Matan Rothschild

Associations between Serum 25-hydroxyvitamin D and Lipids, Lipoprotein Cholesterols, and Homocysteine.

Background: Serum 25(OH) vitamin D levels are inversely associated with cardiovascular disease (CVD) mortality, mediated in part by independent positive relationships with high-density lipoprotein cholesterol (HDLC) and inverse relationships with low-density lipoprotein cholesterol (LDLC), triglyceride, and homocysteine. Aims: In this study, we assessed relationships between fasting serum vitamin D and lipids, lipoprotein cholesterols, and homocysteine. Materials and Methods: We studied 1534 patients sequentially referred to our center from 2007 to 2016. Fasting serum total 25(OH) vitamin D, plasma cholesterol, triglyceride, HDLC, LDLC, and homocysteine were measured. Stepwise regression models were used with total cholesterol, triglyceride, HDLC, LDLC, and homocysteine as dependent variables and explanatory variables age, race, gender, body mass index (BMI), and serum vitamin D levels. Relationships between quintiles of serum vitamin D and triglycerides, HDLC, LDLC, and homocysteine were assessed after covariance adjusting for age, race, gender, and BMI. Results: Fasting serum vitamin D was positively correlated with age, HDLC, and White race, and was inversely correlated with BMI, total and LDL cholesterol, triglyceride, and fasting serum homocysteine (P ≤ 0.0001 for all). Serum vitamin D was a significant independent inverse explanatory variable for total cholesterol, triglyceride, and LDL cholesterol, and accounted for the largest amount of variance in serum total cholesterol (partial R 2 =3.6%), triglyceride (partial R 2 =3.1%), and LDLC (partial R 2 =2.9%) (P < 0.0001 for all). Serum vitamin D was a significant positive explanatory variable for HDLC (partial R 2 =1.4%, P < 0.0001), and a significant inverse explanatory variable for homocysteine (partial R 2 = 6.0-12.6%). Conclusions: In hyperlipidemic patients, serum vitamin D was a significant independent inverse determinant of total cholesterol, LDLC, triglyceride, and homocysteine, and a significant independent positive determinant of HDLC. Thus, serum vitamin D might be protective against CVD.

Pathognomonic Palmar Crease Xanthomas of Apolipoprotein E2 Homozygosity-Familial Dysbetalipoproteinemia

Pathognomonic Palmar Crease Xanthomas of Apolipoprotein E2 Homozygosity-Familial Dysbetalipoproteinemia It is important for all clinicians, especially dermatologists, to recognize the rare diagnostic physical sign of familial dysbetalipoproteinemia (FD), palmar crease xanthoma (PCX),1 because it is an early warning sign to initiate diagnostic tests (apolipoprotein [apoE] genotyping, lipid profiling, documentation of dysbetalipoproteinemia by ultracentrifugation or nuclear magnetic resonance lipid profiling), and thus enables treatment. Familial dysbetalipoproteinemia, a rare familial hyperlipidemia, is very sensitive to treatment with fibrates and/or statins,2 with lipid normalization and reduction in risk of atherosclerotic cardiovascular disease (ASCVD).3 Approximately 20% of patients with FD have characteristic palmar xanthomas.1 Our specific aim was to assess dermatologic manifestations of FD (type 3 hyperlipoproteinemia) with the mutant apoE2/2 genotype, and emphasize the centrality of the dermatologist in a diagnostic-therapeutic role in identifying unique palmar xanthomas.

