Marco R. DiTullio

Metabolic Syndrome and Ischemic Stroke Risk Northern Manhattan Study

Background and Purpose— More than 47 million individuals in the United States meet the criteria for the metabolic syndrome. The relation between the metabolic syndrome and stroke risk in multiethnic populations has not been well characterized. Methods— As part of the Northern Manhattan Study, 3298 stroke-free community residents were prospectively followed up for a mean of 6.4 years. The metabolic syndrome was defined according to guidelines established by the National Cholesterol Education Program Adult Treatment Panel III. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs for ischemic stroke and vascular events (ischemic stroke, myocardial infarction, or vascular death). The etiologic fraction estimates the proportion of events attributable to the metabolic syndrome. Results— More than 44% of the cohort had the metabolic syndrome (48% of women vs 38% of men, P<0.0001), which was more prevalent among Hispanics (50%) than whites (39%) or blacks (37%). The metabolic syndrome was associated with increased risk of stroke (HR=1.5; 95% CI, 1.1 to 2.2) and vascular events (HR=1.6; 95% CI, 1.3 to 2.0) after adjustment for sociodemographic and risk factors. The effect of the metabolic syndrome on stroke risk was greater among women (HR=2.0; 95% CI, 1.3 to 3.1) than men (HR=1.1; 95% CI, 0.6 to 1.9) and among Hispanics (HR=2.0; 95% CI, 1.2 to 3.4) compared with blacks and whites. The etiologic fraction estimates suggest that elimination of the metabolic syndrome would result in a 19% reduction in overall stroke, a 30% reduction of stroke in women; and a 35% reduction of stroke among Hispanics. Conclusions— The metabolic syndrome is an important risk factor for ischemic stroke, with differential effects by sex and race/ethnicity.

Age As a Determinant of Adverse Events in Medically Treated Cryptogenic Stroke Patients With Patent Foramen Ovale

Background and Purpose— Patent foramen ovale (PFO) is associated with cryptogenic stroke. There is no study that assessed the effect of age on adverse event rates in cryptogenic stroke patients with PFO. The purpose of this retrospective analysis from PFO in Cryptogenic Stroke Study (PICSS) database was to assess the effect of age on the risk of adverse events in medically treated cryptogenic stroke patients with PFO. Methods— 250 cryptogenic stroke patients from PICSS were followed-up for 24 months, with death and recurrent ischemic stroke as primary endpoints. Hazard ratios were calculated for determination of relative risk in cryptogenic stroke patients with and without PFO in 3 age groups (younger than 55, 55 to 64, and 65 years or older). Results— Among the 2 younger age groups, the presence of PFO did not significantly affect the risk of adverse events (P =0.15; hazard ratio=0.21; 95% CI, 0.02 to 1.78; 2-year event rates, 2.0% versus 9.3%; and P =0.70; hazard ratio=0.72; 95% CI, 0.14 to 3.73; 2-year event rates, 10.0% versus 13.9%). However, in those aged 65 years or older, the risk of adverse events was significantly higher in the patients with PFO (P =0.01; hazard ratio=3.21; 95% CI, 1.33 to 7.75; 2-year event rates 37.9% versus 14.5%). Conclusions— In this exploratory analysis, the presence of PFO in the younger cryptogenic stroke patients did not increase the risk of adverse events. However, in the older patients, PFO significantly increased the risk of adverse events.

Relation between Socioeconomic Status, Race-Ethnicity, and Left Ventricular Mass: The Northern Manhattan Study

Abstract—Increased left ventricular mass (LVM) and lower socioeconomic status (SES) are predictors of cardiovascular morbidity and mortality. Blacks and Hispanics are more likely to have higher LVM and lower SES. The relation between SES, race–ethnicity, and LVM has not been fully explored. Data were used from the NOMAS population-based sample of 1916 subjects living in Northern Manhattan. SES was characterized on the basis of educational attainment and divided into 4 categories. Echocardiography-defined LVM was indexed according to height at the allometric power of 2.7 and analyzed as a continuous variable. LVM varied by race in our cohort (blacks 48.9 g/m2.7, Hispanics 48.4 g/m2.7, whites 45.6 g/m2.7; P =0.004). Using ANCOVA, there was a significant inverse and graded association between mean LVM and SES for the total cohort. Mean LVM was 48.4 g/m2.7, 48.6 g/m2.7, 47.1 g/m2.7, and 45.3 g/m2.7 for the lowest to the highest educational level category (P trend=0.0004). This relationship remained among normotensives (P trend=0.0005) and was present for blacks (P trend=0.009), but not for whites (P trend=0.86) or Hispanics (P trend=0.47). The difference in mean LVM between the highest and lowest categories of education was 5.3 g/m2.7 for blacks, 0.0 g/m2.7 for whites, and 1.0 g/m2.7 for Hispanics. Lower SES is an independent predictor of increased LVM among hypertensive and normotensive blacks.

