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Vitamin D serum levels are associated with cardiovascular outcome in coronary artery disease
Letters to the Editor
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Vitamin D serum levels are associated with cardiovascular outcome in coronary artery disease Gerasimos Siasos 1, Dimitris Tousoulis ⁎,1, Evangelos Oikonomou, Konstantinos Maniatis, Stamatios Kioufis, Eleni Kokkou, Antigoni Miliou, Marina Zaromitidou, Eva Kassi, Christodoulos Stefanadis 1st Cardiology Department, University of Athens Medical School, “Hippokration” Hospital, Athens, Greece
a r t i c l e
i n f o
Article history: Received 15 May 2013 Accepted 30 June 2013 Available online 26 July 2013 Keywords: Atherosclerosis Coronary artery disease Vitamin D
Coronary artery disease (CAD) is a leading cause of death in western world. Several cardiovascular risk factors such as age, gender, diabetes mellitus, hyperlipidemia, have been recognized and are associated with atherosclerosis progression and adverse prognosis. Recently, the impact of calcium metabolism in the progression of CAD has emerged [1]. Vitamin D has a pivotal role in regulating calcium homeostasis and vitamin D deficiency is now recognized as a situation highly prevalent worldwide. Moreover, low levels of vitamin D are associated with the presence of classic cardiovascular risk factors such as age, obesity,
diabetes mellitus, metabolic syndrome and chronic kidney disease [2,3]. Furthermore, vitamin D deficiency is associated with the presence of subclinical cardiovascular disease, including carotid intima-media thickness, coronary artery calcification and endothelial dysfunction and with overall mortality and cardiovascular risk [4,5]. In the present study we evaluated the diagnostic and prognostic significance of vitamin D status in subjects with established CAD. We consecutively enrolled 252 subjects with CAD. All subjects were treated according to revascularization guidelines with percutaneous coronary intervention and they were followed-up from 3 to 36 months with a median time of 15 months. CAD was defined by coronary angiography as narrowing of more than 50% of at least one major coronary artery. Coronary angiographies were interpreted by at least two experienced cardiologists. On the basis of these coronary angiographies, the number of affected coronary arteries was determined. The severity of CAD was further evaluated by Gensini score and we consider as patients with severe CAD those with a Gensini score more than 80. The baseline characteristics of CAD patients are presented in Table 1. All measurements, in this study were made by the same observer who
Table 1 Characteristics of the study population according to vitamin D status.
Age (years) Male/Female (%) Body mass index (kg/m2) Serum creatinine (mg/dl) Creatinine clearance (ml/min) Hypertension (%) Systolic arterial pressure (mmHg) Diastolic arterial pressure (mmHg) Diabetes mellitus (%) Serum glucose (mg/dl) Dyslipidemia (%) Total cholesterol (mg/dl) Current smokers (%) B blockers (%) ACE inhibitor (%) Angiotensin-receptor blocker (%) Statin (%) Anticoagulants (%) Calcium channel blockers (%) Anti-diabetic medications (%) Vitamin D levels (ng/ml) Gensini score CAD One vessel disease (%) Two vessels disease (%) Three vessels disease (%)
Total study population
Subjects with vitamin D deficiency (88%)
Subjects with vitamin D sufficiency (12%)
P value
62 ± 11 91 28.30 ± 3.70 0.98 ± 0.22 82 ± 18 69 126.4 ± 16.8 78 ± 11 25 113 ± 46 73 159 ± 41 21 73 35 32 86 6 16 22 17.45 (12.51, 24.65) 37 (21, 56)
62 ± 11 88/96 28.37 ± 3.78 0.98 ± 0.23 80 ± 18 67 127 ± 17 78 ± 11 26 114 ± 46 74 159 ± 38 21 75 34 33 87 6 17 22 16.40 (12.08, 21.62) 37(20, 56)
59 ± 9 12/4 28.12 ± 3.26 0.92 ± 0.14 86 ± 15 81 124 ± 19 79 ± 8 21 108 ± 45 69 154 ± 59 21 69 48 24 79 7 10 24 34.80 (31.10, 37,10) 32(24, 62)
0.24 0.25 0.74 0.15 0.10 0.10 0.40 0.59 0.54 0.53 0.59 0.48 0.96 0.49 0.12 0.32 0.27 0.75 0.36 0.78 b 0.001 0.92 0.56
42 34 24
41 35 24
50 25 25
Normally distributed variables are presented as mean ± standard deviation. Skewed variables are presented as median with first and third quartile. Categorical variables are presented as valid percentages. Chi square test was used for categorical variables, t-test for continuous variables normally distributed and Mann-Whitney U test for not normally distributed continuous variables. P values refer to the difference between Subjects with vitamin D deficiency and sufficiency.
