Objective. The aim of this study was to determine the effect of vitamin D supplementation on improving mood (depression and anxiety) and health status (mental and physical) in women with type 2 diabetes mellitus (T2DM). Methods. Fifty women with T2DM and significant depressive symptomology were enrolled into the “Sunshine Study,” where weekly vitamin D supplementation (ergocalciferol, 50,000 IU) was given to all participants for six months. The main outcomes included (1) depression (Center for Epidemiologic Studies Depression, CES-D, and Patient Health Questionnaire, PHQ-9), (2) anxiety (State-Trait Anxiety), and (3) health status (Short Form, SF-12). Results. Forty-six women (92%) completed all visits. There was a significant decrease in depression (CES-D and PHQ-9, p<0.001) and anxiety (state and trait, p<0.001). An improvement in mental health status (SF-12, p<0.001) was also found. After controlling for covariates (race, season of enrollment, baseline vitamin D, baseline depression (PHQ-9), and body mass index), the decline in depression remained significant (CES-D, p<0.001). There was a trend for a better response to supplementation for women who were not taking medications for mood (antidepressants or anxiolytics) (p=0.07). Conclusions. Randomized trials to confirm that vitamin D supplementation can improve mood and health status in T2DM women are needed.

Diabetes is a leading cause of cardiovascular disease. Persons with diabetes are at greater risk for early cardiac mortality, and for repeat events if they survive their first cardiac event. Recently, low serum concentrations of vitamin D have been associated with increased risk for cardiac events. Evidence indicates that persons with diabetes have lower serum concentrations of vitamin D. In addition, persons at risk for diabetes or metabolic syndrome have inadequate serum concentrations of vitamin D. This review will assess the evidence relative to the impact of vitamin D in the development of diabetes, metabolic syndrome, and diabetes complications. Studies that address vitamin D and its impact on metabolic outcomes as well as possible mechanisms of action are provided. Finally, the assessment and suggested treatment for vitamin D deficiency is addressed. Effective detection and treatment of inadequate vitamin D concentrations in persons with diabetes or those at risk for diabetes may be an easy and cost-effective therapy which could improve their longterm health outcomes as well as their quality of life. P roper nutrition is one of the most challenging issues for persons with diabetes. To be successful in the treatment of their disease and in the prevention of long-term complications, a diet that meets the daily requirements and is also satisfying to the individual is optimal. However, sometimes diet alone may not be sufficient for adequate intake of certain nutrients. Recently, vitamin D has sparked widespread interest because of its potential health benefits. Previously, research on vitamin D as it related to health outcomes was limited to persons with cancer and osteoporosis. Recently, however, its impact on other chronic illness has been examined. Some information on vitamin D deficiency and the development Sue Penckofer, PhD, RN JoAnne Kouba, PhD, RD, LDN

Diabetes is a leading cause of cardiovascular disease. Persons with diabetes are at greater risk for early cardiac mortality, and for repeat events if they survive their first cardiac event. Recently, low serum concentrations of vitamin D have been associated with increased risk for cardiac events. Evidence indicates that persons with diabetes have lower serum concentrations of vitamin D. In addition, persons at risk for diabetes or metabolic syndrome have inadequate serum concentrations of vitamin D. This review will assess the evidence relative to the impact of vitamin D in the development of diabetes, metabolic syndrome, and diabetes complications. Studies that address vitamin D and its impact on metabolic outcomes as well as possible mechanisms of action are provided. Finally, the assessment and suggested treatment for vitamin D deficiency is addressed. Effective detection and treatment of inadequate vitamin D concentrations in persons with diabetes or those at risk for diabetes may be an easy and cost-effective therapy which could improve their long-term health outcomes as well as their quality of life.

