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TRANSCRIPT
UNIVERSITY OF MEDICINE AND PHARMACY OF CRAIOVA
Appreciation efficacy and safety of statin therapy in lowering cardiovascular risk in patients with type 2 diabetes, according to serum levels of inflammatory biomarkers
PhD Thesis Abstract
Key words: atorvastatin, diabetes type 2, high sensitive C-reactive protein, oxidised LDL, cardiovascular disease
Scientific Supervisor, Dr. POPESCU FLORICA PhD
PhD student, IONICĂ FLORIANA ELVIRA
Craiova
2010
1
CONTENTS
1. THE CURRENT STATE OF KNOWLEDGE ON STATINS, THERAPEUTIC SOLUTIONS IN THE DYSLIPIDAEMIA OF TYPE 2 DIABETES. .......................... 2
1.1. Diabetes and cardiovascular risk ............................................................. 2 1.1.1. LDL oxidation and oxidative stress ........................................................... 3
1.1.2. LDL oxidation and association with atherosclerosis and diabetes........ 3
1.1.3. Conclusions and perspectives .................................................................. 4
1.2. Inflammatory biomarkers predictive of acute cardiovascular events ....... 5 1.2.1. C-reactive protein (CRP) and cardiovascular risk in type 2 diabetes......... 5 1.2.2. CRP - predictor of cardiovascular events .................................................. 6 1.2.3. C-reactive protein and type 2 diabetes...................................................... 6 1.2.4. Conclusions and perspectives................................................................... 7
1.3. Lipid and non-lipid effects of statins in the prevention of cardiovascular pathology............................................................................................................... 7
1.3.1. Statin-brief history, definition, mechanisms of action................................. 7 1.3.2. Statins and diabetes.................................................................................. 8
2. OWN CONTRIBUTIONS .................................................................................... 8
2.1. Motivating the study and current working hypothesis............................... 8
2.2. Study Objectives............................................................................................ 9
4. RESULTS ......................................................................................................... 10
4.1. Demographic and clinical-biological characteristics of patients with type 2 diabetes study group....................................................................................... 10
4.1.1. Demographic characteristics of patients.................................................. 10 4.1.2. Clinical and biological characteristics of patients with type 2 DM without manifest cardiovascular disease (subgroups A1 and A2).................................. 11 4.1.3. Clinical and biological characteristics of patients with type 2 DM with acute cardiovascular events (B1 and B2).................................................................... 12
5. DISCUSSION.................................................................................................... 13
6. CONCLUSION.................................................................................................. 14
SELECTIVE BIBLIOGRAPHY.............................................................................. 17
CURRICULUM VITAE .......................................................................................... 21
2
1. The current state of knowledge on statins, therapeutic solutions in the dyslipidaemia of type 2 diabetes.
1.1. Diabetes and cardiovascular risk
In type 2 diabetes mellitus (DM 2) leading cause of mortality is
generated by the clinical consequences of atherosclerosis. LDL
cholesterol and atherosclerosis are related both to the healthy people
and those with diabetes, only those with DM 2 predisposition for
atheromatosis is higher, although their levels of LDL are similar to
those of healthy people. Atherosclerosis begins with endothelial
dysfunction, lipid accumulation in macrophages and an inflammatory
response, leading to plaque formation and narrowing of the vascular
lumen. Less resistant plates will crack and could lead to myocardial
infarction (MI) or stroke. Atherosclerotic cardiovascular disease is the
leading cause of morbidity and mortality in patients with type2 diabetes,
and the risk of developing the disease is two to four times higher than
in non-diabetic subjects [1]. In addition, the risk of cardiac morbidity
and mortality in individuals with type 2 diabetes without previous MI
has been shown to be similar to that in non-diabetic subjects with a
history of MI [1]. Several prospective studies have shown that cross a
preponderance of small LDL particles is associated with an increased
risk of coronary artery disease (CAD) and Diabetes Atherosclerosis
Intervention Study (DAIS, 2003) reported that small LDL particles are
significantly associated with progression of the disease [2].
LDL particle size can be used with LDL cholesterol determination,
to give an indication of the number of circulating LDL particles. Two
3
individuals may have the same concentration of LDL-cholesterol, but
that with predominantly small LDL particles will need more particles to
carry the same amount of cholesterol.