Effect of parathyroidectomy on subclinical cardiovascular disease in mild primary hyperparathyroidism

OBJECTIVE We recently demonstrated that mild primary hyperparathyroidism (PHPT) is associated with increased carotid intima-media thickness (IMT) and stiffness, and increased aortic valve calcification. It is unclear whether parathyroidectomy (PTX) improves these abnormalities. The purpose of this study was to determine whether cardiovascular abnormalities in PHPT improve with PTX. DESIGN Forty-four patients with PHPT were studied using carotid ultrasound and transthoracic echocardiography before and after PTX. Carotid IMT, carotid plaque and stiffness, left ventricular mass index (LVMI), myocardial and valvular calcification, and diastolic function were measured before, 1- and 2-year post-PTX. RESULTS Two years after PTX, increased carotid stiffness tended to decline to the normal range (17%, P=0.056) while elevated carotid IMT did not improve. Carotid plaque number and thickness, LVMI and cardiac calcifications did not change after PTX, while some measures of diastolic function (isovolumic relaxation time (IVRT) and tissue Doppler peak early diastolic velocity) worsened within the normal range. Indices did improve in patients with cardiovascular abnormalities at baseline. Increased carotid stiffness improved by 28% (P=0.004), a decline likely to be of clinical significance. More limited improvements also occurred in elevated IMT (3%, P=0.017) and abnormal IVRT (13%, P<0.05), a measure of diastolic dysfunction. CONCLUSIONS In mild PHPT, PTX led to modest changes in some cardiovascular indices. Improvements were mainly evident in those with preexisting cardiovascular abnormalities, particularly elevated carotid stiffness. These findings are reassuring with regard to current international guidelines that do not include cardiovascular disease as a criterion for PTX.

Race-ethnic differences in the association between lipid profile components and risk of myocardial infarction: The Northern Manhattan Study

OBJECTIVE The aim of this study was to explore race-ethnic differences in the association between plasma lipid components and risk of incident myocardial infarction (MI). DESIGN/METHODS As part of the Northern Manhattan Study, 2,738 community residents without cardiovascular disease were prospectively evaluated. Baseline fasting blood samples were collected, and lipid panel components were analyzed as continuous and categorical variables. Cox proportional hazards models were used to calculate HRs and 95% CIs for incident MI after adjusting for demographic and cardiovascular risk factors. RESULTS The mean age was 68.8 ± 10.4 years; 36.7% were men. Of the participants, 19.9% were non-Hispanic white; 24.9%, non-Hispanic black; and 52.8%, Hispanic (>80% from the Caribbean). Hispanics had lower mean high-density lipoprotein cholesterol (HDL-C) and higher triglycerides (TG)/HDL-C. During a mean 8.9 years of follow-up, there were 163 incident MIs. In the whole cohort, all lipid profile components were associated with risk of MI in the expected directions. However, HDL-C (adjusted HR per 10 mg/dL increase 0.93, 95% CI 0.76-1.12) and TG/HDL-C >2 (adjusted HR 0.89, 95% CI 0.51-1.55) were not predictive of MI among Hispanics but were predictive among non-Hispanic blacks and whites. Triglycerides/HDL-C per unit increase was associated with an 8% higher risk of MI among Hispanics (adjusted HR 1.08, 95% CI 1.04-1.12). CONCLUSIONS In Hispanics, low HDL-C and TG/HDL-C >2 were not associated with MI risk. Our data suggest that a different TG/HDL ratio cutoff may be needed among Hispanics to predict MI risk.

Variability of right ventricular functional recovery after lung transplantation

BACKGROUND The purpose of this study was to assess by echocardiography the effects of lung transplantation on recovery of right ventricular (RV) function in patients with preoperative RV dysfunction. METHODS Fourteen (20%) of 71 lung transplant recipients were identified by echocardiography as manifesting abnormal RV function before lung transplantation. These 14 patients were selected for follow-up echocardiographic study 8 months after transplantation. RESULTS RV function improved significantly in the study group. Mean RV end-diastolic area decreased from 26.8 +/- 7.9 cm2 to 20.1 +/- 4.7 cm2 (P < 0.01); mean RV end-systolic area decreased from 21.5 +/- 6.8 cm2 to 13.1 +/- 4.2 (P < 0.01); and mean RV fractional area change (FAC) increased from 20.4 +/- 3.3% to 35.8 +/- 8.9% (P < 0.001). A subgroup of four patients, however, exhibited no change in RV function. Patients who achieved improvement in RV function tended to be younger, had shorter duration of disease before transplantation, and had higher pulmonary arterial (PA) pressures before transplantation (PA systolic, 89 +/- 28 mmHg vs. 38 +/- 11 mmHg, P < 0.001; PA diastolic, 42 +/- 11 mmHg vs. 19 +/- 3 mmHg, P < 0.002). Each of the eight patients with primary pulmonary hypertension exhibited improvement in RV function (mean delta FAC +20.6 +/- 5.9%), while two of three patients with emphysema and both patients with idiopathic pulmonary fibrosis failed to achieve improvement in RV function (mean delta FAC +2.3 +/- 1.2%). CONCLUSIONS Improvement of RV function assessed by echocardiography occurs after lung transplantation, even in patients with severe preoperative RV dysfunction. However, the degree of improvement is variable and may depend on the degree of RV after-load reduction and the presence or absence of intrinsic myocardial disease. RV ejection parameters do not distinguish between these two possibilities.