⁎ Corresponding author at: Vas. Sophias 114 str, 115 28, Athens, Greece. Tel.: +30 213 2088099; fax: +30 213 2088676. E-mail address: [email protected] (D. Tousoulis). 1 The first two authors (G.S., D.T.) equally contributed in this study.
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Letters to the Editor
Fig. 1. Caption: The association of Vitamin D levels with CAD extent and outcome.Panel A: Box-plots of vitamin D levels for subjects with one, two or three vessels coronary artery disease.Panel B: Kaplan–Meier survival curves for the rate of occurrence of the secondary end point in subjects with vitamin D deficiency and sufficiency.
was unaware of the disease status and treatment condition of the participants. Subjects with low ejection fraction (EF b 50%, as estimated by echocardiography), valvulopathies, acute coronary syndromes or myocardial infarction in the last 6 months, chronic kidney disease with creatinine clearance less than 60 ml/min, comorbidities such as malignancies, or with immunological diseases, hyperparathyroidism or hypercalcemia and subjects receiving systemic glucocorticoids, immunosuppressants, or vitamin D or calcium supplementation were excluded from the study. A fasting venous blood sample was obtained in the morning before coronary angiography. Venous blood samples were centrifuged at 3000 rpm and serum/plasma was collected and stored at −80 °C until assayed. Measures for 25(OH)D were performed in samples that had not been previously thawed, using the sensitive method of Liquid Chromatography Mass Spectrometry/Mass Spectrometry (LC-MS/MS) technology (API 5000 System, Applied Biosystems). The lower limit of quantification was 0.3 ng/ml for 25(OH)D. Subjects with vitamin D levels above 30 ng/ml were characterized as having sufficiency and subjects with vitamin D levels below 30 ng/ml were characterized as having deficiency [6]. Lipids and glucose levels were measured by using commercially enzymatic method. Subjects with CAD were evaluated prospectively up to 36 months. The primary end point was the cardiovascular death and the secondary end point was the composite of death from cardiovas-
cular causes, nonfatal myocardial infarction, nonfatal stroke or hospitalization for cardiovascular causes including stroke, severe recurrent cardiac ischemia, recurrent cardiac ischemia, transient ischemic attack, or other arterial thrombotic event. All statistical calculations were performed using SPSS software (version 18.0; SPSS, Chicago, IL). There was no difference in the baseline characteristics between subjects with vitamin D deficiency and sufficiency as it is shown in Table 1. Spearman's rho coefficient revealed no correlation of Gensini score with vitamin D levels (rho = 0.06, p = 0.36). Accordingly, Kruskal–Wallis test revealed no association of vitamin D levels with the severity of CAD. Therefore, for one, two and three vessels disease the median values of vitamin D with first and third quartile were (17.75 (11.37–23.53) vs. 18.40 (13.65–23.53) vs. 16.90 (12.97– 26.50) ng/ml, p = 0.96) respectively (Fig. 1 panel a). To test the diagnostic accuracy of increased vitamin D levels to detect the presence of severe CAD we perform ROC curve analysis. Vitamin D values had no significant diagnostic ability to diagnose severe CAD as it can be estimated by a Gensini score more than 80 (AUC =0.53, p = 0.52) or by the presence of two or three vessel CAD (AUC = 0.51, p = 0.83). During the follow-up period 4 cardiovascular deaths (1.9%) occurred in the cohort of CAD patients with vitamin D deficiency and none in the group of subjects with vitamin D sufficiency. Fisher's exact test revealed no significant difference in the occurrence of the primary end point between subjects with vitamin D deficiency