The observation that diabetics have small particles of LDL but
normal plasma levels of LDL-cholesterol, shows that particle number is
increased in type 2 DM.
1.1.1. LDL oxidation and oxidative stress LDL oxidation initiates a series of events that ultimately will lead
to increased acquisition of LDL by macrophages, the formation of
foamy cells and the development board aterom [3]. Oxidized LDL and
antibodies against the modified form of the lipoproteins were found in
atherosclerotic lesions [4], but not in normal arteries or veins. Some
characteristics of oxidized LDL play a role in the development of
atherosclerotic plaques: oxidised LDL is toxic for endothelial cells [5],
recruits lymphocytes in atherosclerotic lesions [6] and promotes
proliferation of macrophages within plaques [7].
1.1.2. LDL oxidation and association with atherosclerosis and diabetes
Small and dense LDL particles are considered more prone to
oxidation than large ones and at least three studies have shown an
inverse relationship between lag phase of LDL oxidation and LDL
density [10]. Using LDL split, these studies show that small and dense
LDL particles are less resistant to in vitro oxidation than large LDL
particles, energetic harvested from the same individual.
Plasma levels of oxidized LDL, measured by ELISA-sandwich
were increased in individuals with impaired glucose tolerance (TAG)
compared with control subjects after adjusting for age and body mass
4
index (BMI), and increased in patients with type 2 DM with
macroalbuminuria than in those with normo-or microalbuminuria and
healthy subjects [13]. Patients with well controlled DM have increased
plasma levels of oxidized LDL compared with control subjects, when
adjusted for LDL-cholesterol concentration [15, 16]. Moreover, it was
observed an inverse relationship between circulating levels of LDL and
oxidised LDL particle size in patients with DM 2 [16]. The middle-aged
men observed an independent association between serum oxidised
LDL and subclinical atherosclerosis assessed by intimate-media
thickness at common carotid artery [14].
1.1.3. Conclusions and perspectives There is evidence of increasingly numerous, showing that
changes in LDL increase aterogenitatea. Since the modified LDL is not
a homogeneous entity, no single diagnostic marker that adequately
reflect the risk of cardiovascular disease associated with modified LDL.
The presence in plasma of small dense LDL particles is
associated with hypertriglyceridaemia and an increased risk of
coronary artery disease (CAD). Small LDL particles predominate in
patients with insulin resistance and an inverse relationship has been
observed between LDL particle size and circulating oxidised LDL
particle number in patients with type 2 diabetes [16]. LDL particle size
may be influenced favorably by establishing a strong control of blood
glucose [17]. This supports the importance of glycemic control benefits
above and beyond established microvascular disease. LDL particle
size is increased fenofibrat [2], while therapy with statins, although
significantly reduce the total level of LDL cholesterol, not affecting
5
their size [18].
In conclusion, LDL cholesterol is a poor predictive factor for CAD
risk assessment associated with DM 2. Some oxidative and non-
oxidative modification of LDL, as oxidation and glycation contributes to
accelerating atherosclerosis in diabetes. Measuring these changes in
LDL is very technically demanding and therefore unsuitable for routine
practice. Serum triglycerides are closely related to the predominance
of small LDL particles and increased levels of oxidised LDL. In addition,
the number of LDL particles is positively correlated with risk of CAD.
1.2. Inflammatory biomarkers predictive of acute cardiovascular events
1.2.1. C-reactive protein (CRP) and cardiovascular risk in type 2 diabetes
Development high-sensitive CRP (hs-CRP) by a stable and
cheaper method, increased ability to obtain more useful determinations
of circulating levels of this cytokine and therefore redefine the
assessment of cardiovascular risk, particularly those where the risk is
intermediate, as individuals with medium LDL-cholesterol levels.
CRP is considered to be an important inflammatory cytokine,
which acts as a nonspecific defense mechanism in response to
permanent damage or infection tissue. Synthesized primarily in the
liver, CRP activity is stimulated by other cytokines, particularly
interleukin IL-6, IL-1β and tumor necrosis factor-α (TNF-α). CRP binds
to a variety of other molecules, particularly liposomes and lipoproteins,
the LDL and VLDL cholesterol and is a potent activator of classical
complement pathway. The data accumulated suggest that CRP, which
6
Some data [26], reinforcing the concept that inflammation plays
an important role in the pathogenesis of type 2 diabetes and linking
diabetes with concomitant states there is an inflammatory component
[27]. There is evidence that insulin resistance with normal glycemia is
an proinflammatory state and there with long before the actual onset of
type 2 diabetes [28]. The mechanism has a major role in the
inflammatory cascade of events leading to rupture aterom plate. Up-
regulation of receptor for advanced glycation and products (AGES)
was associated with increased inflammatory reactions. Increased
expression of these receptors was correlated with poor control of
blood glucose and could contribute to the area of complex
is also found in macrophages from the ateroma plaque is associated
atherothrombosis as concerned or mechanism.