In past decades, the primary focus on vitamin D was the recognition and treatment of deficiency as it related to metabolic bone disease (rickets, osteomalacia, and secondary hyperparathyroidism). In the last 10 years, however, with the discovery of vitamin D receptors in multiple tissue types has come the recognition that the role of vitamin D extends beyond the musculoskeletal system.1 The presence of abundant vitamin D receptors in myocardial tissue and vasculature and the observation that hypertension may be ameliorated with vitamin D suggest a greater role for vitamin D in the cardiovascular system.2 Presently, large numbers of people are found to have hypovitaminosis D (a term chosen for this review to indicate any concentration below normal under substrate-saturated conditions) resulting in part from more indoor activities and the purposeful avoidance of sunshine. This review first describes why vitamin D, parathyroid hormone (PTH), and the skeleton are important to the heart and vasculature, then outlines why the epidemic of hypovitaminosis D deserves further scrutiny by the cardiovascular community, and finally suggests why treatment options for reducing hypovitaminosis D may favorably affect the morbidity and mortality of common cardiovascular disorders. Vitamin D is both a nutrient and a hormone. It is an essential precursor of calcitriol, 1,25-hydroxyvitamin D3 [1,25(OH)2D], which is necessary for bone development, growth, and mineralization and the maintenance of skeletal integrity. A cascade of steps is needed to cause progression of lesser active nutritionally ingested or synthesized vitamin D to more biologically active forms as depicted in Figure 1.1 The cascade starts with the photolysis of 7 dehydrocholesterol in the epidermis by solar ultraviolet B (UVB) radiation to previtamin D3, which then undergoes thermal isomerization to vitamin D3. Vitamin D3 undergoes primary hydroxylation in the liver to 25-hydroxyvitamin D [25(OH)D] and then …

Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated adverse reaction to heparin therapy. To evaluate clinical outcomes and effects of argatroban therapy in acutely ill HIT patients. Retrospective analysis. Hospital in-patient. Acutely ill patients with clinically diagnosed HIT from previous multicenter, historically controlled studies of argatroban therapy in HIT. Argatroban, adjusted to maintain activated partial thromboplastin times 1.5 to 3 times baseline, or historical control therapy (ie, no direct thrombin inhibition). We identified 488 patients who received argatroban (N = 390; mean dose of 1.9 µg/kg/min for a mean 6 days) or historical control therapy (N = 98) for HIT. The primary all-cause composite endpoint of death, amputation, or new thrombosis within 37 days occurred in 133 (34.1%) argatroban-treated patients and 38 (38.8%) controls ( P = .41). Argatroban, versus control, significantly reduced the primary thrombosis-related composite endpoint of death because of thrombosis, amputation secondary to ischemic complications of HIT, or new thrombosis (17.7% vs 30.6%, P = .007). Significant reductions also occurred in new thrombosis and death because of thrombosis. Major bleeding was similar between groups (7.7% vs 8.2%; P = .84). Adverse outcomes were more likely to occur in patients who were initially diagnosed with HIT and thrombosis, had undergone cardiac surgery, were not white, or had more severe thrombocytopenia. In acutely ill HIT patients, argatroban, versus historical control, provides effective antithrombotic therapy without increasing major bleeding. Patients with more severe thrombocytopenia or HIT-related thrombosis on HIT diagnosis have a poorer prognosis, emphasizing the importance of prompt recognition/ treatment of HIT in acutely ill patients.