and sufficiency (p = 0.47). The composite secondary end point occurred in 24% of the subjects with vitamin D deficiency and in 7% of the subjects with vitamin D sufficiency. After adjustment for multiple confounders and known cardiovascular risk factors we found that vitamin D deficiency have seven times increased hazard (HR = 7.24, 95%CI: 0.99–53.47, p =0.05) for the occurrence of secondary end point compared to subjects with vitamin D sufficiency independently of confounders such as age, gender, kidney function, the presence of dyslipidemia, arterial hypertension, diabetes mellitus, smoking habits, obesity and the severity of CAD (Fig. 1 panel b). Our findings indicate that subjects with vitamin D deficiency had adverse outcome independently of the severity of CAD and other established cardiovascular risk factors. Vitamin D deficiency is highly prevalent in subjects with classic cardiovascular risk factors and in subjects with CAD [2,6]. Moreover data from the Framingham Offspring study and from the Intermountain Healthcare System have shown that in healthy subjects and in individuals with different cardiovascular risk factors low vitamin D levels are associated with the development of coronary atherosclerosis and of symptomatic CAD [4,7]. In addition vitamin D has a pivotal role in regulating calcium homeostasis. Calcium metabolism has also an established role in atherosclerosis and in CAD progression while coronary calcium deposition can be used to evaluate the severity of CAD [1,8]. Accordingly, the hypothesis that vitamin D levels may be associated with the severity of CAD has been generated. Our results have not confirmed the aforementioned hypothesis as we have not found a relationship of vitamin D serum levels with severity of CAD, evaluated with Gensini score. Furthermore, vitamin D deficiency is associated with increased overall and cardiovascular mortality in healthy individuals or subjects with cardiovascular risk factors [4,9]. Our results reveal the negative predictive value of vitamin D deficiency in the cardiovascular outcome of a population with established CAD. Importantly, the negative predictive value of vitamin D deficiency in our cohort of CAD patients was independent of classic cardiovascular risk factors such as age, obesity, renal function, severity of CAD etc. Based on these results the hypothesis that vitamin D status can be used as an additive prognostic factor in CAD patients can be stated here. Further interventional studies are needed to confirm this hypothesis and to define if treatment of vitamin D deficiency can affect cardiovascular outcome in CAD patients.
Letters to the Editor
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. References [1] Tousoulis D, Siasos G, Maniatis K, et al. Novel biomarkers assessing the calcium deposition in coronary artery disease. Curr Med Chem 2012;19:901–20. [2] Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911–30. [3] Martins D, Wolf M, Pan D, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2007;167:1159–65.
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[4] Anderson JL, May HT, Horne BD, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol 2010;106:963–8. [5] Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 2007;167:1730–7. [6] Lavie CJ, Lee JH, Milani RV. Vitamin D and cardiovascular disease will it live up to its hype? J Am Coll Cardiol 2011;58:1547–56. [7] Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008;117:503–11. [8] Tousoulis D, Siasos G, Maniatis K, et al. Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease. Int J Cardiol 2013;167(5):1924–8. [9] Dobnig H, Pilz S, Scharnagl H, et al. Independent association of low serum 25hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med 2008;168:1340–9.
