ISSN 0326-646X





Sumario Vol. 42 - Nº 1 Enero - Marzo 2013

Impact of lower cholesterolemia in the flow reserve of the coronary microcirculation.

Graciela R. Reyes, Ricardo E. Ronderos, Diomedes B. Corneli, Jorgelina Testore, Nora G. Fabris, Marcelo L. Portis.

Instituto de Cardiología La Plata.
Calle 6, Nº212, La Plata (1900), Argentina.
TE: 0221-4271000 - Fax 0221-4271800.
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Recibido 20-MAYO-12 – ACEPTADO después de revisión 17-NOVIEMBRE-2012.

The authors declare not having a conflict of interest.

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The purposeof this studywas to analyzethe effects of treatment withatorvastatin onflow reservein thecoronarymicrocirculation, in patients with hypercholesterolemia without cardiovascular disease.
Material and Methods:we selected 23 patients <55years withhypercholesterolemia, without other cardiovascular risk factors except smoking<10cigarettes /day. Eight patients were excluded because blood cholesterol levels showed significant improvement after 1 month of diet and exercise All the other 15 patients were treated with atorvastatin 20 mg/day and diet during 90 days. Myocardial perfusion imaging studies were performed using Philips Sonos 7500 with real time myocardial perfusion software. Optison was injected by continuous infusion through a peripheral vein. The Coronary microcirculation Reserve (CR) was estimated in the different coronary territories, before and after  dipyridamole injection (0.84 mg/kg), at the beginning  and after treatment, using arithmetical curves of bright intensity/ time, considering the percentage of b increase as the coronary flow reserve.
Results: Pre-Treatment: Total Chol 305.64mg/% ± 53.80mg/%, HDLc 44.09mg/% ± 9.36mg/% and LDLc 233.45mg/% ± 59.47mg/%. Glucose 104.18mg/% ± 10.68mg%, triglycerides 194.82mg/% ± 122.49mg%. Post-Treatment: Total Chol 235.09mg/% ± 34.99mg/% (p<0.0001), HDLc 48.64mg/% ± 7.71mg/% (ns) LDLc 93.18mg/% ± 37.89mg/% (p<0.0001). Glucose 93.81mg/% ± 9.81mg/% CR: Pre-treatment: basal, ß 0.78 ±0.64 in LAD, 0.38 ± 0.23 in Cxand 0.65± 0.50 in RCA. Post-dipyridamole 2.46±1.78 in LAD, 1.14 ± 0.57 in Cx and 1.42 ± 1.1 in RCA. Coronary reservewas 214% in LAD, 202% in Cxand 117% in RCA; in the 3 territories 177.66% ± 52.88%. Post Treatment: Basal, ß 0.98 ± 0.65in LAD, 0.57 ±0.20 in Cxand 0.9±0.45 in RCA. Postdipyridamole: 2.5 ± 1.56 in LAD, 1.5 ± 0.78 in Cxand 1.4 ± 08 in RCA. Coronary reserve was 245% in LAD, 86% in Cxand 126% in RCA. In the 3 territories 152% ± 48%. (NS compared with pretreatment).
Conclusions: Coronary reserve is abnormal in asymptomatic patients with hypercholesterolemia and does not improve after 90 days of treatment with atorvastatin.

Key words: Coronary flow reserve. Dipyridamole. Atorvastatin. Coronary riskfactors. Hypercholesterolemia. Myocardial contrast echocardiography.
Rev Fed Arg Cardiol. 2013; 42(1): 35-42




Hypercholesterolemia has been related to the process of developing atherosclerotic disease, with an important body of evidence in that regard [1-3].

The international guidelines such as ATP III have defined the LDL cholesterol levels for primary prevention in <160 mg/% and for secondary prevention in <130 mg/% or <100 mg/% in the individuals in high risk [3-8].