1.2.2. CRP - predictor of cardiovascular events
Moderate increases in CRP can be found even in apparently
healthy people [6]. A progressive increase of CRP may reflect vascular
inflammation amplification stages, but specific clinical conditions in
which the event is not fully understood. Although LDL cholesterol
remains a major risk factor for cardiovascular disease, at least one
third of coronary events occur in individuals with an LDL level below
130 mg/dl [25], which is generally considered a medium level in
individuals without known coronary artery disease. Monitoring levels of
CRP in these clinical conditions can be very useful for risk assessment.
Evidence that CRP levels are elevated during cardiovascular and
cerebrovascular events suggests that CRP is valuable in predicting the
subsequent evolution of these events.
1.2.3. C-reactive protein and type 2 diabetes
7
mechanisms that lead to acceleration of atherosclerosis in patients
with diabetes [29].
1.2.4. Conclusions and perspectives
Current Opinions differ regarding the value of CRP test additive,
in addition to classical risk factors for cardiovascular risk assessment.
Continue discussion on the use of CRP as part of screening for global
risk assessment.
1.3. Lipid and non-lipid effects of statins in the prevention of cardiovascular pathology
1.3.1. Statin-brief history, definition, mechanisms of action
First clinical experience of administration of statins was held in
1976, and since the 80 trials were initiated extensive research of the
effects of statins in U.S. clinics. The emergence of 3-hydroxy-3
inhibitors -metilglutaril-coenzyme A reductase inhibitors (statins) has
revolutionized treatment of hypercholesterolemia. In the liver, statins
specifically inhibit competitive, reversible HMG-CoA reductase, the
enzyme that catalyzes the conversion of HMG-CoA (hydroxymethyl-
glutaryl coenzyme A) to mevalonic acid, limiting stage the formation of
cholesterol [37]. By decrease in cholesterol synthesis, statins also
reduce, the formation of lipoproteins, especially LDL and VLDL.
Because diabetes is considered equivalent for heart disease,
aggressive treatment of dyslipidemia (especially when using statins) to
reduce coronary risk, is a priority in the care of diabetic patients.
Observations of large-scale randomized clinical trials underlying of
recommendations of international guidelines that support the need and
importance of reaching lipid targets all people with diabetes. Lipid
8
control is part of multifactorial management of diabetes, which should
be early and intensive.
1.3.2. Statins and diabetes
Endothelial dysfunction is representative of the DM and insulin
resistance and is characterized by reduction effective action of nitric
oxide. Hyperglycemia status implies a cascade of mechanisms leading
to increased vascular tone. In patients with DM statins improve
endothelial dysfunction by stimulating NO production by endothelial
cells, modulating the release and action vasoconstrictors.
2. Own contributions
2.1. Motivating the study and current working hypothesis Is well studied many effects of statins: lipid-lowering, anti-
inflammatory, antiproliferative, antioxidant, immunosuppressive,
positive influence on rheological parameters and thrombogenesys,
correction of endothelial function. These effects have been well studied
in patients with ischemic heart disease and less in patients with type 2
diabetes. How atherosclerosis is a diffuse process, serum biomarkers
have the potential to provide a general measure of risk that can allow a
more targeted, with a variety of techniques focused on those with
abnormal levels. In addition, they can provide an overall assessment of
treatment response to various interventions. Serum biomarkers are
likely to play an important role in the future, risk stratification and
prognosis of cardiovascular disease, especially when established risk
factors are complementary. Compared to invasive or noninvasive
procedures, their evaluation has the advantage of being relatively free
9
of risks, less expensive, and applicable to a wide range of populations
at risk.
Although it was shown that treatment with statins reduce CRP
levels in a manner that is largely independent of LDL cholesterol level,
lack of evidence linking a greater reduction in CRP levels by reducing
the rate of cardiovascular events.