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.06.151
Hemodynamic effects in patients with atrial fibrillation submitted to electrical cardioversion Cristina Giglioli a, Martina Nesti a,⁎, Emanuele Cecchi a, Daniele Landi a, Marco Chiostri b, Gian Franco Gensini b, Valentina Spini a, Salvatore Mario Romano b a b
Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Department of Experimental and Clinical Medicine, Unit Internal Medicine and Cardiology, University of Florence, Viale Morgagni, 85, Florence, Italy
a r t i c l e
i n f o
Article history: Received 12 May 2013 Accepted 30 June 2013 Available online 24 July 2013 Keywords: Atrial fibrillation Electrical cardioversion Hemodynamic Minimal invasive monitoring
Atrial fibrillation (AF) with persistent tachycardia can have a negative impact on left ventricular (LV) function. The rate-control of this arrhythmia may reverse tachycardia-mediated ventricular dysfunction [1]. Previous studies have shown that, when the ventricular rhythm is regular by means of ablate and pace, cardiac output (CO) appears to be higher [2] but this increase has never been demonstrated after electrical cardioversion (ECV) and restoration of sinus rhythm. The aim of our study was to evaluate the hemodynamic changes acutely determined by ECV in AF-patients using a minimally invasive hemodynamic monitoring system (Pressure Recording Analytical Method-PRAM) [3]. We enrolled 26 patients (20 males; 71.9 ± 11.5 years old), admitted to the Cardiac Step-Down Unity (University of Florence, Italy), with a diagnosis of permanent AF and submitted to ECV. At baseline LV ejection fraction was 47.7 ± 13.3% and heart rate (HR) 92 ± 16 bpm. The overall population (GO) was then divided into two groups based on HR: group 1 (G1) consisted of 15 patients with HR ≥ 90 bpm, and group 2 (G2) of 11 patients with HR b 90 bpm.
⁎ Corresponding author at: Department of Heart and Vessels, Azienda OspedalieroUniversitaria Careggi, Viale Morgagni, 85 I - 50134 Florence, Italy. Tel.: +39 0557949577; fax: +39 0557947617. E-mail address: [email protected] (M. Nesti).
After intravenous propofol administration (0.5–1 mg/kg), during spontaneous breathing, a biphasic single R waves synchronized shock, between 100 and 200 Joules on the basis of body weight, was delivered by an external defibrillator. Following radial artery cannulation, PRAM monitoring (MostCare, Vytech, Padova, Italy) was started 5-min before the induction of anesthesia. The hemodynamic variables obtained beat-by-beat were: systolic (SAP), diastolic (DAP), dicrotic (DicAP), and mean arterial blood pressure (MAP); HR; CO; stroke volume (SV); dP/dtmax; [4] cardiac cycle efficiency (CCE); [5,6] and systemic vascular resistance (SVR). Hemodynamic data from each patient were evaluated for average heart beats recorded in 1 min at baseline = T0, 15-min = T2 and 24-h after ECV = T3. Values are reported as means ± SD. Statistical significance was fixed at a two-tailed P level b 0.05. Comparisons were performed, by means of paired samples Student's t-test, within each group between values at T0, T2 and T3. Comparisons between the two groups were obtained with an unpaired t-test. The statistical power (beta, with a two-tailed alpha error b 0.05) was computed between all groups. Changes in hemodynamic variables and statistical results are listed in Table 1. The trend of results and statistical significance between each phases (GO group) is shown in Fig. 1. The main findings of our study were that all groups showed an increase in SV and CCE and a reduction of SVR 24-h after ECV with respect to baseline. Previous studies [7,8] showed an increase in SV and CO after ECV, but these parameters were obtained by means of the thermodilution method which is invasive and time-consuming. Moreover, because of hemodynamic instability during FA, CO measurement hasn't a high reliability [9]. We analyzed the hemodynamic changes with PRAM method, that required only a radial artery cannulation [3]. In terms of SV we detected a significant increase in this parameter 15-min after ECV (T2) in G2 and 24-h after ECV (T3) in G1, and in both
