We examined the prevalence of cardiac and cerebrovascular disease among hospitalized patients with and without multiple sclerosis (MS).
This study used the Statewide Planning and Research Cooperate System data set of over 15 million hospitalizations in New York City from 1988 through 2002. We identified MS patients 40-84 years of age who were hospitalized for reasons other than MS or related complications. MS patients were matched 1:2 on age, gender, race/ethnicity, and insurance. Outcomes included a principal discharge diagnosis of ischemic heart disease [International Classification of Diseases, Ninth Revision (ICD-9) 410-414], myocardial infarction (ICD-9 410), and ischemic stroke (ICD-9 434, 436). Multivariate logistic regression was used to compare vascular disease outcomes in MS and non-MS patients controlling for demographic and clinical factors.
Our study included 9,949 hospitalizations among MS patients and 19,898 hospitalizations for matched non-MS controls. MS patients were less likely to be hospitalized for ischemic heart disease (OR = 0.58, 95% CI = 0.51-0.66) or myocardial infarction (OR = 0.78, 95% CI = 0.64-0.96), but more likely to be hospitalized for ischemic stroke (OR = 1.66, 95% CI = 1.33-2.09) than matched non-MS controls.
MS patients have decreased rates of hospital admission for ischemic heart disease and myocardial infarction, but increased rates of hospitalization for ischemic stroke as compared to the general non-MS population.
"These abnormalities are diagnosed e.g. by imaging techniques (magnetic resonance, tomography), examination of brain hypoperfusion parameters – CBF (cerebral blood flow), CBV (cerebral blood volume) and VMTT (vascular mean transit time) (Varsik et al. 2004a). Many authors have published these findings: 1. a higher risk of ischaemic diseases development – cardiovascular brain stroke in MS patients (Allen et al. 2008; Christiansen et al. 2010), 2. a decrease of cerebral perfusion in MS patients (Inglese et al. 2007; Law et al. 2004), 3. a reduced venous blood drainage from the brain and the upper part of the spinal cord (Zamboni et al. 2009). "
[Show abstract][Hide abstract] ABSTRACT: There is about 30% higher risk of the myocardial infarction in patients diagnosed with multiple sclerosis (MS) than in people without MS. Increased risk of cardiovascular disease development positively correlates with levels of serum markers of an endothelial dysfunction, and may give rise to a global cerebral hypoperfusion. It appears that these complications precede progressive loss of axons, which mechanisms are complex and should be linked to a loss of β2 adrenergic receptors on astrocytes of demyelinating lesions. Consequence of this deficiency, the cause of which is not known yet, is a decline in energy metabolism of axons. Moreover, the loss of these receptors is linked to a reduced redistribution of potassium ions by astrocytes, glutamate excitotoxicity and increase of calcium ion concentration in the axon with subsequent activation of necrotic processes. In addition to immunological aspects we should take into account also parameters of the functional state of endothelium when appropriate targeted therapy for patient is considered.
"In New York city, persons with MS aged 40–84 years were less likely to be hospitalized for IHD (OR 0.58, 95% CI: = 0.51– 0.66) or MI (OR 0.78, 95% CI: = 0.64–0.96) than matched hospital controls (Allen et al., 2008). Hospitalized elderly Medicare patients with MS had reported fewer hospital discharges for IHD than hospitalized persons without MS (Fleming and Blake, 1994). "
[Show abstract][Hide abstract] ABSTRACT: Background
Studies suggest an altered risk of ischemic heart disease (IHD) in multiple sclerosis (MS), but data are limited. We aimed to validate and apply administrative case definitions to estimate the incidence and prevalence of IHD in MS.
Using administrative data we identified persons with incident MS (MSPOP) and a matched general population (GPOP) cohort. We developed case definitions for IHD using ICD-9/10 codes and prescription claims, compared them to medical records, then applied them to evaluate the incidence and prevalence of IHD.