Provocative information now suggests that hsCRP is useful in
monitoring the effectiveness of statins in primary prevention, after the
stent implantation, and in increased risk of acute coronary syndromes.
Applying biology of inflammation in atherosclerosis has already
provided a new perspective on how current interventions, both
pharmacological and in lifestyle can reduce cardiovascular risk. There
are no studies that examine various lipid or non-lipid effects of statins,
according to the dose administered to prevent acute cardiovascular
events (especially the influence of hs-CRP and oxidized LDL) in
patients with type 2 diabetes with or without dyslipidemia or who
suffered a heart attack or stroke.
There is data showing the association between blood levels of
hs-CRP and LDL-ox, and that would be predictive value for the
cardiovascular risk of the two biomarkers together, in diabetic patients.
2.2. Study Objectives 1. Evaluation of inflammatory biomarkers (hs-CRP), of oxidative
stress (oxidized LDL), lipids (cholesterol, triglycerides), blood glucose
(blood sugar, HbA1c) and hepato-renal (ALT, AST, microalbuminuria)
in patients with diabetes tip2.
2. Setting changes inflammatory biomarkers (hs-CRP), oxidised
LDL, the metabolism of blood glucose and lipid parameters between
10
The study included 84 patients with type 2 diabetes, of whom 43
patients without acute cardiovascular events (group A) and 41
patients with type 2 diabetes without manifest cardiovascular disease
and those with heart attack or stroke.
3. The changes that inflammatory biomarkers (hs-CRP), oxidised
LDL, the metabolism of blood glucose and lipid parameters in patients
untreated with lipid-lowering drugs and patients treated with
atorvastatin.
4. Analysis of lipid parameters, the hs-CRP and oxidised LDL in
the treatment of long (12-24 weeks) with atorvastatin versus short-term
treatment (4-8 weeks).
5. Assessing the influence of long-term therapy (12-24 weeks)
with atorvastatin on glycemic metabolism parameters versus short-
term treatment (4-8 weeks).
6. Comparison of atorvastatin action, depending on dose, the
values of hs-CRP, oxidized LDL and lipoproteins in patients with acute
cardiovascular events.
7. Comparison of atorvastatin action, depending on dose, the
values of hs-CRP, oxidized LDL, lipoproteins in patients without
manifest cardiovascular disease.
8. Highlighting the type and dynamics of adverse reactions,
depending on the dose of atorvastatin administered and diabetic
features.
4. Results
4.1. Demographic and clinical-biological characteristics of patients with type 2 diabetes study group
4.1.1. Demographic characteristics of patients
11
patients with acute cardiovascular events (group B). In each of the two
study groups were distinguished two subgroups: patients who not
received lipid-lowering medication (A1, B1) and patients treated with
atorvastatin (A2, B2).
Diagnosis of type 2 diabetes was based on historical data,
clinical and laboratory explorations. The absence of cardiovascular
disease was defined as documented absence of myocardial infarction,
stroke or peripheral arterial disease. Retinopathy and nephropathy
have been refuted by practitioners.
The average age of patients included in the study was 61.12 ±
11.38 years (age limits - 39 and 84 years), with significant difference
between the two groups: the group A (without acute cardiovascular
events) mean age was 53.61 ± 6.68 years and in group B (acute
cardiovascular events) mean age was 69.88 ± 9.27 years. The gender
distribution showed a predominance of women in group A vs. 61.9%.
38.1% and a high proportion of men in group B 72.22% vs.. 27.78%.
4.1.2. Clinical and biological characteristics of patients with type 2 DM without manifest cardiovascular disease (subgroups A1 and A2)
Table 1. Characteristics of patients with type 2 DM without manifest CVD.