Epidemiology studies support these recommendations, and show the beneficial effect of the treatment with different drugs of the group of statins, in the reduction of cardiovascular events, all-cause death and death by cardiovascular cause. In all of these cases, there is a relation between the level of LDL cholesterol decrease by effect of drugs associated to diet and physical activity, and the level of reduction of events [3,9-12]. However, the mechanisms that explain these benefits have not been clearly and fully exposed [13-18].

Carotid ultrasonography and magnetic resonance studies suggest regression of atherosclerotic plaques as a result of management with statins, in relation to the level of decrease of LDL cholesterol figures and a lower impact in relation to the HDL cholesterol increase [19,20].

Coronary flow reserve (CFR) is the maximal capacity of vasodilation of the coronary bed before an increase in the demand of myocardial oxygen.

Microvascular resistance to the coronary flow depends mainly on the small arterioles (50-60% of total resistance) and to a lower extent of coronary capillaries (20% of total resistance). Epicardial vessels play a minor role in relation to resistance to flow; they behave as conductance vessels and provide approximately 5% of the total resistance to coronary flow.

The normal value of CFR can be estimated in the flow increase >2.5-3 times before a vasodilator stimulus or in response to hyperemia (according to the author) and this may vary in relation to different variables, as the age group evaluated and the degree of physical training (it decreases in >50 years and increases in young sportsmen). CFR may decrease by increase in basal flow velocity or by incapacity to increase in an appropriate way due to functional or structural alteration of microvasculature [21-24].

Echocardiography, with the use of contrast agents, allows to quantify the volume of blood contained in the myocardium and the flow velocity in coronary microcirculation, by a quantitative analysis performed using mathematical models of curves that relate the intensity of the shine obtained in the myocardium before and during ultrasound contrast injection (expressed in decibels) and the time in which this occurs (1-exponential). With this application, the percentage of change of increase in the shine according to time can be estimated both for maximal shine (A) that expresses the volume of blood contained in the area being studied, as for the maximal velocity of increase of shine, estimated as the maximal velocity of coronary flow (β), considering as normal an increase of 250-300% in this velocity after the injection of a vasodilator such as adenosine or dipyridamole [25,26].

Echocardiography studies of myocardial contrast in real time (MCE) allow a quantitative and semi-quantitative evaluation of the blood flow in coronary microcirculation, both in rest as during the effect of exercise, dobutamine and the use vasodilators such as adenosine and dipyridamole. The latter have as main effect reducing the resistance of microvasculature, increasing the velocity of coronary flow, without increasing capillary recruitment, just as exercise or other drugs increasing the consumption of myocardial O2 [26-29]. Evidence shows that the reduction in the level of plasmatic cholesterol improves the regulating function of the microvascular endothelium and therefore, the capacity to regulate flow by the effect on the coronary microcirculation vessels.

According to this evidence, it is possible to pose the hypothesis that the decrease in plasma levels of LDL cholesterol, by effect of diet, exercise and the administration of atorvastatin, will produce an improvement in the flow reserve in coronary microcirculation in patients with hypercholesterolemia.

The Objective of this work is to analyze the effect of the treatment with atorvastatin on the flow reserve in the coronary microcirculation in young adults with hypercholesterolemia as the single cardiovascular risk factor.


Prospectively, 23 (twenty three) patients were selected: <55 years old, of both genders (5 males), the inclusion criteria for whom were: not presenting history of cardiovascular diseases, diabetes mellitus or hypertension, besides not presenting overweight or sedentarism, smoking (defined as consuming >10 cigarettes per day) and having total cholesterol levels >240 mg/%, LDL cholesterol >160 mg/% without treatment with no lipid-lowering drug. In the case of patients that smoked but <10 cigarettes per day, it was demanded from them to suspend the consumption of tobacco for 48 h prior to the study.