Hospitalization for pulmonary embolism associated with antecedent testosterone or estrogen therapy in patients found to have familial and acquired thrombophilia

BackgroundIn patients hospitalized over a 4 year period for pulmonary embolism (PE), we assessed relationships of testosterone (TT) and estrogen therapy (ET) anteceding PE in patients found to have familial-acquired thrombophilia.MethodsFrom 2011 through 2014, 347 patients were hospitalized in Cincinnati Mercy Hospitals with PE. Retrospective chart review was used to identify patients receiving TT or ET before PE; coagulation studies were done prospectively if necessary.ResultsPreceding hospitalization for PE, 8 of 154 men (5 %) used TT, and 24 of 193 women (12 %) used ET. The median number of months from the initiation of TT or ET to development of PE was 7 months in men and 18 months in women. Of the 6 men having coagulation measures, all had ≥ 1 thrombophilia, and of the 18 women having measures of coagulation, 16 had ≥ 1 thrombophilia. The sensitivity of a previous history of thrombosis to predict PE was low, 25 % (2/8 men), 4 % (1/24 women).ConclusionsOf 154 men hospitalized for PE, 8 (5 %) used TT, and of 193 women, 24 (12 %) used ET. Our data suggests that PE is an important complication of TT in men and ET in women, in part reflecting an interaction between familial and acquired thrombophilia and exogenous hormone use.

Thrombophilia in 153 Patients With Premature Cardiovascular Disease ≤Age 45

We assessed contributions of thrombophilia to premature cardiovascular disease (CVD) events (≤ age 45) in 153 patients. Test results of thrombophilia–hypofibrinolysis were obtained in 153 patients with CVD ≤ age 45, 110 healthy normal controls, and 110 patients who had venous thromboembolism (VTE) without CVD. Of the 153 patients with CVD, 121 (79%) had sustained myocardial infarction, 70 (46%) had coronary artery stenting, and 53 (35%) had coronary artery bypass grafts. The first CVD events occurred at ages >20 to 35 in 47 patients and at ages >35 to 45 in 106 patients. At study entry, median low-density lipoprotein cholesterol was 126 mg/dL, 56 (37%) smoked, 56 (37%) had hypertension, and 56 (37%) were diabetic. Cases differed from normal controls for high factor VIII (10 [22%] of 45 vs 7 of 103 [7%], P = .007), high homocysteine (32 [21%] of 151 vs 5 [5%] of 107, P = .0002), low free protein S (5 [11%] of 44 vs 2 [2%] of 96, P = .032), high anticardiolipin antibodies (ACLA) IgM (11 [9%] of 129 vs 2 [2%] of 109, P = .024), high lipoprotein (a) [Lp(a)] (46 [30%] of 151 vs 21 [19%] of 110, P = .038), and the lupus anticoagulant (4 [11%] of 37 vs 2 [2%] of 110, P = .035). There were no differences (P > .05) between cases and VTE controls except free protein S and Lp(a). Free protein S was more often low in VTE controls (24 [28%] of 85 vs 5 [11%] of 44, P = .03) and Lp(a) was more often high in cases (46 [30%] of 151, VTE controls 12 [17%] of 71, P = .032). In 153 patients with premature CVD ≤ age 45, thrombophilia was pervasive (high factor VIII, homocysteine, ACLA IgM, low free protein S, high Lp(a), and lupus anticoagulant), evidencing thrombotic contribution to premature CVD. Moreover, thrombophilia in patients with premature CVD was comparable to VTE controls, emphasizing the pervasive nature of thrombophilia in premature CVD.

Progressively Worsening Premature Coronary Artery Disease: Adding Anticoagulation Stabilizes–Reverses Clinical Symptomatic Disease Progression in Thrombophilic–Atherothrombotic Patients: A Pilot Study

