969-99 Biocompatible Mechanical Left Ventricular Support: Potential Alternative to Transplantation

Use of mechanical circulatory support has been limited by its associated bleeding and thrombotic complications. Blood contact with an artificial surface results in a well-deined pattern of hematologic alterations. The TCI HeartMate® left ventricular assist device (LVAD) is an implantable circulatory support pump currently used as a bridge to transplantation. Its textured blood contacting surfaces result in a formation of an adherent pseudoneointimal lining which eliminates the direct interaction of blood elements with the artificial surface. To determine if this biological lining could mitigate the stereotypical blood-synthetic surface interactions, we studied eight patients who underwent implantation at our institution over a 10 month period from 5/93 to 3/94. Seven of the 8 patients were bridged to transplantation. Three patients were transplanted within 10 days and one month data could not be obtained. Hemodynamic and hemostatic parameters (mean±sd) were studied as follows:Pre-implantPOD 7POD 28Cardiac index (I/min/m2)1.8±0.73.2±0.43.1±0.5Systolic BP (mmHg)759±6.8125.8±9.7130.4±8.1Hemoglobin (mg/dl)7.4±1.88.2±1.69.6±2.0Plasma free hemoglobin (mg/dl)15.4±1.76.4±2.36.8±1.9Prothrombin time (sec)14.2±1.113.4±0.713.3±0.7Partial thromboplastin time (sec)56.7±15.931.8±4.837.6±11.9Platelet count (× 103lcu mm)250±81269±63325±37In vitro platelet reactivity to the agonist ADP remained normal pre and post implantation. Average perioperative blood requirements included PRBC, 3.3±1.3 units; platelets, 2.3±4.5 units; fresh frozen plasma, 2±1.9 units. No blood products were required after postoperative day 2.We conclude that TCI LVAD support improves hemodynamics and can bridge patients in pre-implant cardiogenic shock to transplantation. Furthermore, no red cell destruction or hemostatic and thrombotic complications were observed despite one month of support without anticoagulation therapy. Therefore, as the donor shortage continues, LVADs with biocompatible surfaces may provide an alternative to cardiac transplantation

Eating Pattern Response to a Low-Fat Diet Intervention and Cardiovascular Outcomes in Normotensive Women: The Women's Health Initiative.

BackgroundWomen without cardiovascular disease (CVD) or hypertension at baseline assigned to intervention in the Women's Health Initiative Dietary Modification (DM) trial experienced 30% lower risk of coronary heart disease (CHD), whereas results in women with hypertension or prior CVD could have been confounded by postrandomization use of statins.ObjectivesIntervention participants reported various self-selected changes to achieve the 20% total fat goals. Reviewed are intervention compared with comparison group HRs for CHD, stroke, and total CVD in relation to specific dietary changes in normotensive participants.MethodsDietary change was assessed by comparing baseline with year 1 FFQ data in women (n = 10,371) without hypertension or CVD at baseline with intake of total fat above the median to minimize biases due to use of the FFQ in trial eligibility screening.ResultsIntervention participants self-reported compensating reduced energy intake from total fat by increasing carbohydrate and protein. Specifically they increased plant protein, with those in the upper quartile (increased total protein by ≥3.3% of energy) having a CHD HR of 0.39 (95% CI: 0.22, 0.71), compared with 0.92 (95% CI: 0.57, 1.48) for those in the lower quartile of change (decreased total protein ≥0.6% of energy), with P-trend of 0.04. CHD HR did not vary significantly with change in percentage energy from carbohydrate, and stroke HR did not vary significantly with any macronutrient changes. Scores reflecting adherence to recommended dietary patterns including the Dietary Approaches to Stop Hypertension Trial and the Healthy Eating Index showed favorable changes in the intervention group.ConclusionsIntervention group total fat reduction replaced with increased carbohydrate and some protein, especially plant-based protein, was related to lower CHD risk in normotensive women without CVD who reported high baseline total fat intake. This trial was registered at clinicaltrials.gov as NCT00000611. Link to the WHI trial protocol: https://www.whi.org/about/SitePages/Dietary%20Trial.aspx

Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes the strong heart study

AbstractObjectivesThe goal of this study was to determine if the haptoglobin phenotype was predictive of cardiovascular disease (CVD) in diabetic mellitus (DM).BackgroundCardiovascular disease is the most frequent, severe, and costly complication of type 2 DM. There are clear geographic and ethnic differences in the risk of CVD among diabetic patients that cannot be fully explained by differences in conventional CVD risk factors. We have demonstrated that a functional allelic polymorphism in the haptoglobin gene acts as a major determinant of susceptibility for the development of diabetic microvascular complications.MethodsWe sought to determine if this paradigm concerning the haptoglobin gene could be extended to CVD in DM. We tested this hypothesis in a case-control sample from the Strong Heart study, a population-based longitudinal study of CVD in American Indians. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis in 206 CVD cases and 206 matched controls age 45 to 74 years. Median follow-up was six years.ResultsIn multivariate analyses controlling for conventional CVD risk factors, haptoglobin phenotype was a highly statistically significant, independent predictor of CVD in DM. The odds ratio of having CVD in DM with the haptoglobin 2-2 phenotype was 5.0 times greater than in DM with the haptoglobin 1-1 phenotype (p = 0.002). An intermediate risk of CVD was associated with the haptoglobin 2-1 phenotype.ConclusionsThis study suggests that determination of haptoglobin phenotype may contribute to the algorithm used in CVD risk stratification, and in evaluation of new therapies to prevent CVD in the diabetic patient

Depressed Myocardial Energetic Efficiency Increases Risk of Incident Heart Failure: The Strong Heart Study

An estimation of myocardial mechano-energetic efficiency (MEE) per unit of left ventricular (LV) mass (MEEi) can significantly predict composite cardiovascular (CV) events in treated hypertensive patients with normal ejection fraction (EF), after adjustment for LV hypertrophy (LVH). We have tested whether MEEi predicts incident heart failure (HF), after adjustment for LVH, in the population-based cohort of a "Strong Heart Study" (SHS) with normal EF. We included 1,912 SHS participants (age 59 ± 8 years; 64% women) with preserved EF (≥50%) and without prevalent CV disease. MEE was estimated as the ratio of stroke work to the "double product" of heart rate times systolic blood pressure. MEEi was calculated as MEE/LV mass, and analyzed in quartiles. During a follow-up study of 9.2 ± 2.3 years, 126 participants developed HF (7%). HF was preceded by acute myocardial infarction (AMI) in 94 participants. A Kaplan-Meier plot, in quartiles of MEEi, demonstrated significant differences, substantially due to the deviation of the lowest quartile (p < 0.0001). Using AMI as a competing risk event, sequential models of Cox regression for incident HF (including significant confounders), demonstrated that low MEEi predicted incident HF not due to AMI (p = 0.026), after adjustment for significant effect of age, LVH, prolonged LV relaxation, diabetes, and smoking habits with negligible effects for sex, hypertension, antihypertensive therapy, obesity, and hyperlipemia. Low LV mechano-energetic efficiency per unit of LVM, is a predictor of incident, non-AMI related, HF in subjects with initially normal EF

Using HbA1c to improve efficacy of the American Diabetes Association fasting plasma glucose criterion in screening for new type 2 diabetes in American Indians. The Strong Heart Study