Patients who had any alteration in the basal ECG, bronchial asthma, chronic bronchitis, COPD, or any history of intolerance or allergy to dipyridamole, aminophylline and/or statins were excluded, as well as all those who required any other treatment with drugs for any concomitant pathology and smokers with a consumption greater than 10 cigarettes per day.

The patients selected were asked to sign an informed consent, approved by the Committee on Ethics of the Instituto de Cardiología La Plata, for them to undergo a 12-lead ergometer test and/or stress echocardiogram with exercise. Once the stress test was made, in those individuals in whom the result was normal, blood samples with 12 hours of fasting state were taken, to determine total cholesterol, LDL-C and HDL-C (lipase/oxidase/peroxidase method), glycemia and plasma level of triglycerides in lab credited by the Fundación Bioquímica Argentina according to the CDC USA guidelines.

Immediately after taking the sample, a stress echo was made with dipyridamole (0.84 mg/kg up to a maximal total dose of 60 mg) with technology of contrast to evaluate the myocardial perfusion in real time using a Philips sonos 7500 echograph.

The studies were made with technology of harmonic Doppler of amplitude with inversion of pulses or modulation of amplitude, using as contrast agent OPTISON® diluted in 20 cc of saline solution, administered by infusion pump 2-4 ml/mm with a low mechanical index (MI) for the observation of myocardial perfusion in real time and a flash of high energy (transient increase of MI), with the aim of obtaining the destruction of microbubbles of the contrast agent. Clips of the digital video were obtained in rest and after IV injection of dipyridamole and up to 10 beats after the flash of energy, of the apical views of 4, 2 and 3 chambers. The analysis and quantification were made off-line with QLAB software (Philips) version 4.0, commercially available.

For the quantification of the flow in the 3 coronary territories, the volume of the sample was positioned in the interventricular septum to evaluate the flow in the territory of the Anterior Descending artery (ADA), in the lateral side of the LV for the territory of the circumflex artery (Cx) and in the inferior side for the territory of the Right Coronary artery (RCA). In the video clip, the frames or postflash frames were selected manually for the start of the analysis, and after 3 frames at the end of each systole for 7 to 10 postflash beats (Figure 1).

Figura 1 A
Figura 1 B
Figura 1 C
Figura 1 D
Figura 1 E

Figure 1 A) Outline of the timeline of the loop of the digital video (upper part), with the FLASH frames highlighted in red. B) Myocardial perfusion image corresponding to the loop described in the timeline of A. C) Areas of interest (ROI) located in the territory of the ADA (M0) and Cx (M1), in 4-chamber apical view. D) Clipping of the timeline of the digital loop with start of the 1st post-flash frame and after 3 frames at the end of each systole for 8 cardiac cycles. E) Below,the arithmetic quantification and 1-exponential of the increase in shine in the time function in the ROI of the ADA. At the onset of the 1-exponential curve, the maximal velocity of increase in shine according to β time was obtained.


For the arithmetic graphs on the intensity of the shine in each frame according to time, a Cartesian coordinate system was used, adjusting the curve according to the 1-exponential mathematical model. From the latter, the data on maximal velocity of flow (β) was obtained in rest and after injection of dipyridamole in the 3 coronary territories (Figure 1).

The percentage of change of β in each territory after dipyridamole in relation to β before the injection of the vasodilator, was considered as the flow reserve in coronary microcirculation, taking as normal an increase ≥200%.
Biochemical and echocardiographic studies were repeated 3 months after the first study considered basal, after the treatment with diet, physical activity and 20 mg/day of atorvastatin orally. Atorvastatin 20 mg was provided free of charge in its commercial package of 30 pills monthly, during the whole treatment, using the same drug in the same package by the same supplier for all the patients. The results of these tests repeated with equal methodology were considered post-management results.


The results of each patient were compared between those considered basal and post-treatment, using a control case model for each patient.

Median and Wilcoxon test with paired samples were used, considering as significant a value of p<0.05.