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Vitamin D serum levels are associated with cardiovascular outcome in coronary artery disease Gerasimos Siasos 1, Dimitris Tousoulis ⁎,1, Evangelos Oikonomou, Konstantinos Maniatis, Stamatios Kioufis, Eleni Kokkou, Antigoni Miliou, Marina Zaromitidou, Eva Kassi, Christodoulos Stefanadis 1st Cardiology Department, University of Athens Medical School, “Hippokration” Hospital, Athens, Greece
a r t i c l e
i n f o
Article history: Received 15 May 2013 Accepted 30 June 2013 Available online 26 July 2013 Keywords: Atherosclerosis Coronary artery disease Vitamin D
Coronary artery disease (CAD) is a leading cause of death in western world. Several cardiovascular risk factors such as age, gender, diabetes mellitus, hyperlipidemia, have been recognized and are associated with atherosclerosis progression and adverse prognosis. Recently, the impact of calcium metabolism in the progression of CAD has emerged [1]. Vitamin D has a pivotal role in regulating calcium homeostasis and vitamin D deficiency is now recognized as a situation highly prevalent worldwide. Moreover, low levels of vitamin D are associated with the presence of classic cardiovascular risk factors such as age, obesity,
diabetes mellitus, metabolic syndrome and chronic kidney disease [2,3]. Furthermore, vitamin D deficiency is associated with the presence of subclinical cardiovascular disease, including carotid intima-media thickness, coronary artery calcification and endothelial dysfunction and with overall mortality and cardiovascular risk [4,5]. In the present study we evaluated the diagnostic and prognostic significance of vitamin D status in subjects with established CAD. We consecutively enrolled 252 subjects with CAD. All subjects were treated according to revascularization guidelines with percutaneous coronary intervention and they were followed-up from 3 to 36 months with a median time of 15 months. CAD was defined by coronary angiography as narrowing of more than 50% of at least one major coronary artery. Coronary angiographies were interpreted by at least two experienced cardiologists. On the basis of these coronary angiographies, the number of affected coronary arteries was determined. The severity of CAD was further evaluated by Gensini score and we consider as patients with severe CAD those with a Gensini score more than 80. The baseline characteristics of CAD patients are presented in Table 1. All measurements, in this study were made by the same observer who
Table 1 Characteristics of the study population according to vitamin D status.
Age (years) Male/Female (%) Body mass index (kg/m2) Serum creatinine (mg/dl) Creatinine clearance (ml/min) Hypertension (%) Systolic arterial pressure (mmHg) Diastolic arterial pressure (mmHg) Diabetes mellitus (%) Serum glucose (mg/dl) Dyslipidemia (%) Total cholesterol (mg/dl) Current smokers (%) B blockers (%) ACE inhibitor (%) Angiotensin-receptor blocker (%) Statin (%) Anticoagulants (%) Calcium channel blockers (%) Anti-diabetic medications (%) Vitamin D levels (ng/ml) Gensini score CAD One vessel disease (%) Two vessels disease (%) Three vessels disease (%)
Total study population
Subjects with vitamin D deficiency (88%)
Subjects with vitamin D sufficiency (12%)
P value
62 ± 11 91 28.30 ± 3.70 0.98 ± 0.22 82 ± 18 69 126.4 ± 16.8 78 ± 11 25 113 ± 46 73 159 ± 41 21 73 35 32 86 6 16 22 17.45 (12.51, 24.65) 37 (21, 56)
62 ± 11 88/96 28.37 ± 3.78 0.98 ± 0.23 80 ± 18 67 127 ± 17 78 ± 11 26 114 ± 46 74 159 ± 38 21 75 34 33 87 6 17 22 16.40 (12.08, 21.62) 37(20, 56)
59 ± 9 12/4 28.12 ± 3.26 0.92 ± 0.14 86 ± 15 81 124 ± 19 79 ± 8 21 108 ± 45 69 154 ± 59 21 69 48 24 79 7 10 24 34.80 (31.10, 37,10) 32(24, 62)
0.24 0.25 0.74 0.15 0.10 0.10 0.40 0.59 0.54 0.53 0.59 0.48 0.96 0.49 0.12 0.32 0.27 0.75 0.36 0.78 b 0.001 0.92 0.56
42 34 24
41 35 24
50 25 25
Normally distributed variables are presented as mean ± standard deviation. Skewed variables are presented as median with first and third quartile. Categorical variables are presented as valid percentages. Chi square test was used for categorical variables, t-test for continuous variables normally distributed and Mann-Whitney U test for not normally distributed continuous variables. P values refer to the difference between Subjects with vitamin D deficiency and sufficiency.