In 35 patients with 116 severe premature cardiovascular disease (CVD) events (median age: 48 years), 14 having worsening CVD despite maximal intervention, we evaluated thrombophilia and speculated that anticoagulation might arrest–reverse progressive thrombophilic–atherothrombotic CVD. Thrombophilia–hypofibrinolysis in the 35 patients was compared to 110 patients with venous thromboembolism (VTE) without CVD and to 110 healthy normal controls. Efficacy–safety of anticoagulation was prospectively assessed in 14 of the 35 patients whose CVD worsened over 2 years despite maximal medical–surgical intervention. At entry on maximally tolerated lipid-lowering therapy, median low-density lipoprotein was 88 mg/dL. Measures of thrombophilia–hypofibrinolysis in the 35 cases differed from 110 VTE controls only for the lupus anticoagulant, present in 6 (21%) of 28 cases versus 4 (4%) of 91 VTE controls (P = .01), and for high anticardiolipin antibodies (ACLAs) immunoglobulin G, 5 (14%) of 35 cases versus 4 of 108 VTE controls (4%), P = .04. The 14 patients who were anticoagulated differed from 110 VTE controls only for the lupus anticoagulant, 38% versus 4%, P = .001, and for high lipoprotein (a), 46% versus 17%, P = .028, respectively. The 14 patients with atherothrombosis having inexorably worsening CAD despite maximal medical–surgical therapy were anticoagulated for 6.5 years (median), with clinical CVD progression arrested in 12 (86%), and all 12 became asymptomatic. In the 35 patients with premature CVD, thrombophilia was pervasive, comparable to or more severe than in VTE controls without CVD. When CVD progressively worsens despite maximal intervention, thrombophilia and atherosclerosis (atherothrombosis) are commonly concurrent, and the downhill course of CVD may be arrested–stabilized by anticoagulation.

ID: 20: HOSPITALIZATION FOR PULMONARY EMBOLISM ASSOCIATED WITH ANTECEDENT TESTOSTERONE OR ESTROGEN THERAPY IN PATIENTS FOUND TO HAVE FAMILIAL THROMBOPHILIA

Background In patients hospitalized over a 4 year period for pulmonary embolism (PE), and subsequently found to have familial-acquired thrombophilia, we assessed relationships of thrombophilia with testosterone (TT) and estrogen therapy (ET) anteceding PE. Methods From 2011 through 2014, 347 patients were hospitalized in Cincinnati Mercy Hospitals with PE. Retrospective chart review was used to document TT or ET anteceding PE in patients subsequently found to have familial or acquired thrombophilia. Results Preceding hospitalization for PE, of the 154 men and 193 women, 8 men (5% of men) used TT, 24 women (12% of women) used ET (16 birth control pills, 6 hormone replacement therapy, 2 progesterone). Median age in the 8 men was 56 and for the 24 women 38. After excluding 45 women with cancer preceding PE, 24 of 148 (16%) women with PE had used ET, and after excluding 33 men with cancer, 8/121 men (7%) used TT. Of these 8 men, 6 used TT gels, 50 mg/day, and 2 had intra muscular TT 50 mg/week. Of the 8 men, 5 (63%) smoked, 2 had a history of thrombotic events, and 2 had type 2 diabetes. The median number of months from the initiation of TT to development of PE was 7 months. Coagulation evaluations were done in 6 of the 8 men. All 6 had ≥1 thrombophilia; 1 heterozygous for the G20210A prothrombin gene (PTG) mutation, 1 with high factor VIII, 3 with high homocysteine (1 of whom had MTHFR C677T homozygosity), 2 with low protein C, 2 with low protein S, and 2 with low free protein S. Two of 8 men had Klinefelters syndrome. Of the 24 women, 2 were diabetic, 1 had a history of thrombosis, and 7 (29%) smoked. The median time between initiation of ET and the PE was 18 months. In 18 out of the 24 women, coagulation evaluations were performed. 15 had ≥1 thrombophilia; 4 were factor V Leiden heterozygotes, 1 PTG heterozygote, 2 high Factor VIII, 1 high Factor XI, 2 with the lupus anticoagulant, 3 low protein S, 2 low Free S, 3 low antithrombin III, 3 high anticardiolipin antibodies. Conclusion After excluding antecedent cancer, 24/148 women (16%) had ET before PE, and TT was taken by 8/121 (7%) men. PE is an important complication of TT in men and ET in women, in part reflecting an interaction between familial and acquired thrombophilia and exogenous hormone use.