From the 23 patients that were included in the study protocol, 8 patients with mild dyslipidemia were excluded, since after 1 month of treatment with diet and physical activity they had total cholesterol values in the reference lab of the study of <240 mg/%. A patient was excluded due to the impossibility to obtain a proper peripheral venous via for the contrast injection, 1 patient because he had suffered upper gastrointestinal bleeding 1 week after having started the treatment with atorvastatin and 1 patient due to technical alterations in the digital acquisition of post-treatment study.
The 12 remaining patients, 5 men and 7 women, with an average age of 41.82 years old ± 10.2 years old (34-53 years old) completed the protocol without presenting complications or adverse events.


The values of total cholesterol in the admittance to the protocol was in average 305.64 mg/% ± 53.80 mg/%; with HDL-C 44.09 mg/% ± 9.36 mg/% and LDL-C 233.45 mg/% ± 59.47 mg/%. The levels of glycemia were 104.18 mg/% ± 10.68 mg/% and triglycerides 194.82 mg/% ± 122.49 mg/%.

After 3 months of treatment with atorvastatin, the levels of total cholesterol were 235.09 mg/% ± 34.99 mg/% (p<0.0001), HDL-C 48.64 mg/% ± 7.71 mg/% (NS) and LDL-C 93.18 mg/% ± 37.89 mg/% (p<0.0001). Post-treatment glycemia was 93.81 mg/% ± 9.81 mg/% (NS) in comparison to the pre-treatment levels (Figure 2).

Figure 2. The graph represents the serum values of total cholesterol, HDL, LDL, Triglycerides and glucose, before and after the treatment with atorvastatin 20 mg/day for 3 months in the study group of 12 patients.


The values of β in rest were in average 0.78 ± 0.64 in the ADA territory, 0.38 ± 0.23 in the Cx and 0.65 ± 0.50 in the RCA. After injection of dipyridamole, 2.46 ± 1.78 in the ADA, 1.14 ± 0.57 in the Cx and 1.42 ± 1.1 in the RCA. The percentage of increase of β after the vasodilator (CFR) was 214% in the ADA, 202% in the Cx and 117% in the RCA. The average of the RC in the 3 territories was 177.66% ± 52.88%.

The values of β in rest were in average of 0.98 ± 0.65 in the territory of the ADA, 0.57 ± 0.20 in the Cx and 0.9 ± 0.45 in the RCA. After the injection of dipyridamole 2.5 ± 1.56in the ADA, 1.5 ± 0.78 in the Cx, and 1.4 ± 0.8 in the RCA. The percentage of increase of β after the vasodilator (CFR) was 245% in the ADA, 86% in the Cx and 126% in the RCA. The average of CR in the 3 territories was 152% ± 48% (Figure 3).

Figure 3. The graph represents the reserve of circulation in coronary microcirculation, expressed in the percentage of increase of post-dipyridamole β, in the average of the 3 coronary territories and each coronary territory in the total group of patients, before and after the treatment with Atorvastatin for three months.

Analysis of the results of the measurement or coronary reserve pre- vs. post-treatment
The percentage of increase of post-dipyridamole (CFR) β in the territory of the ADA pre-treatment (214%) vs. post-treatment (245%) was 31% (NS). In the territory of the Cx there was no increase of the CFR post-treatment, but a decrease – 116% (p<0.05), while in the territory of the RCA, there was an increase of just 7% (NS).

If the averages of CFR are compared in the 3 coronary territories, the pre-treatment (117.66% ± 52.88%) is not significantly different from the post-treatment value (185% ± 30.8%).


The patients with increased blood cholesterol in isolated form, who do not correspond to familial hypercholesterolemia, are not common in clinical practice, since in the average adult age, this cardiovascular risk factor is usually associated to others such as obesity, hypertriglyceridemia, and hypertension. In fact, this was the first problem in the prospective selection of the population for this study, since the repetition of the biochemical studies of the pre-selected patients for their non-controlled lab data, in the reference lab, yielded very different results, which forced to dismiss up to 80% of the initially selected patients.