Characteristics
A1F A1B A1T A2F A2B A2T
Glucose [mg/dl]
143,22 +-21,75
156,25 +-24,22
147,23 +-22,39
136,750 +-12,72
132 +-13,70
134,37 +-8,89
HbA1c [%]
6,45 +-0,39
6,75 +-0,43
6,54 +-0,41
6,77 +-0,26
6,59 +-0,42
6,68 +-0,25
Col. total [mg/dl]
255,66 +-28,77
234,25 +-56,80
249,07 +-38,26
204,25 +-2,82
199,255 +-35,33
201,750 +-11,88
LDL col [mg/dl]
133,95 +-25,87
99,47 +-39,49
123,34 +-33,32
90,65 +-4,80
88,4 +-31,80
89,520 +-12,34
HDL col [mg/dl]
34,71 +-2,10
33,75 +-2,79
34,41 +-2,26
38,9 +-0,42
37,65 +-1,45
38,27 +-2,17
Triglycerides [mg/dl]
189,77 +-30,44
220,5 +-46,11
199,23 +-36,97
163 +-0,42
159,75 +-17,11
161,37 +-9,92
ALT [U/l]
22 +-5,40
23,75 +-5,31
22,53 +-5,22
41 +-3,53
37,5 +-6,49
39,25 +-3,15
AST [U/l]
25,11 +-6,95
22,75 +-10,24
24,38 +-7,73
45,75 +-7,07
43,5 +-6,22
44,62 +-3,42
oxLDL [U/l]
86,78 +-8,99
89,69 +-19,54
87,67 +-12,30
61,52 +-1,41
64,21 +-6,63
62,86 +-8,11
hs-CRP [mg/l]
6,48 +-3,65
8,7 +-4,17
7,16 +-3,79
1,05 +-1,37
1,77 +-1,61
1,41 +-0,64
BMI [kg/m2]
28,23 +-2,85
27,42 +_1,69
27,98 +-2,51
27,9 +-2,12
29,25 +-1,88
28,57 +-2,39
DM age [months]
31,44 +-41,14
33,06 +- 44,26
32,92 +-43,04
56,33 +- 74,32
60,41 +- 79,14
58,37 +-77,01
Note: CVD = cardiovascular disease, A1 = subgroup without manifest CVD untreated with ATV, A2 = subgroup without manifest CVD treated with ATV, F = female, M = male, T = total.
4.1.3. Clinical and biological characteristics of patients with type 2 DM with acute cardiovascular events (B1 and B2)
Subgroup B included 41 patients who suffered an acute
myocardial infarction (AMI) or stroke (AVC) at inclusion in study group.
The median age group was 69.88 ± 9.56 years and the distribution by
sex showed a predominance of men 72.22% vs. 27.78%. Table 2. Characteristics of patients with type 2 DM with acute
cardiovascular events.
12
Characteristics
B1F B1B B1T B2F B2B B2T
Glucose [mg/dl]
163,00 +-11,38
166,12 +-6,32
165,5 +-12,87
148 +-10,14
179,60 +-21,73
167,75 +-23,80
HbA1c 7,29 7,43 7,4 6,91 7,94 7,55
13
Note: CVE = cardiovascular events, B1 = subgroup with acute CVE untreated with ATV, B2 = subgroup with acute CVE treated with ATV, F = female, M = male, T = total, ATV = atorvastatin.
5. Discussion
[%]
+-0,30 +-0,20 +-0,39 +-0,33 +-0,75 +-0,80
Col. total [mg/dl]
270 +-9,17
211,25 +-15,12
223 +-39,81
203,33 +-7,57
196,80 +-15,72
199,25 +-13,00
LDL col [mg/dl]
163,600 +-11,52
107,85 +-14,81
119 +-36,63
88,27 +-7,91
80,28 +-19,27
83,27 +-15,72
HDL col [mg/dl]
32,3 +-0,53
32,86 +-3,12
32,75 +-1,30
38,83 +-2,66
36,68 +-1,78
37,49 +-2,25
Triglycerides [mg/dl]
161,5 +-13,21
154 +-6,94
155,500 +-15,46
166,33 +-3,78
174,200 +-16,67
171,25 +-13,40
ALT [U/l]
37 +-3,36
27,87 +-1,91
29,7 +-7,28
38,33 +-6,50
31,4 +-5,59
34 +-6,54
AST [U/l]
38 +-2,98
33,87 +-3,87
34,7 +-5,77
44,66 +-4,04
38,8 +-5,49
41 +-5,58
oxLDL [U/l]
93,22 +-11,84
90,17 +-2,94
90,78 +-6,00
72,17 +-4,98
63,26 +-3,41
66,6 +-5,91
hs-CRP [mg/l]
10,7 +-0,64
10,97 +-0,45
10,92 +-1,59
4,4 +-1,35
4,96 +-0,87
4,75 +-1,02
BMI [kg/m2]
27,5 +-2,47
28,4 +-2,45
28,22 +-1,77
31,83 +-2,25
28,52 +-1,32
29,76 +-2,32
DM age [luni]
22,42 +-36,25
11,38 +-23,62
16,9 +-32,22
38,23 +-62,16
50,27 +-80,14
44,25 +-60,76
14
1. Type 2 diabetes is a complex disease associated with an
increased risk of ischemic heart disease and premature death. Among
patients with acute coronary syndrome and stroke have predominantly
In this study we evaluated the efficacy and safety of atorvastatin
in lowering cardiovascular risk, given at a dose of 10 mg/day and 20
mg/day on lipid metabolism, glycemic and inflammatory biomarkers in
patients with type 2 diabetes without manifest cardiovascular disease
and in patients with acute cardiovascular events, which were given
treatment for a period between 4 and 24 weeks.