WSTĘP. Celem badania jest określenie optymalnej krytycznej linii FPG-HbA1c, umożliwiającej rozpoznanie cukrzycy w grupie chorych z nieprawidłowym stężeniem glukozy na czczo (IFG, impaired fasting glucose) i poprawa skuteczności oznaczenia glikemii na czczo (FPG, fasting plasma glucose), stosowanego jako samodzielne badanie przesiewowe w kierunku cukrzycy u Indian amerykańskich. MATERIAŁ I METODY. Analizowano oznaczenia stężenia glukozy na czczo i 2 godziny po doustnym obciążeniu glukozą (2hPG) oraz HbA1c w grupie 2389 Indian amerykańskich w wieku 45-74 lat, którzy dotychczas nie byli leczeni z powodu cukrzycy, u których wcześniej nie rozpoznawano cukrzycy, a których poddano wyjściowej i powtórnej ocenie w ramach badania SHS (Strong Heart Study). Zgodnie z kryteriami American Diabetes Association cukrzycę rozpoznawano, gdy stężenie glukozy na czczo było równe lub wyższe niż 126 mg/dl lub gdy wartość 2hPG wynosiła 200 mg/dl lub więcej. Nieprawidłowe stężenie glukozy na czczo rozpoznawano, gdy mieściło się ono w przedziale 110 Ł FPG < 126 mg/dl, a jako wartość prawidłową (NFG, normal fasting glucose) przyjęto stężenie glukozy na czczo niższe niż 110 mg/dl. Do rozpoznawania cukrzycy w grupie badanych z IFG (2hPG ł 200 mg/dl) zastosowano modele regresji logistycznej. Najlepszy model wybrano na podstawie porównania pól pod krzywymi ROC (receiver operating characteristic) utworzonymi w oparciu o różne modele regresji logistycznej. Do wyznaczenia optymalnych wartości krytycznych użyto funkcji przydatności opartej na najlepszym modelu oraz współczynniku koszt/korzyść. Dane z drugiego badania wykorzystano do oceny wpływu czasu, jaki upłynął pomiędzy dwoma kolejnymi badaniami przesiewowymi, zarówno na kryterium FPG, jak i na optymalną krytyczną linię FPG-HbA1c. WYNIKI. W grupie chorych z nowo rozpoznaną cukrzycą, u 37% w badaniu wyjściowym oraz u 55,2% w badaniu powtórnym stwierdzono wartości 2hPG większe bądź równe 200 mg/dl, przy wartościach FPG mniejszych niż 126 mg/dl. Zarówno w wyjściowym, jak i w drugim oznaczeniu u znacznej części pacjentów z IFG rozpoznano cukrzycę (odpowiednio: 19,3 i 22,9%). Porównanie pól pod krzywymi ROC dla poszczególnych modeli regresji logistycznej wykazało, że największa wartość pola odpowiada łącznemu oznaczeniu FPG i HbA1c. Wartość ta była znamiennie wyższa od wartości pola dla oznaczenia FPG (p = 0,0008). Dla współczynnika koszt/korzyść = 0,23888 optymalna linia krytyczna o największej użyteczności miała wartość równą 0,89 × HbA1c + 0,11 × FPG = 17,92. U chorych, u których wartości FPG i HbA1c znajdowały się na tej linii lub powyżej, zalecano wykonanie doustnego testu tolerancji glukozy (OGTT, oral glucose tolerance test) w celu rozpoznania lub wykluczenia cukrzycy. Optymalne wartości krytyczne w badaniu powtórzonym po 4 latach były mniejsze. WNIOSKI. Według kryteriów American Diabetes Association cukrzycę rozpoznaje się, gdy wartość FPG jest większa lub równa 126 mg/dl albo gdy wartość 2hPG wynosi 200 mg/dl lub więcej. Wykonanie badania FPG jest proste i zaleca się je jako badanie przesiewowe. Natomiast stosowanie w praktyce OGTT w celu uzyskania wartości 2hPG jest kłopotliwe, szczególnie u chorych, u których stwierdza się wartość FPG poniżej 126 mg/dl. Wykonywanie OGTT jako badania przesiewowego u każdego pacjenta również jest niepraktyczne. Uzyskane dane wskazują, że u 37% osób z nowo wykrytą cukrzycą w badaniu wyjściowym i u 55,2% w oznaczeniu drugim stężenie glukozy w OGTT wynosiło 200 mg/dl lub więcej, podczas gdy wartość FPG była niższa niż 126 mg/dl. W takich wypadkach, na podstawie oznaczenia wyłącznie FPG jako badania przesiewowego, cukrzyca nie zostałaby rozpoznana. Mimo że odsetek chorych na cukrzycę w grupie NFG jest mały i może zostać zignorowany (4,7% w pierwszym i 6,5% w drugim oznaczeniu), to częstość przypadków cukrzycy stwierdzonych w grupie IFG w trakcie niniejszego badania (ok. 20%) wymaga uwzględnienia w dyskusji na temat metody badań przesiewowych. Wydaje się, że u części chorych z nieprawidłowym stężeniem glukozy na czczo, wybranych na podstawie optymalnych krytycznych wartości FPG-HbA1c, warto wykonać OGTT. Wyznaczenie optymalnej linii krytycznej i odstępu między kolejnymi testami przesiewowymi wymaga dalszych badań.INTRODUCTION. To find an optimal critical line in the fasting plasma glucose (FPG)-HbA1c plane for identifying diabetes in participants with impaired fasting glucose (IFG) and thereby improve the efficacy of using FPG alone in diabetes screening among American Indians. RESEARCH DESIGN AND METHODS. We used FPG, 2-h postload glucose (2hPG), and HbA1c measured in the 2,389 American Indians (aged 45&#8211;74 years, without diabetes treatment or prior history