⁎ Corresponding author at: Vas. Sophias 114 str, 115 28, Athens, Greece. Tel.: +30 213 2088099; fax: +30 213 2088676. E-mail address: [email protected] (D. Tousoulis). 1 The first two authors (G.S., D.T.) equally contributed in this study.
4446
Letters to the Editor
Fig. 1. Caption: The association of Vitamin D levels with CAD extent and outcome.Panel A: Box-plots of vitamin D levels for subjects with one, two or three vessels coronary artery disease.Panel B: Kaplan–Meier survival curves for the rate of occurrence of the secondary end point in subjects with vitamin D deficiency and sufficiency.
was unaware of the disease status and treatment condition of the participants. Subjects with low ejection fraction (EF b 50%, as estimated by echocardiography), valvulopathies, acute coronary syndromes or myocardial infarction in the last 6 months, chronic kidney disease with creatinine clearance less than 60 ml/min, comorbidities such as malignancies, or with immunological diseases, hyperparathyroidism or hypercalcemia and subjects receiving systemic glucocorticoids, immunosuppressants, or vitamin D or calcium supplementation were excluded from the study. A fasting venous blood sample was obtained in the morning before coronary angiography. Venous blood samples were centrifuged at 3000 rpm and serum/plasma was collected and stored at −80 °C until assayed. Measures for 25(OH)D were performed in samples that had not been previously thawed, using the sensitive method of Liquid Chromatography Mass Spectrometry/Mass Spectrometry (LC-MS/MS) technology (API 5000 System, Applied Biosystems). The lower limit of quantification was 0.3 ng/ml for 25(OH)D. Subjects with vitamin D levels above 30 ng/ml were characterized as having sufficiency and subjects with vitamin D levels below 30 ng/ml were characterized as having deficiency [6]. Lipids and glucose levels were measured by using commercially enzymatic method. Subjects with CAD were evaluated prospectively up to 36 months. The primary end point was the cardiovascular death and the secondary end point was the composite of death from cardiovas-
cular causes, nonfatal myocardial infarction, nonfatal stroke or hospitalization for cardiovascular causes including stroke, severe recurrent cardiac ischemia, recurrent cardiac ischemia, transient ischemic attack, or other arterial thrombotic event. All statistical calculations were performed using SPSS software (version 18.0; SPSS, Chicago, IL). There was no difference in the baseline characteristics between subjects with vitamin D deficiency and sufficiency as it is shown in Table 1. Spearman's rho coefficient revealed no correlation of Gensini score with vitamin D levels (rho = 0.06, p = 0.36). Accordingly, Kruskal–Wallis test revealed no association of vitamin D levels with the severity of CAD. Therefore, for one, two and three vessels disease the median values of vitamin D with first and third quartile were (17.75 (11.37–23.53) vs. 18.40 (13.65–23.53) vs. 16.90 (12.97– 26.50) ng/ml, p = 0.96) respectively (Fig. 1 panel a). To test the diagnostic accuracy of increased vitamin D levels to detect the presence of severe CAD we perform ROC curve analysis. Vitamin D values had no significant diagnostic ability to diagnose severe CAD as it can be estimated by a Gensini score more than 80 (AUC =0.53, p = 0.52) or by the presence of two or three vessel CAD (AUC = 0.51, p = 0.83). During the follow-up period 4 cardiovascular deaths (1.9%) occurred in the cohort of CAD patients with vitamin D deficiency and none in the group of subjects with vitamin D sufficiency. Fisher's exact test revealed no significant difference in the occurrence of the primary end point between subjects with vitamin D deficiency