In our study we found evidence of benefit for patients whose
treatment with statins resulted in concentrations of hs-CRP of less than
2 mg/l, whether levels of LDL cholesterol were reduced to the target
value of less than 70 mg/l or not. In this respect, our data are
consistent with research witch indicating inflammation as a factor of
plaque instability and experimental data showing that statins, in
addition to lipid lowering effect, also have important anti-inflammatory
effects [42].
In our study, oxidized LDL levels were significantly higher values
in diabetic patients untreated with lipid-lowering compared with diabetic
patients treated with atorvastatin, regardless of cardiovascular status.
Significant changes in this biomarker were recorded depending on the
dose of atorvastatin in type 2 DM patients without manifest
cardiovascular disease (A2) - 10 mg/day: 70.75 ± 3.32 U/l vs. 20
mg/day: 60.24 ± 7.54 U/l.
6. Conclusion
15
men aged 60-80 years.
2. In acute cardiovascular events diabetes is not only an
important cardiovascular risk factor, but has a strong impact on other
risk factors- hypertension, elevated total cholesterol, triglycerides, low
HDL-cholesterol- showing a tendency to associate their the same
patient.
3. Glicate hemoglobin and blood sugar levels, total cholesterol
and LDL cholesterol were not significantly affected by the dose of
atorvastatin administered, but blood glucose was as high as the
effectiveness of statins in reducing lipids was lower.
4. Patients with received low-dose atorvastatin (10 mg/day or 20
mg/day) long term (12-24 weeks) had lower blood glucose levels
(statistically insignificant) than those who received short-term treatment
(4-8 weeks)
5. The group of patients without manifest cardiovascular disease,
diabetes mean age was 42.61 ± 57.86 months and the group of
patients with acute cardiovascular events 29.05 ± 49.49 months, which
proves, surprisingly and contrary data literature, that age of type 2
diabetes does not influence the incidence of acute cardiovascular
events. Myocardial infarction or stroke, in diabetic patients, may occur
regardless of age diabetes, but dependent on the existing metabolic
imbalance.
9. Oxidized LDL and hs-CRP were significantly elevated in
patients with acute myocardial infarction or stroke than those without
manifest cardiovascular disease, irrespective of lipid profile of patients,
suggesting that may be considered independent predictive factors for
cardiovascular risk.
10. Our research findings suggest a higher sensitivity of hsCRP
at atorvastatin therapy compared with oxidized LDL, both in patients
16
without manifest cardiovascular disease, and especially in patients with
acute MI or stroke.
11. Treatment with statins reduce hsCRP levels in a manner that
is largely independent of LDL cholesterol level, but lack of evidence
linking a greater reduction in hsCRP levels by reducing the rate of
cardiovascular events.
15. Statins exercise beneficial pleiotrope effects on vascular wall
cells. Treatment with statins was one of the most significant advances
in prevention and treatment of atherosclerosis. The benefits of statin
therapy in reducing cardiovascular risk extend beyond their effects on
serum lipids.
16. In general, statins are well tolerated drugs, the primary side
effect is hepatotoxicity, which increases in direct proportion to the dose
of statin administered and seems to not be influenced by the duration
of treatment.
17. Atorvastatin, at doses of 10 mg/day and 20 mg/day, did not
cause a deterioration in the biological samples of liver (ALT, AST),
requiring discontinuation of therapy.
