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Hylton V Joffe

Publications and source records attributed to Hylton V Joffe.

8 recordsLinked to original sources
PubMed2005

Sex hormone-binding globulin and serum testosterone are inversely associated with C-reactive protein levels in postmenopausal women at high risk for cardiovascular disease.

PURPOSE: C-reactive protein (CRP), androgens, and menopausal loss of endogenous estrogens are associated with cardiovascular disease (CVD). We hypothesized that high androgens, low estradiol, and low sex hormone-binding globulin (SHBG) would be associated with high CRP in postmenopausal women. METHODS: CRP, SHBG, estradiol, and total testosterone were measured using baseline bloods of 221 hormone therapy (HT)-nonusers and 162 HT-users from a cross-sectional analysis in a nested case-control sample of the Women's Health Study. Hormones and CRP were ln-transformed and relationships were assessed with Spearman correlations and linear regression. RESULTS: ln-SHBG (beta=-0.40; p<0.01) and ln-testosterone (beta=-0.24; p=0.04) were the only independent hormonal predictors of ln-CRP among HT-nonusers after adjusting for age, hypertension, smoking, body mass index, diabetes, exercise, HDL cholesterol, alcohol intake, and CVD occurrence during follow-up. Upon stratification, the association between ln-SHBG and ln-CRP persisted among HT nonusers who subsequently developed CVD (beta=-0.55; p=0.01), but not among women who remained CVD-free (p=0.28). The inverse relationship between ln-SHBG and ln-CRP was strongest among the leanest women. None of the sex-hormones predicted ln-CRP among HT-users. CONCLUSIONS: SHBG and total testosterone were inversely associated with CRP among HT nonusers in this study. The relationship between SHBG and CRP was more strongly inverse among leaner women.

Aged↗
PubMed2005

Effect of aldosterone and mineralocorticoid receptor blockade on vascular inflammation.

Aldosterone, the final product of the renin-angiotensin-aldosterone system, is classically viewed as a regulator of renal sodium and potassium handling, blood volume, and blood pressure. Recent studies suggest that aldosterone can cause microvascular damage, vascular inflammation, oxidative stress and endothelial dysfunction. In animal models, aldosterone-mediated vascular injury in the brain, heart, and kidneys leads to stroke, myocardial injury, and proteinuria. These effects may be modified by dietary salt intake; aldosterone-mediated vascular damage is increased in susceptible animals fed a high-salt diet compared to a low-salt diet despite lower plasma aldosterone levels on the high-salt diet. In humans, there is a growing literature supporting the adverse effects of aldosterone in heart failure, hypertension, left ventricular hypertrophy, and renal disease. Aldosterone receptor antagonists are beneficial even in patients on angiotensin converting enzyme inhibitors and attenuate aldosterone-mediated vascular injury by mechanisms that appear to be independent of changes in systolic blood pressure. This review focuses on the adverse effects of aldosterone on the vascular system and describes our current understanding of the underlying mechanisms for this injury.

Aldosterone↗
PubMed2005

Few predictors of massive deep vein thrombosis.

Factors that predispose to thrombus propagation from the femoropopliteal veins to the pelvic veins are poorly understood. Our goal was to determine whether there are characteristics that identify patients with massive deep vein thrombosis (DVT). We compared the 122 (2.5%) patients presenting with massive DVT (pelvic plus lower-extremity DVT) to the 4,674 (97.5%) patients with isolated lower-extremity DVT from a prospective United States multicenter DVT registry. Patients with massive DVT were younger (59.4+/-18.9 years vs. 64.3+/-16.8 years; p<0.01), less likely to have hypertension (40% vs. 51%; p=0.02), and more likely to smoke (21% vs. 13%; p=0.02) and have ongoing radiation therapy (7% vs. 3%; p=0.02). The massive DVT group more commonly presented with extremity edema (80% vs. 69%; p<0.01) and erythema (21% vs. 12%; p<0.01) than the isolated lower-extremity DVT group. However, after multivariable logistic regression analysis, extremity erythema (adjusted odds ratio 1.86; 95% CI 1.13-3.04) was the only independent sequela of massive DVT and younger age (adjusted odds ratio 1.17 per decreasing decade of age; 95% confidence interval: 1.02-1.34) was the only independent predictor of massive DVT. Thrombus propagation from the femoropopliteal system cannot be reliably predicted using demographic or clinical characteristics.

Adult↗
PubMed2004

Upper-extremity deep vein thrombosis: a prospective registry of 592 patients.