For this reason, the thoroughness of the quality control of the usual biochemical analysis in our area would not be uniform.

In that regard, the absence of triglyceride increase, associated to cholesterol increase, was not a fact easy to avoid. In the population of the study, the average of triglyceridemia was greater than the normal parameters, since 2 patients were markedly away from normal values, significantly influencing the arithmetic average of the sample being studied. It was decided to keep these patients in the sample, as long as results were obtained during the treatment of the protocol, that would reflect a significant decrease of LDL-C, the goal of the study. The individual analysis of these 2 patients did not yield in terms of values of coronary reserve modification, differences in regard to the patients with normal levels of triglyceridemia.

Smoking is a known factor of cardiovascular risk, and its effect on the endothelial function has been studied in the clinical field, both with the use of the brachial hyperemia test, as with myocardial flow studies using PET with ammonia n-13[30-32]. Although a decrease in the flow reserve has been shown in the microcirculation of smokers, the greatest effects occur immediately after smoking. For this reason, the few patients with mild smoking habit, were included under the commitment of not smoking during the 48 h prior to both echocardiographic studies.

The population finally included in the study, would be representative of dyslipidemic patients in low cardiovascular risk and homogeneous as to dispersion of data. Table 1.

In these populations, it is accepted that the goal of the lipid-lowering therapy, is to decrease LDL-C levels below 160 mg/%. This goal was met in this protocol in all patients, with an average of LDL-C below these figures. These results should not be surprising, since the background published on the treatment with atorvastatin in standard doses of 20 mg/day, show reliably that 20 mg/day of this drug is capable of producing a decrease in LDL-C [33,34] Table 1.

Values in a fasting state of total cholesterol, HDL-C, LDL-C and
Glycemia at the beginning of the study, and after the treatment
for 3 months with atorvastatin 20mg/day.













































































































* Valores expresados todos en mg %; Pte: Paciente; COLt: Colesterol total;
: HDL colesterol; LDLc: LDL colesterol; GL: Glucemia; y luego de 3 meses de tratamiento
: Colesterol total; HDLc2: HDL colesterol; LDLc2: LDL colesterol; GL2: Glucemia.

It is possible to conclude then, that the results obtained in the population in study, reaches the prevention levels proposed by ATP III levels.

The time of treatment of just 3 months could entail a controversial point in regard to the desired effects in coronary microcirculation. However, the current knowledge on the topic, although it does not define clearly the time required for the treatment to obtain circulatory benefits, may suggest that the benefit is obtained in a linear proportion with the decrease of plasma levels of cholestero l[35]. Although there are no data existing in literature about a standard of increase in flow velocity in coronary microcirculation, and those that can be consulted depend on the use of different methods of analysis (PET, Doppler, etc.) it seems clear the expected increase in coronary flow velocity in microcirculation or in the epicardial coronary arteries, should be greater than 200% (twice the flow velocity in rest).

The studies with PET show an increase in flow velocities of up to 400%, and in our own experience, these velocities are obtained in a viable myocardium after primary revascularization in acute myocardial infarction, but recent works about the quantification of the flow reserve in microcirculation seem to define a 200% increase after the administration of dipyridamole, as the minimum necessary to consider the presence of a proper regulation of intra-myocardial coronary flow [36,37].

In the population in study, the measured velocities present an important dispersion, both in rest and after the vasodilator action. This dispersion can be explained in part, by reasons inherent to the echocardiographic technique proper. The territories located in the lateral region of the field insonified by the transducer, for example the lateral side of the left ventricle in the 4-chamber view, or the inferior side in the 2-chamber view, if this is not located in the center of the ultrasound beam, they show shine intensity of lower magnitude  than those territories located in the center of the ultrasound beam emitted by the transducer. These differences are due to the distribution phenomenon of ultrasound energy, which is significantly greater in the central region than in the lateral ones of the insonified area. For this reason, it is important not to consider the absolute values of β, but its percentage variation in the same patient and in the same territory before and after the action of dipyridamole [38,39].