18. Because clinical trials with statin therapy was initiated only on
total cholesterol and LDL cholesterol, suggest that evaluation of
biomarkers hsCRP and oxidized LDL is an objective way to assess the
need for administration of statins, and establishing the effectiveness of
statins in preventing acute cardiovascular events.
17
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5.
Curriculum vitae Name: Floriana Elvira Ionică Place and date of birth: 20.11.1967, Craiova Marital status: married, 2 children Studies: 1982-1986 Medical High-School Craiova, 1998-2003 University of Medicine and Pharmacy of Craiova,
Faculty of Pharmacy, 2004-2006 University of Medicine and Pharmacy Carol Davila
Bucharest, specialty residency in Clinical Pharmacy; Scientific title: 2005 and currently PhD in Pharmacology, University of Medicine
and Pharmacy of Craiova. Professional Experience: 2004 -2006 academic research assistant, through competition,
University of Medicine and Pharmacy Craiova, Faculty of Pharmacy, Department Toxicology,
2006 - present Assistant Professor, through competition, University of Medicine and Pharmacy Craiova, Faculty of Pharmacy, Department Toxicology.
Experience in national research projects: 1. „Establish methodology for licensing and marketing of national
medicinal products at European”, during 2004-2006, the contracting authority SC Arena Group SA Bucharest.
2. „Clinical study on the association with metronidazole 250 mg amoxicillin 500 mg in the treatment of duodenal ulcer with HP positive”, during 2005-2007, the contracting authority SC Arena Group SA Bucharest.
3. „Clinical study on prophylactic use of cefuroxime capsules in the treatment of open injuries of the hand and forearm”, during 2005-2007, the contracting authority SC Arena Group SA Bucharest.
4. „Study on sensitivity to Cefuroxime 250 mg capsules of gram-negative bacilli Pseudomonas aeruginosa involved in the etiology of urinary infections”, 2007-2009, the contracting authority SC Arena Group SA Bucharest.
"Assessing the efficacy and safety of statin therapy in preventing cardiovascular risk in patients with type 2 diabetes based on serum levels of inflammatory markers”, 2007-2009.
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Specialization and Qualifications: 2006- Clinical pharmacy specialty.
Member of scientific and professional societies: Society of Pharmaceutical Sciences of Romania, Romanian Society of History of Pharmacy, College of Pharmacists in Romania. Foreign languages: English.
List of works published
Books: CNCSIS recognized national publishers: 1. Eliza Gofiţă, Floriana Ionică „Mineral, volatile and gaseous
toxic- analysis and toxicological evaluation”, 2005, Ed. Medical University, Craiova.
2. Vere Cristin, Forţofoiu Cătălin, Floriana Ionică, 2006, „Semiology and medical terminology”, Ed. Medical University, Craiova.
3. Eliza Gofiţă, Floriana Ionică -2007 „Drug Toxicology”, Ed. Medical University, Craiova.
4. Under the management Mariana Aciu, Florica Popescu, „Practical guide for students of V Pharmacy”, 2008, Ed. Medical University, Craiova.
Full papers published in journals listed CNCSIS: Type B: 1. Eliza Gofiţă, Floriana Elvira Ionică M. Bojiţă: "Routes of drug
recognition by human T lymphocytes αβ and hypersensitivity reactions”, Clujul Medical, Vol 80, Nr. 3, p. 584-590, 2007.
Type C: 1. Eliza Gofiţă, Floriana Elvira Ionică, L. Bejenaru, Cornelia
Bejenaru, D.G. Mogosanu: „Acute poisoning with tricyclic antidepressants (ADT)”, Craiova Medicală, Vol 6, Nr. 1, p. 28-33, 2004.
2. E. Gofiţă, L. Bejenaru C. Bejenaru, Floriana Elvira Ionică, G.D. Mogosanu: „New aspects of toxicology paracetamol” Craiova Medicală, Vol 6, Nr. 2, p. 180-190, 2004.
3. Eliza Gofiţă, Floriana Elvira Ionică: "Interaction of the β-adrenolitics with glimepiride in combination therapy", Craiova Medicală, Vol 9, Nr. 4, p. 394-397, 2007.
Floriana Elvira Ionică, Florica Popescu, Catalina Pisoschi, Eliza Gofiţă: "Clinical consequence of the physicochemical properties of LDL particles in type II diabetes”, Craiova Medicală, Vol 35, Nr. 1, p. 75-80, 2009.