and sufficiency (p = 0.47). The composite secondary end point occurred in 24% of the subjects with vitamin D deficiency and in 7% of the subjects with vitamin D sufficiency. After adjustment for multiple confounders and known cardiovascular risk factors we found that vitamin D deficiency have seven times increased hazard (HR = 7.24, 95%CI: 0.99–53.47, p =0.05) for the occurrence of secondary end point compared to subjects with vitamin D sufficiency independently of confounders such as age, gender, kidney function, the presence of dyslipidemia, arterial hypertension, diabetes mellitus, smoking habits, obesity and the severity of CAD (Fig. 1 panel b). Our findings indicate that subjects with vitamin D deficiency had adverse outcome independently of the severity of CAD and other established cardiovascular risk factors. Vitamin D deficiency is highly prevalent in subjects with classic cardiovascular risk factors and in subjects with CAD [2,6]. Moreover data from the Framingham Offspring study and from the Intermountain Healthcare System have shown that in healthy subjects and in individuals with different cardiovascular risk factors low vitamin D levels are associated with the development of coronary atherosclerosis and of symptomatic CAD [4,7]. In addition vitamin D has a pivotal role in regulating calcium homeostasis. Calcium metabolism has also an established role in atherosclerosis and in CAD progression while coronary calcium deposition can be used to evaluate the severity of CAD [1,8]. Accordingly, the hypothesis that vitamin D levels may be associated with the severity of CAD has been generated. Our results have not confirmed the aforementioned hypothesis as we have not found a relationship of vitamin D serum levels with severity of CAD, evaluated with Gensini score. Furthermore, vitamin D deficiency is associated with increased overall and cardiovascular mortality in healthy individuals or subjects with cardiovascular risk factors [4,9]. Our results reveal the negative predictive value of vitamin D deficiency in the cardiovascular outcome of a population with established CAD. Importantly, the negative predictive value of vitamin D deficiency in our cohort of CAD patients was independent of classic cardiovascular risk factors such as age, obesity, renal function, severity of CAD etc. Based on these results the hypothesis that vitamin D status can be used as an additive prognostic factor in CAD patients can be stated here. Further interventional studies are needed to confirm this hypothesis and to define if treatment of vitamin D deficiency can affect cardiovascular outcome in CAD patients.
Letters to the Editor
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. References [1] Tousoulis D, Siasos G, Maniatis K, et al. Novel biomarkers assessing the calcium deposition in coronary artery disease. Curr Med Chem 2012;19:901–20. [2] Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911–30. [3] Martins D, Wolf M, Pan D, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2007;167:1159–65.
4447
[4] Anderson JL, May HT, Horne BD, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol 2010;106:963–8. [5] Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 2007;167:1730–7. [6] Lavie CJ, Lee JH, Milani RV. Vitamin D and cardiovascular disease will it live up to its hype? J Am Coll Cardiol 2011;58:1547–56. [7] Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008;117:503–11. [8] Tousoulis D, Siasos G, Maniatis K, et al. Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease. Int J Cardiol 2013;167(5):1924–8. [9] Dobnig H, Pilz S, Scharnagl H, et al. Independent association of low serum 25hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med 2008;168:1340–9.