HomeCirculationVol. 116, No. 3Letter by Wallis and Penckofer Regarding Article, “Calcium/Vitamin D Supplementation and Cardiovascular Events” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Wallis and Penckofer Regarding Article, “Calcium/Vitamin D Supplementation and Cardiovascular Events” Diane E. Wallis, MD Sue Penckofer, PhD, RN Diane E. WallisDiane E. Wallis Midwest Heart Specialists, Downers Grove, Ill Search for more papers by this author Sue PenckoferSue Penckofer Professor and Loyola Faculty Scholar, Loyola University Chicago, School of Nursing, Maywood, Ill Search for more papers by this author Originally published17 Jul 2007https://doi.org/10.1161/CIRCULATIONAHA.107.707539Circulation. 2007;116:e86To the Editor:We read with interest the article by Dr Hsia and colleagues.1 We concur that the null finding was primarily caused by inadequate replacement. Dietary vitamin D supplements were never meant to replace the daily requirements needed to achieve the physiological levels of 25-hydroxyvitamin D levels (>40 ng/mL).2 There is little assurance that over-the-counter vitamin D supplements are biologically active or even contain what the package labeling asserts. Age- or drug-induced hypochlorhydria may interfere with the absorption of calcium-complexed supplements.3 There is evidence that approximately half of patients who take supplements remain severely deficient in vitamin D.4States of calcium and vitamin D deficiency are also associated with changes in parathyroid hormone, the counterregulatory hormone. Hyperparathyroidism, regardless of whether it is primary or secondary, has been causally linked to increased cardiovascular morbidity and mortality, hypertension, hypertensive heart disease diastolic dysfunction, myocardial fibrosis, and calcification of the aortic valve and annulus.5 In our opinion, no conclusions can be drawn on lack of efficacy of vitamin D replacement without evidence that maximal parathyroid hormone suppression has occurred and that adequate calcium absorption is present (24-hour urinary calcium levels of 100 to 300 mg/d).6 We have found no studies where “treat to target” has been performed. Thus, we believe that it is important to complete studies that use adequate vitamin D and calcium replacement and demonstrate normalization of parathyroid hormone before it can be concluded that such therapy is ineffective.DisclosuresNone.1 Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, Heckbert SR, Johnson KC, Manson JE, Sidney S, Trevisan M; for the Women’s Health Initiative Investigators. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007; 115: 846–854.LinkGoogle Scholar2 Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999; 69: 842–856.CrossrefMedlineGoogle Scholar3 Yang YU, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006; 296: 2947–2953.CrossrefMedlineGoogle Scholar4 Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. Hypovitaminosis D in medical inpatients. NEJM. 1998; 338: 777–783.CrossrefMedlineGoogle Scholar5 Symons C, Fortune F, Greenbaum RA, Dandona P. Cardiac hypertrophy, hypertrophic cardiomyopathy, and hyperparathyroidism: an association. Br Heart J. 1985; 54: 539–542.CrossrefMedlineGoogle Scholar6 Steingrimsdottir L, Gunnarsson O, Indridason OS, Franzson L, Sigurdsson G. Relationship between serum parathyroid hormone levels, vitamin D sufficiency and calcium intake. JAMA. 2005; 294: 2336–2341.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Veloudi P, Jones G and Sharman J (2016) Effectiveness of Vitamin D Supplementation for Cardiovascular Health Outcomes, Pulse, 10.1159/000452742, 4:4, (193-207), . Lakatta E, Maltsev V and Vinogradova T (2010) A Coupled SYSTEM of Intracellular Ca2+ Clocks and Surface Membrane Voltage Clocks Controls the Timekeeping Mechanism of the Heart’s Pacemaker, Circulation Research, 106:4, (659-673), Online publication date: 5-Mar-2010. Doorenbos C, van den Born J, Navis G and de Borst M (2009) Possible renoprotection by vitamin D in chronic renal disease: beyond mineral metabolism, Nature Reviews Nephrology, 10.1038/nrneph.2009.185, 5:12, (691-700), Online publication date: 1-Dec-2009. Pilz S, Dobnig H, Nijpels G, Heine R, Stehouwer C, Snijder M, van Dam R and Dekker J (2009) Vitamin D and mortality in older men and women, Clinical Endocrinology, 10.1111/j.1365-2265.2009.03548.x, 71:5, (666-672), Online publication date: 1-Nov-2009. Maltsev V and Lakatta E (2009) Synergism of coupled subsarcolemmal Ca 2+ clocks and sarcolemmal voltage clocks confers robust and flexible pacemaker function in a novel pacemaker cell model , American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.01118.2008, 296:3, (H594-H615), Online publication date: 1-Mar-2009. Wallis D, Penckofer S and Sizemore G (2008) The “Sunshine Deficit” and Cardiovascular Disease, Circulation, 118:14, (1476-1485), Online publication date: 30-Sep-2008. July 17, 2007Vol 116, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.107.707539PMID: 17638936 Originally publishedJuly 17, 2007 PDF download Advertisement SubjectsTreatment