of diabetes) in the Strong Heart Study (SHS) baseline (second) examination. Participants were classified as having diabetes if they had either FPG &#163; 126 mg/dl or 2hPG &#8805; 200 mg/dl, as having IFG if they had 110 &#163; FPG < 126 mg/dl, and as having normal fasting glucose (NFG) if they had FPG < 110, according to the American Diabetes Association (ADA) definition. Logistic regression models were used for identifying diabetes (2hPG &#8805; 200 mg/dl) in IFG participants. The areas under the receiver operating characteristic (ROC) curves generated by different logistic regression models were evaluated and compared to select the best model. A utility function based on the best model and the cost-to-benefit ratio was used to find the optimal critical line. The data from the second examination were used to study the effect of the time interval between the successive diabetes screenings on both the FPG criterion and the optimal critical line. RESULTS. A total of 37% of all subjects with new diabetes at baseline and 55.2% of those in the second exam had 2hPG &#8805; 200 but FPG < 126. There was a very large portion of IFG participants with diabetes (19.3 and 22.9% in the baseline and second exam, respectively). Among the areas under the ROC curves, the area generated by the logistic regression model on FPG plus HbA1c is the largest and is significantly larger than that based on FPG (P = = 0.0008). For a cost-to-benefit ratio of 0.23888, the optimal critical line that has the highest utility is: 0.89 × HbA1c + 0.11 × FPG = 17.92. Those IFG participants whose FPG and HbA1c were above or on the line were referred to take an oral glucose tolerance test (OGTT) to diagnose diabetes. The optimal critical line is lower if a successive diabetes screening will be conducted 4 years after the previous screening. CONCLUSIONS. FPG &#8805; 126 and 2hPG &#8805; 200, as suggested by the ADA, are used in-dependently to define diabetes. The FPG level is easy to obtain, and using FPG alone is suggested for diabetes screening. It is difficult to get physicians and patients to perform an OGTT to get a 2hPG level because of the many drawbacks of the OGTT, especially in those patients who already have FPG < 126. It is also impractical to conduct an OGTT for everyone in a diabetes screening. Our data show that 37% of all subjects with new diabetes in the SHS baseline exam and 55.2% of those in the second exam have 2hPG &#8805; 200 but FPG < 126. These cases of diabetes cannot be detected if FPG is used alone in a diabetes screening. Therefore, although the small portion of diabetes in the NFG group (4.7% in the base-line and 6.9% in the second exam) may be ignored, those cases of diabetes among IFG participants (~20% in our data) need further consideration in a diabetes screening. It may be worthwhile for those IFG participants identified by the optimal critical line to take an OGTT. The optimal critical line and time interval between successive diabetes screenings need further study

Overcoming Recruitment Challenges: A Pilot Study in Arab Americans

While diabetes prevalence and cardiovascular risk factors have been increasing among Arab populations worldwide, few studies of Arab Americans have been conducted because of the difficulty in recruiting Arab American participants. Cultural sensitivity and social awareness of different immigrant groups could ensure successful recruitment and retention in clinical studies. While the primary objective of our overall research project was to determine the prevalence of metabolic syndrome in Arab Americans, the focus of this article is to describe the methodology used to overcome challenges in recruiting and enrolling Arab Americans for a community-based study. We used novel methods, including open houses, religious-based venues, and engagement of community leaders, to encourage participation in this clinical and epidemiological study. A community-based approach involving community leaders and educators was useful in recruiting and encouraging participation in this study. As a result, we were able to collect clinical and anthropometric data from 136 Arab American men and women living in the Washington, DC, area and obtain information regarding their chronic diseases, mental health, and acculturation into U.S. culture and lifestyle. Our sampling methodology may serve as a model of a successful recruitment and enrollment strategy, and may assist other researchers to ensure sufficient power in future studies. Engagement of minority participants in clinical studies will enable the creation of targeted clinical intervention and prevention programs for underrepresented and understudied populations