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.06.151
Hemodynamic effects in patients with atrial fibrillation submitted to electrical cardioversion Cristina Giglioli a, Martina Nesti a,⁎, Emanuele Cecchi a, Daniele Landi a, Marco Chiostri b, Gian Franco Gensini b, Valentina Spini a, Salvatore Mario Romano b a b
Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Department of Experimental and Clinical Medicine, Unit Internal Medicine and Cardiology, University of Florence, Viale Morgagni, 85, Florence, Italy
a r t i c l e
i n f o
Article history: Received 12 May 2013 Accepted 30 June 2013 Available online 24 July 2013 Keywords: Atrial fibrillation Electrical cardioversion Hemodynamic Minimal invasive monitoring
Atrial fibrillation (AF) with persistent tachycardia can have a negative impact on left ventricular (LV) function. The rate-control of this arrhythmia may reverse tachycardia-mediated ventricular dysfunction [1]. Previous studies have shown that, when the ventricular rhythm is regular by means of ablate and pace, cardiac output (CO) appears to be higher [2] but this increase has never been demonstrated after electrical cardioversion (ECV) and restoration of sinus rhythm. The aim of our study was to evaluate the hemodynamic changes acutely determined by ECV in AF-patients using a minimally invasive hemodynamic monitoring system (Pressure Recording Analytical Method-PRAM) [3]. We enrolled 26 patients (20 males; 71.9 ± 11.5 years old), admitted to the Cardiac Step-Down Unity (University of Florence, Italy), with a diagnosis of permanent AF and submitted to ECV. At baseline LV ejection fraction was 47.7 ± 13.3% and heart rate (HR) 92 ± 16 bpm. The overall population (GO) was then divided into two groups based on HR: group 1 (G1) consisted of 15 patients with HR ≥ 90 bpm, and group 2 (G2) of 11 patients with HR b 90 bpm.
⁎ Corresponding author at: Department of Heart and Vessels, Azienda OspedalieroUniversitaria Careggi, Viale Morgagni, 85 I - 50134 Florence, Italy. Tel.: +39 0557949577; fax: +39 0557947617. E-mail address: [email protected] (M. Nesti).
After intravenous propofol administration (0.5–1 mg/kg), during spontaneous breathing, a biphasic single R waves synchronized shock, between 100 and 200 Joules on the basis of body weight, was delivered by an external defibrillator. Following radial artery cannulation, PRAM monitoring (MostCare, Vytech, Padova, Italy) was started 5-min before the induction of anesthesia. The hemodynamic variables obtained beat-by-beat were: systolic (SAP), diastolic (DAP), dicrotic (DicAP), and mean arterial blood pressure (MAP); HR; CO; stroke volume (SV); dP/dtmax; [4] cardiac cycle efficiency (CCE); [5,6] and systemic vascular resistance (SVR). Hemodynamic data from each patient were evaluated for average heart beats recorded in 1 min at baseline = T0, 15-min = T2 and 24-h after ECV = T3. Values are reported as means ± SD. Statistical significance was fixed at a two-tailed P level b 0.05. Comparisons were performed, by means of paired samples Student's t-test, within each group between values at T0, T2 and T3. Comparisons between the two groups were obtained with an unpaired t-test. The statistical power (beta, with a two-tailed alpha error b 0.05) was computed between all groups. Changes in hemodynamic variables and statistical results are listed in Table 1. The trend of results and statistical significance between each phases (GO group) is shown in Fig. 1. The main findings of our study were that all groups showed an increase in SV and CCE and a reduction of SVR 24-h after ECV with respect to baseline. Previous studies [7,8] showed an increase in SV and CO after ECV, but these parameters were obtained by means of the thermodilution method which is invasive and time-consuming. Moreover, because of hemodynamic instability during FA, CO measurement hasn't a high reliability [9]. We analyzed the hemodynamic changes with PRAM method, that required only a radial artery cannulation [3]. In terms of SV we detected a significant increase in this parameter 15-min after ECV (T2) in G2 and 24-h after ECV (T3) in G1, and in both