Heparin-induced thrombocytopenia (HIT), and heparin-induced thrombocytopenia with thrombosis syndrome (HITTS), are immune-mediated complications of heparin therapy associated with significant morbidity and mortality. Although much has been learned about the pathophysiology of this syndrome, there are many difficult issues remaining for physicians involved in the daily care of the patient about the diagnosis, prevention, and treatment. To determine whether the earliest detection of HIT and heparin cessation impacted outcome, 116 consecutive patients at a single institution, with HIT diagnosed by platelet aggregometry, were divided into groups by time to heparin cessation based on daily platelet counts. Thrombocytopenia was defined in two ways: as a 50% decline from baseline and an absolute platelet count of less than 100x10(9)/L. The overall thrombosis rate was 39% and was predominantly venous. The mortality rate of 27% was similar in patients with both HIT and HITTS. Despite heparin cessation at less than 48 h from the onset of thrombocytopenia (mean 0.5 days), there were no differences in thrombosis or mortality when compared to patients with later heparin cessation (mean 4.3 days). In summary, early detection of HIT with heparin cessation is insufficient therapy for the management and treatment of HITTS. An alternative to this strategy in the treatment of patients with HIT is indicated.

Heparin-induced thrombocytopenia is one of the most difficult problems facing clinicians today. Despite recent understanding of the pathophysiology of this disorder, there are many unresolved issues about diagnosis, prevention, and treatment. In this article, difficulties physicians encounter when faced with a suspected heparin-induced thrombocytopenia patient will be reviewed as well as our experience in 113 patients with heparin-induced thrombocytopenia which highlights the failure of current preventive strategies for heparin-induced thrombocytopenia. The experience of using warfarin in 51 patients with heparin-induced thrombocytopenia will also be reviewed.

Management of Heparin-Induced Thrombocytopenia and Heparin-Induced Thrombocytopenia and Thrombosis Syndrome

Mitral leaflets which appear abnormally thick by transthoracicecho predict an adverse prognosis in pts with mitral valve prolapse (MVP). While it is known from pathologic studies that the valve tissue in such pts is both redundant and abnormally thick, the echocardiographic appearance of increased thickness may result from a combination of overlap of redundant tissue and intrinsic increases in leaflet thickness. Transesophagealecho (TEE) affords the opportunity to more precisely characterize the morphology of the mitral leaflets in these patients. Accordingly, twenty-two pts [11 with MVP (defined as superior displacement of the mitral leaflets above the mitral annulus on the parasternal long axis view of the transthoracic echo and increased diastolic width of the anterior mitral leaflet) and 11 controls (CTRL)] prospectively underwent detailed TEE examination to quantify mitral leaflet thickness. Since systolic tensing of the closed mitral leaflets minimizes tissue overlap, systolic leaflet width was used to measure intrinsic tissue thickness. In contrast, the width of the relatively slack mitral leaflets in diastole represents a combination of both leaflet overlap and intrinsic tissue thickness. Blinded TEE measurements of leaflet width demonstrated greater diastolicwidth of both anterior (0.64±0.20 v. 0.30±0.04 em, p&lt;0.001) and posterior (0.67±0.39 v. 0.31±0.06 em, p &lt; 0.01) leaflets in MVP compared to CTRL. In contrast systolicwidth of the anterior (0,22±0.05 v, 0.20±0.04 em, NS) and posterior (0.25±0.07 v. 0.24±0.05 em, NS) leaflets were similar in MVP and CTRL. Fractional change in leaflet width from diastole to systole (%ΔW=[(diastolic width) - (systolic Width)]×100/[diastolic width]) was measured as an index of the change in leaflet overlap between diastole and systole, %LΔW was significantly greater for both anterior (62±13 v. 34±16%, p&lt;0.001) and posterior (54±19 v. 22±21%, p&lt;0.005) leaflets in MVP compared to CTRL.

