively related to high mortality from coronary heart disease (CHD). However, the situation in France is paradoxical in that there is high intake of saturated fat but low mortality from CHD. This paradox may be attributable in part to high wine consumption. Epidemiological studies indicate that consumption of alcohol at the level of intake in France (20-30 g per day) can reduce risk of CHD by at least 40%. Alcohol is believed to protect from CHD by preventing atherosclerosis through the action of high-density-lipoprotein cholesterol, but serum concentrations of this factor are no higher in France than in other countries. Re-examination of previous results suggests that, in the main, moderate alcohol intake does not prevent CHD through an effect on atherosclerosis, but rather through a haemostatic mechanism. Data from Caerphilly, Wales, show that platelet aggregation, which is related to CHD, is inhibited significantly by alcohol at levels of intake associated with reduced risk of CHD. Inhibition of platelet reactivity by wine (alcohol) may be one explanation for protection from CHD in France, since pilot studies have shown that platelet reactivity is lower in France than in Scotland.
  • Article
    The impact of cigarette smoking on stroke incidence was assessed in the Framingham Heart Study cohort of 4255 men and women who were aged 36 to 68 years and free of stroke and transient ischemic attacks. During 26 years of follow-up, 459 strokes occurred. Regardless of smoking status and in each sex, hypertensive subjects had twice the incidence of stroke. Using the Cox proportional hazard regression method, smoking was significantly related to stroke after age and hypertension were taken into account. Even after pertinent cardiovascular disease risk factors were added to the Cox model, cigarette smoking continued to make a significant independent contribution to the risk of stroke generally and brain infarction specifically. The risk of stroke increased as the number of cigarettes smoked increased. The relative risk of stroke in heavy smokers (>40 cigarettes per day) was twice that of light smokers (fewer than ten cigarettes per day). Lapsed smokers developed stroke at the same level as nonsmokers soon after stopping. Stroke risk decreased significantly by two years and was at the level of nonsmokers by five years after cessation of cigarette smoking. (JAMA 1988;259:1025-1029)
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    Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety. In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.
  • Article
    After ingestion or intravenous infusion of a nutrient, the energy expenditure increases. This nutrient-induced thermogenesis represents 6 to 8% of the energy infused when glucose is infused with insulin (glucose clamp technique) to healthy subjects. At physiological plasma insulin levels (i.e. below 200 microU/ml), glucose induced thermogenesis (GIT) was 6%, whereas at supraphysiological levels (i.e. greater than 400 microU/ml) GIT was 8% of the energy content of glucose infused. This thermogenic response to glucose infusion includes two components: An "obligatory thermogenesis" which accounts for the energy cost of storing the nutrient and a "facultative thermogenesis" which is mainly due to a stimulation of sympathetic activity. The thermogenic response to lipid infusion (Intralipid 20%) was 2 to 3% of the energy infused. The stimulation of energy expenditure following amino acid infusion has been studied less in healthy subjects; in depleted patients, the thermogenic response to amino acids has been evaluated to correspond to about 30 to 40% of the amino acid energy infused. In addition to the concept of the thermogenic response to nutrients, it is of interest to know the cost of nutrient storage; for glucose, it amounted to 12%, for lipid to 4% of the energy stored. It is concluded, that lipid induces a lower thermogenic response and has a smaller cost for storage than glucose. Thus, lipid infusion allows giving energy more efficiently to the patient than large amounts of glucose. In total parenteral nutrition, it is common practice to supply non-protein energy roughly equally between glucose and fat; this is more economical than the infusion of large amounts of glucose.
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    The diet-induced thermogenesis of 12 healthy males of normal body weight was measured by means of indirect calorimetry over 6 h after test meals of 1, 2 or 4 MJ protein (white egg, gelatin, casein), carbohydrate (starch, hydrolyzed starch) or fat (sunflower oil, butter). The totals of the thermic responses proved to be dependent on the type of nutrient supplied as much as on its quantity. The effect of 1 MJ protein was at least three times as large as that of an isocaloric carbohydrate supply. The investigated dietary fats produced no evident thermic response. The doubling of the energy intake of either casein or hydrolyzed starch led to the approximate doubling of the thermic effect.