Agreement between medical records and the administrative definition using ≥1 hospital or ≥2 physician claims over 5 years was moderate (kappa=0.66; 95% CI: 0.42–0.90). In 2005, the age-standardized prevalence of IHD was 6.77% (95% CI: 5.48–8.07%) in the MSPOP and 6.11% (95% CI: 5.56–6.66%) in the GPOP. The prevalence of IHD was higher in the MSPOP than the GPOP among persons aged 20–44 years (prevalence ratio 1.87; 95% CI: 1.65–2.12) and aged 45–59 years (prevalence ratio 1.21; 95% CI: 1.08–1.35). The incidence of IHD was also higher in the MSPOP (incidence rate ratio 1.24; 95% CI: 0.97–1.59).
More than 5% of the MSPOP has IHD. The incidence of IHD was higher than expected in persons aged <60 years. Further evaluation of this issue is warranted.
Multiple Sclerosis and Related Disorders 10/2013; 2(4):355–361. DOI:10.1016/j.msard.2013.03.001 · 0.88 Impact Factor
"Conversely, a longitudinal cohort study analyzing data from 10,156 patients enrolled in the Consortium of Rheumatology Researchers of North America Rheumatoid Arthritis registry reported that Methotrexate was not associated with a reduced risk of the primary composite cardiovascular endpoint of incident non-fatal myocardial infarction, non-fatal stroke or transient ischemic attack, and cardiovascular-related death . Controversy exists on whether chronic MS is associated with cardiovascular disease, with studies suggesting an association  and others rejecting it [40,41]. The association between Methotrexate and cardiotoxicity observed in RENEW remains speculative since analysis was post-hoc rather than pre-specified. "
[Show abstract][Hide abstract] ABSTRACT: Registry to Evaluate Novantrone Effects in Worsening Multiple Sclerosis (RENEW) was a 5-year, phase IV study in which the safety of Mitoxantrone was monitored in a patient cohort from the United States (US). The objective of the study was to evaluate the long-term safety profile of Mitoxantrone in patients with secondary progressive multiple sclerosis (SPMS), progressive relapsing multiple sclerosis (PRMS), and worsening relapsing-remitting multiple sclerosis (RRMS).
Overall, 509 patients (395 SPMS, 81 worsening RRMS, 33 PRMS) were enrolled and treated at 46 multiple sclerosis (MS) treatment centers located in the US. Patients received Mitoxantrone in accordance with the package insert every 3 months. During the treatment phase, patients received laboratory workups and cardiac monitoring every 3 months and then annually for a total of 5 years.
Five hundred and nine subjects were enrolled in this trial and received at least one infusion of Mitoxantrone. Overall, 172 (33.8%) completed the 5-year trial (i.e., participated for 5 years +/- 3 months [treatment + follow-up]); 337 (66.2%) did not complete the 5-year trial. Annual follow-up data were available for 250 of 509 enrolled patients. Left ventricular ejection fraction reduction under 50% was reported in 27 (5.3%) patients during the treatment phase (n = 509) and 14 (5.6%) patients during the annual follow-up phase (n = 250). Signs and symptoms of congestive heart failure were observed in 10 (2.0%) patients (six during treatment phase and four during the annual follow-up phase). Post-hoc analyses of the risk for cardiotoxicity outcomes revealed that cumulative dose exposure is the primary risk factor associated with the risk of cardiac toxicity with Mitoxantrone. Therapy-related leukemia was reported in three (0.6%) patients who received total cumulative Mitoxantrone doses of 73.5 mg/m2, 107.3 mg/m2, and 97.1 mg/m2 respectively. During the treatment phase, persistent amenorrhea developed in 22% (28/128) of women with regular menses and 51% (25/49) of women with irregular menses at baseline. During the annual follow-up phase, persistent amenorrhea developed in 5% (4/73) of women with regular menses at baseline.
RENEW results are consistent with the known safety profile of Mitoxantrone, and provide additional long-term safety data for Mitoxantrone in MS patients.
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