Assessment of endothelium-mediated vasodilation of the peripheral circulation by transcutaneous ultrasonography and venous occlusion plethysmography

SummaryTranscutaneous ultrasonography is a noninvasive technique with the ability to measure the volumetric blood flow of the peripheral circulation. Peripheral blood flow can be determined by highresolution imaging of vessel diameter coupled with Doppler assessment of flow velocity. This method, however, has not been validated in vivo. Accordingly, brachial artery flow in response to intraarterial infusion of vasodilators was assessed by ultrasonography in 16 healthy subjects and compared to values obtained simultaneously by venous occlusion plethysmography. Blood flow calculated from ultrasound-derived vessel diameter and flow velocity was found to highly correlate with plethysmographic flow, withr values ranging from 0.83 to 0.99. Using this ultrasound technique combined with plethysmography, the response of conduit and resistance vessels to endothelium-mediated vasodilation was characterized. Doppler velocity rose dramatically with endothelium-dependent acetylcholine (970%), but only modestly with endothelium-independent vasodilators, nitroglycerin (292%) and nitroprusside (340%). Despite eliciting the greatest overall forearm flow response, acetylcholine resulted in a smaller increase in conduit diameter (15.4%) than nitroglycerin (21.8%), and only a comparable change than nitroprusside (14.6%). Taken together, these results suggest that acetylcholine acts predominantly on resistance vessels, whereas nitrovasodilators affect mainly conduit vessels. In summary, transcutaneous ultrasonography can be used reliably to assess flow changes in the peripheral circulation. Combined with plethysmography, this technique is useful for determining the relative contribution of conduit and resistance vessels to peripheral flow, particularly in the assessment of endothelium-mediated vasodilation.

Lack of Effect of Estrogen on Rest and Treadmill Exercise in Postmenopausal Women Without Known Cardiac Disease

To assess the peripheral vascular effects of estrogen in women without coronary disease, normal postmenopausal women (mean age 56 +/- 8 years) participated in a randomized, crossover trial using treadmill exercise echocardiography, and received oral conjugated estrogen, 0.625 mg/day or underwent a drug-free period. There was no significant effect on heart rate, blood pressure, double product, left ventricular end-systolic and end-diastolic diameters, or electrocardiographic measures after estrogen. In contrast to the profound effects reported in patients with cardiac disease, oral estrogen in normal women does not bestow significant benefit on treadmill exercise echocardiographic variables at rest or during modest levels of exercise.

Ethnic differences in aortic valve thickness and related clinical factors.

BACKGROUND Prior studies suggest that the causes of calcific aortic valve (AV) disease involve chronic inflammation, lipoprotein levels, and calcium metabolism, all of which may differ among race-ethnic groups. We sought to determine whether AV thickness differs by race-ethnicity in a large multiethnic population-based cohort. METHODS The Northern Manhattan Study includes stroke-free community-based Hispanic (57%), non-Hispanic black (22%), and non-Hispanic white (21%) participants. The relation between AV thickness on transthoracic echocardiography and clinical risk factors for atherosclerosis was evaluated among 2,085 participants using polytomous logistic regression models. Aortic valve thickness was graded in 3 categories (normal, mild, and moderate/severe) based on leaflet thickening and calcification. RESULTS Mild AV thickness was present in 44.4% and moderate/severe thickness in 5.7% of the cohort, with the lowest frequency of moderate/severe thickness seen particularly among Hispanic women. In multivariate models adjusting for age, sex, race-ethnicity, body mass index, hypertension, coronary artery disease, blood glucose, and high-density lipoprotein cholesterol, Hispanics had significantly less moderate/severe AV thickness (odds ratio 0.43, 95% CI 0.25-0.73) than non-Hispanic whites. Men were almost 2-fold as likely to have moderate/severe AV thickness compared with women (odds ratio 1.96, 95% CI 1.24-3.10). CONCLUSIONS In this large multiethnic population-based cohort, there were ethnic differences in the degree of AV thickness. Hispanic ethnicity was strongly protective against AV thickness. This effect was not related to traditional risk factors, suggesting that unmeasured factors related to Hispanic ethnicity and AV thickness may be responsible.

Spontaneous Resolution of Pulmonary Venous Thrombosis After Lung Transplantation

Thrombus formation at the pulmonary venous anastomotic site after lung transplantation may have catastrophic consequences, including allograft failure and stroke. However, treatment with systemic anticoagulation may facilitate bleeding in the early postoperative period. In the present report, we describe the clinical and transesophageal echocardiographic findings of pulmonary venous thrombosis in two patients in the immediate postoperative period after lung transplantation. Treatment with systemic anticoagulation was not feasible because of extensive postoperative thoracic bleeding in each instance. A conservative approach was taken on the basis of the small size of each thrombus and lack of accelerated flow velocity at the site of the thrombus. Each thrombus resolved spontaneously without clinical sequelae. These two cases suggest that thrombus size and flow velocity at the anastomotic site may be used to guide the clinical management of pulmonary venous thrombosis after lung transplantation.