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5. Floriana Elvira Ionică, Pisoschi Catalina, Maria Mota, Florica Popescu, Eliza Gofiţă "Statins therapy, C-reactive protein (CRP) levels and type 2 diabetes", Craiova Medicală, Vol 35, Nr. 2, p. 87-91, 2009.
6. Floriana Elvira Ionică, Maria Moţa, Diana Protasiewicz, Eliza Gofiţă: „Pleiotropic effects of statins and cardiovascular benefits", Romanian Journal of Diabetes, paper accepted for publication in november 2009.
Abstracts of some papers (communications/posters)
published in volumes of international scientific meetings (with ISBN):
1. Florica Popescu, C. Vere, Floriana Ionică, Eliza Gofiţă:
„Effect of antiviral therapy on the extrahepatic manifestation in chronic hepatitis C”. Pharmaceutical sciences world congres, Amsterdam 22-25 April 2007.
2. Florica Popescu, Eliza Gofiţă, Floriana Ionică, C. Vere: „Hepatic side effect of simvastatin therapy in pacients addmited in a medical clinic.” Pharmaceutical sciences world congres, Amsterdam 22-25 April 2007.
Abstracts of some papers (communications/posters)
published in volumes of scientific national (with ISBN): 1. Floriana Ionică, Gofiţă Eliza "Acute poisoning with hypnotic
barbiturates: incidence, clinical-toxicological evaluation and prognosis”, UMF Craiova Day edition XXXIV-A, p. 268-269, 4-5 June, 2004.
2. Floriana Ionică, Florica Popescu, C. Vere: "A comparative study H2 antihistamines - proton pump inhibitors in the treatment of gastric and duodenal ulcer”, UMF Craiova Day edition has XXXIV, p. 264, 4-5 iunie, 2004 .
3. Floriana Ionică, Eliza Gofiţă: "Ecstasy, a potentially fatal choice for adolescents and youth”, UMF Craiova Day edition has XXXV, 3-4 June, p. 328, 2005.
4. Floriana Ionică, Florica Popescu, Eliza Gofiţă: "The action of HMG-CoA reductase inhibitors on increased levels of C-reactive protein” - Scientific Symposium" 10 years of pharmaceutical education university Craiova "UMF Craiova, p. 28-29, 18-20 May, 2006.
Floriana Ionică, Florica Popescu, C. Vere, Eliza Gofiţă: "The incidence of hepatic adverse effects of therapy with simvastatin in patients hospitalized in a medical clinic” - VII National Congress of Pharmacology, Therapeutics and Clinical Toxicology Timisoara, 2006.
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6. Vere C., Ionică Floriana, Marinela Beznă, Genunche Amelia, Rădoi Olimpia, Raluca Sandu, Dragomir Liliana: "Antiviral therapy in patients with chronic viral hepatitis C admitted to a medical clinic”. Days UMF Craiova edition has XXXVI, 9-10 June, p. 354, 2006.
7. Vere Cristin, Floriana Ionică, Gabriela Iliescu, Olimpia Radoi, Liliana Dragomir: "Incidence of side effects of antiviral therapy of chronic hepatitis C". Journal of Gastrointestinal and Liver Diseases. XXVII-th National Symposyum of Gastroenterology Hepatology and Digestive Endoscopy-Poiana Brasov, June 14-17, 2006.
8. Vere C., Floriana Ionică, Amelia Genunche, Marinela Beznă, Daniela Neagoe, Luminita Stingheru: "The incidence of cholestasis in patients hospitalized in a medical clinic”. Days UMF Craiova-edition has XXXVII, 8-9 June, 2007.
9. Vere Cristin, Floriana Ionică, Amelia Genunche, Marinela Beznă, Daniela Neagoe: "Influence of antiviral therapy on cholestasis syndrome in chronic viral hepatitis C". Journal of Gastrointestinal and Liver Diseases. The 28th National Symposium of Gastroenterology, Hepatology, Digestive Endoscopy, Sibiu, 14-16 June 2007.
10. Floriana Elvira Ionică, Eliza Gofiţă, Ioana Raluca Gofiţă Cojocaru: "C-reactive protein (CRP) and cardiovascular risk in type II diabetes”. Days UMF Craiova-edition XXXIX-of, 5-6 June 2009.