While transesophageal echocardiography (TEE) provides detailed structural information about the mitral valve, the range of normal systolic displacement of the mitral leaflets and the best criteria for diagnosing mitral valve prolapse (MVP) by this technique remain controversial. The area subtended by the systolic displacement of the mitral leaflets into the left atrium beyond the annular hinge points on 4 chamber and 2 chamber images of the mitral valve was measured by TEE in a blinded prospective study of 11 MVP pts (who had systolic displacement of the mitral leaflets superior to the mitral annular plane on parasternal long axis images by transthoracic echo and click and/or late systolic murmur on physical exam) and 11 NORMAL subjects (who had no evidence for MVP by either transthoracic echo or exam).

Two cases are presented where patients underwent surgery for the removal of relatively small intracardiac masses detected by echocardiography, but whose differential diagnosis was uncertain. In 1 case, the mass was hypertrophied atrial muscle, while in the other case, it was mitral annulus thrombus.

Esmolol is a rapidly metabolized cardioselective β-adrenergic blocker that provides steady state β-adrenergic blockade when administered by continuous intravenous infusion. To determine the efficacy of esmolol in the management of unstable angina, 23 patients with known coronary artery disease, who averaged 3.7 ± 2.7 daily episodes of chest pain at rest, were randomized to receive either a continuous infusion of esmolol (n = 12) or oral propranolol (n = 11), as an adjunct to concomitant antianginal therapy. Patients with systolic blood pressure <110 mm Hg, heart rate <60 beats/min or known contraindications to β blockade were excluded. Esmolol was titrated in a step-wise fashion from 2 to 24 mg/min at 5-minute intervals up to a 30% reduction in heart rate and systolic blood pressure double-product. The propranolol dose was increased every 6 hours by 50 to 100% to achieve a similar reduction in heart rate and blood pressure. When compared with their 24-hour baseline periods, both groups achieved a significant reduction in episodes of chest pain, from 4.6 ± 3.3 to 1.4 ± 1.5 in the esmolol group (p < 0.02) and 2.6 ± 1.4 to 1.0 ± 1.5 in the propranolol group (p < 0.02) during the subsequent study period. The cardiac event rate and incidence of drug side effects were similar between the 2 groups; however, side effects seen with esmolol did not require treatment after drug discontinuation. Thus, maximally tolerated β blockade is an effective therapy for unstable angina. Potential advantages of a continuous infusion of esmolol are the ability to titrate to therapeutic endpoints and the safety afforded by its ultrashort half-life.

O'CONNELL, JOHN B.; COSTANZO-NORDIN, MARIA ROSA; SUBRAMANIAN, RAMIAH; ROBINSON, JOHN A.; WALLIS, DIANE E.; SCANLON, PATRICK J.; GUNNAR, ROLF M.Author Information

Dilated cardiomyopathy is a heterogeneous group of disorders with a prognosis that is dependent upon the severity of presenting clinical and hemodynamic abnormalties. Although this condition is characterized by a high mortality, spontaneous improvement is noted in 25% of cases. Standard therapeutic modalities are nonspecific and consist of the therapy of congestive heart failure and ventricular arrhythmia. Recent studies suggest that beta blockade and cardiac transplantation may soon become accepted modalities in this condition. Acute viral myocarditis is a common disease that has a good prognosis, however occasionally progression to chronic myocardial disease has been identified. The therapy of acute viral myocarditis should be limited to symptomatic treatment, anticoagulation, and bed rest. When chronic myocarditis is identified on endomyocardial biopsy in patients with heart failure of unknown cause, the treatment differs little from that of dilated cardiomyopathy with the exception that recognizing that efficacy has not been proven; immunosuppressive therapy may be added in life-threatening situations. Future studies will be directed at further clarification of the prognosis of each of these conditions with intensive evaluation of the role of beta blockade and immunosuppression.