BACKGROUND: Upper-extremity deep vein thrombosis (UEDVT) occurs spontaneously or sometimes develops as a complication of pacemaker use, long-term use of a central venous catheter (CVC), or cancer. METHODS AND RESULTS: To improve our understanding of UEDVT, we compared the demographics, symptoms, risk factors, prophylaxis, and initial management of 324 (6%) patients with central venous catheter (CVC)-associated UEDVT, 268 (5%) patients with non-CVC-associated UEDVT, and 4796 (89%) patients with lower-extremity DVT from a prospective US multicenter DVT registry. The non-CVC-associated UEDVT patients were younger (59.2+/-18.2 versus 64.2+/-16.9 years old; P<0.0001), less often white (65% versus 73%; P<0.01), leaner (body mass index [BMI] 26.8+/-7.1 versus 28.5+/-7.3 kg/m2; P<0.001), and more likely to smoke (19% versus 13%; P=0.02) than the lower-extremity DVT patients. By way of propensity analysis and multivariable logistic regression analysis, we determined that an indwelling CVC was the strongest independent predictor of UEDVT (odds ratio [OR], 7.3; 95% confidence interval [CI], 5.8 to 9.2). An age of <67 years, a BMI of <25 kg/m2, and hospitalization were the independent predictors of non-CVC-associated UEDVT. Most (68%) UEDVT patients were evaluated while they were inpatients. Only 20% of the 378 UEDVT patients who did not have an obvious contraindication to anticoagulation received prophylaxis at the time of diagnosis. CONCLUSIONS: UEDVT risk factors differ from the conventional risk factors for lower-extremity DVT. Our findings identify deficiencies in our current understanding and the prophylaxis of UEDVT and generate hypotheses for future research efforts.

Adolescent↗
PubMed2004

Warfarin dosing and cytochrome P450 2C9 polymorphisms.

Two cytochrome P450 2C9 (CYP2C9) polymorphisms, CYP2C9*2 and *3, metabolize warfarin inefficiently. We assessed the extent to which these polymorphisms explain very low warfarin dose requirements and hemorrhagic complications after excluding non-genetic determinants of warfarin dosing. In this retrospective observational study, 73 patients with stable warfarin doses for > or =1 month and International Normalized Ratios (INR) of 2.0-3.0 were enrolled from our Anticoagulation Clinic. Seventeen patients required < or =2 mg (low-dose), 41 required 4-6 mg (moderate-dose), and 15 required > or =10 mg (high-dose) of daily warfarin. CYP2C9 genotyping was assessed by PCR amplification and restriction enzyme digestion analysis of DNA isolated from circulating leukocytes. The CYP2C9 polymorphisms independently predicted low warfarin requirements after adjusting for Body Mass Index, age, acetaminophen use, and race (OR 24.80; 95% CI 3.83-160.78). At least one polymorphism was present in every patient requiring < or =1.5 mg of daily warfarin, and 88%, 37%, and 7% of the low-, moderate-, and high-dose groups, respectively. All homozygotes and compound-heterozygotes for the variant alleles were in the low-dose group. Rates of excessive (INR>6.0) anticoagulation (and bleeding) were 4.5 (6.0), 7.9 (7.9), and 14.7 (0) per 100 patient-years in the wild-types, heterozygotes, and compound heterozygotes/homozygotes, respectively. In conclusion, CYP2C9*2 or *3 compound heterozygotes and homozygotes have low warfarin requirements even after excluding liver disease, excessive alcohol or acetaminophen consumption, low body weight, advancing age, and drug interactions. These polymorphisms increase the rate of excessive anticoagulation, but this risk does not appear to be associated with higher bleeding rates when anticoagulation status is closely monitored.

Adult↗
PubMed2002

Laboratory thrombophilias and venous thromboembolism.

Inherited abnormalities of coagulation are increasingly recognized in patients with venous thromboembolism. Common causes of hypercoagulability, also known as thrombophilia, include factor V Leiden, the prothrombin gene mutation, hyperhomocysteinemia, and antiphospholipid antibodies. Thrombophilia should be suspected in patients who develop idiopathic venous thromboembolism at a young age, recurrent thrombosis, thromboses at unusual sites, recurrent unexplained pregnancy loss, or if there is a family history of thrombotic disorders. The most cost-effective approach is to initially screen for factor V Leiden, the prothrombin gene mutation, hyperhomocysteinemia, and antiphospholipid antibodies because these are the most common defects causing thrombophilia. Long-term anticoagulation is controversial but should be considered if unprovoked venous thromboembolism recurs.

Humans↗