The increase of myocardial flow velocity in microcirculation (β) in response to the dipyridamole injection, is evenly decreased in the dyslipidemic patients included in this study. This decrease is present in all the coronary territories, and is close to the basis of 200% expected, in the study made when starting the protocol.

After the treatment with atorvastatin, the values of β after the action of the dipyridamole increase mildly, in a non significant statistical manner and always close to the basis of 200%, in spite of achieving plasma values of LDL-C in the order proposed by the ATP III guidelines.

The absence of improvement in the flow reserve in coronary microcirculation, could be explained in different ways:
-The dose of atorvastatin used was not enough to achieve the normalization of the regulation mechanisms of microcirculation, and/or the time of treatment was below the proper one.
-The mechanisms of impairment of self-regulation are not dependent on LDL-C levels.
-The beneficial effect of the use of statins to reduce the cardiovascular events in general and coronary events in particular, are independent from their action on the self-regulation mechanisms of the coronary flow.

The atorvastatin dose used, although not the highest that could be prescribed and that have shown benefits in acute coronary syndromes or after myocardial revascularization by angioplasty, are those recommended in primary prevention, which correspond to the population being studied, and were enough to reduce the levels of total cholesterol and LDL cholesterol in the amounts recommended for populations in low risk and without history of cardiovascular events.

Although the time of duration of the treatment in this protocol was short, there is no conclusive evidence suggesting that more prolonged therapies may modify the effects of the drug in this regard. Higher doses in longer terms of treatment should be attempted.

There is evidence that the beneficial effect of statins, linearly related to the levels of decrease of cholesterolemia, manifest in the reduction of cardiovascular morbi-mortality. However, direct effects on the atheroma plaques, “pleiotropic” effects and/or anti-inflammatory agents would play an independent role from their lipid-lowering effect in the reduction of risks of cardiovascular events. These results seem to generate evidence in this regard, however the population studied is small as to conclude that the effects of statins do not produce significant changes in the altered mechanisms of self-regulation of the coronary flow. These data suggest the need to increase the number of patients to be probably treated with lipid-lowering agents in greater doses and for more extended times.


Atorvastatin in doses of 20 mg/day is effective to reduce the figures of total cholesterol in blood and LDL-C in patients with hypercholesterolemia and low cardiovascular risk.

These patients already present a decrease in the coronary microcirculation reserve, which persists after the normalization of the figures of serum cholesterol mediated by the usual treatment of diet and atorvastatin.



  1. Klag MJ, Ford DE, Mead LA, et al. Serum cholesterol in young men and subsequent cardiovascular disease. N Eng J Med 1993; 328: 313-318.
  2. Jacobs D, Blackburn H, Higgings M, et al. Report of the conference on Low Blood Colesterol: Mortality Association. Circulation 1992; 86: 1046-1060.
  3. Athyros VG, Mikhai Lidis DP, Papageorgiou AA, et al. Effect of atorvastatin on High density lipoprotein cholesterol and its relationship whith coronary events: a subgroup analysis of the GREek Atorvastatin and coronary- heart- disease Evaluation (GREACE) Study. Curr Med Res Opin 2004; 20 (5): 627-637.
  4. 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 Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486-2497.
  5. Kashyap ML, Tayintharan S, Kamanna VS. Optimal therapy of low levels of high density lipoprotein-cholesterol. Am J Cardiovasc Drugs 2003; 3 (1): 53-65.
  6. Pasternak RC. Report of the Adult Treatment Panel III: The 2001 National Cholesterol Education Program guidelines on the detection, evaluation and treatment of elevated cholesterol in adults. Cardiol Clin 2003; 21 (3): 393-398.
  7. Morgan JM, Capuzzi DM. Hipercolesterolemia. The NCEP Adult Treatment Panel III Guidelines. Geriatrics 2003; 58 (8): 33-38.
  8. Linton MF, Fazio S. National Cholesterol Education Program (NCEP)- the third Adult Treatment Panel (ATP III).A practical approach to risk assessment to prevent coronary artery disease and its complications. Am J Cardiol 2003; 92 (1A): 19i-26i.
  9. Shepherd J, Hunninghake DB, Barter P, et al. Guidelines for lowering lipids to reduce coronary artery disease risk: a comparison of rosuvastatin with atorvastatin, pravastatin, and simvastatin for achieving lipid-lowering goals. Am J Cardiol 2003; 91 (5A): 11C-17C. Discussion 17C-19C.
  10. Fonarow GC. National Cholesterol Education Program (NCEP) Treating to goal: new strategies for initiating and optimizing lipid-lowering therapy in patients with atherosclerosis. Vasc Med 2002; 7 (3): 187-194.
  11. Jacobson TA, Griffiths GG, Varas C, et al. Impact of evidence-based "clinical judgment" on the number of American adults requiring lipid-lowering therapy based on updated NHANES III data. National Health and Nutrition Examination Survey. Arch Inter Med 2000; 160 (9): 1361-1369.
  12. McKenney JM. Pharmacologic options for aggressive low-density lipoprotein cholesterol lowering: benefits versus risks. Am J Cardiol. 2005; 96 (4A): 60E-66E.
  13. Schatz IJ, Masaki K, Yano K, et al. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet 2001; 358: 351-355.
  14. Strandberg TE, Salomaa VV, Vanhanen HT, et al. Mortality in participants and non participants of a multifactorial prevention study of cardiovascular diseases. A 28 year follow up of the Helsinski Businessmen Study. Br Heart J 1995; 74: 449-454.
  15. Mosca L, Apple LJ, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004; 109: 672-693.
  16. Schaefer EJ, Lamon Fava S, Cohn SD, et al. Effects of age, gender and menopausal status on plasma low density lipoprotein cholesterol and apoprotein B levels in the Framingham Offspring Study. J Lipid Res 1994; 35: 779-792.
  17. Campos H, Mc Namara JR, Wilson PWF, et al. Differences in low density lipoprotein subfractions and apolipoproteins in premenopausal and postmenopausal women. J Clin Endocrinol Metab 1988; 67: 30-35.
  18. Rozansky A, Blumenthal JA, Davidson KW, et al. The epidemiology, Pathophysiology, and Management of Psychosocial Risk factors in cardiac Practice: The Emerging Field of Behavioral Cardiology. J Am Coll Cardiol 2005; 45: 637-649.
  19. Atsushi Y, Yukihiko M, Zahi A, et al. Effect of Lipid- Lowering Theraphy Whith Atorvastatin on Atheroesclerotic Aortic Plaques Dectected by Noninvasive Magnetic Resonance Imaging. J Am Coll Cardiol 2005; 45: 733-742.
  20. Fayad ZA, Nahar T, Fallon JT, et al. In vivo magnetic resonante evaluation of atheroesclerotic plaques in the human thoracicaorta: a comparison whith transesophageal echocardiography. Circulation 2000; 101: 2503-2509.
  21. Fujimoto K, Hozumi T, Watanabe H, et al. Effect of fluvastatin therapy on coronary flow reserve in patients with hypercholesterolemia. Am J Cardiol 2004; 93 (11): 1419-1421.
  22. Stulc T, Kasalova Z, Prazny M, et al. Microvascular reactivity in patients with hypercholesterolemia: effect of lipid lowering treatment. Physiol Res 2003; 52 (4): 439-445.
  23. Voci P, Pizzutto F, Romeo F. Coronary flow: A new assessment for the echo lab? Eur Heart J 2004; 25: 1865-1879.
  24. Lowenstein J, et al. Noninvasive assessment of coronary flow reserve by transthoracic Doppler echocardiography in a general referral population: experience on 957 patients. Eur Heart J 2001; 22 (9) Suppl: 347. Abstr.
  25. Lafitte S, Masugata H, Peters B, et al. Accuracy and reproducibility of coronary flow rate assesment by real-time contrast echocardiography. In vitro and in vivo studies. J Am Soc Echocardiogr 2001; 14: 1010-1019.
  26. Peltier M, Vancraeynest D, Pasquet A, et al. Assesment of the physiologic significance of coronary artery disease with dipyridamole real time myocardial contrast echocardiography. Comparison with technetium-99m sestamibi single photon emission computed tomographyand quantitative coronary angiography. J Am Coll Cardiol 2004; 43: 257-264.
  27. Shimoni S, Frangogiannis NG, Aggeli CJ, et al. Identification of hibernating myocardium with quantitative intravenous myocardial contrast echocardiography and thallium-201 scintigraphy. Circulation 2003; 107: 538-544.
  28. Ronderos RE, Boskis M, Chung N, et al. Correlation between myocardial perfusion abnormalities detected with intermittent imaging using intravenous perfluorocarbon microbubbles and radioisotope imaging during high-dose dipyridamole stress echo. Clin Cardiol 2002; 25 (3): 103-111.
  29. Vogel R, Indermühle A, Reinhardt J, et al. The Quantification of  Absolute Myocardial Perfusion in Humans by Contrast Echocardiography. Algorithm and Validation. J Am Coll Cardiol 2005; 45: 754-762.
  30. Tanriverdi H, Evrengul H, Kuru O, et al. Cigarette smoking induced oxidative stress may impair endothelial function and coronary blood flow in angiographically normal coronary arteries. Circ J 2006; 70 (5): 593-599.
  31. Slart RH, Agool A, van Veldhuisen DJ, et al. Nitrate administration increases blood flow in dysfunctional but viable myocardium, leading to improved assessment of myocardial viability: A PET study. J Nucl Med 2006; 47 (8): 1307-1311.
  32. Sdringola S, Johnson NP, Kirkeeide RL, et al. Impact of unexpected factors on quantitative myocardial perfusion and coronary flow reserve in young, asymptomatic volunteers. JACC Cardiovasc Imag 2011; 4 (4): 402-412.
  33. Karalis DG, Ross AM, Vacari RM, et al. Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary heart disease.Am J Cardiol 2002; 89 (6): 667-671.
  34. Athyros VG, Papageorgiou AA, Mercouris BR, et al. Treatment with atorvastatin to the National Cholesterol Educational Program goal versus 'usual' care in secondary coronary heart disease prevention. The Greek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Curr Med Res Opin 2002; 18 (4): 220-228.
  35. Wei K, Jayaweera AR, FiroozanS, et al. Quantification of  myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a continuous venous infusion. Circulation 1998; 97: 473-483.
  36. Agewall S, Hernberg A. Atorvastatin normalizes endothelial function in healthy smokers. Clin Sci (Lond) 2006; 111 (1): 87-91.
  37. Schäfers KP, Spinks TJ, Camici PD, et al. Absolute quantification of myocardial blood flor with H2 15 O and 3- dimensional PET: an experimental validation. J Nucl Med 2002; 43: 1031-1040.
  38. Tomas JP, Moya JL, Campuzano R, et al. Noninvasive assessment of the effect of atorvastatin on coronary microvasculature and endothelial function in patients with dyslipidemia . Rev Esp Cardiol 2004; 57 (10): 909-915.
  39. Rosas EA, González AM, Castillo LG, et al. Endothelial function assessment by positron emission tomography in patients with hypercholesterolemia Arch Cardiol Mex 2008; 78 (2):139-147.


Publication: March 2013

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