Biomedical subjects
Philip R Liebson
Publications and source records attributed to Philip R Liebson.
Diabetes, gender, and left ventricular structure in African-Americans: the atherosclerosis risk in communities study.
BACKGROUND: Cardiovascular risk associated with diabetes may be partially attributed to left ventricular structural abnormalities. However, the relations between left ventricular structure and diabetes have not been extensively studied in African-Americans. METHODS: We studied 514 male and 965 female African-Americans 51 to 70 years old, in whom echocardiographic left ventricular mass measurements were collected for the ARIC Study. In these, we investigated the independent association of diabetes with left ventricular structural abnormalities. RESULTS: Diabetes, hypertension and obesity prevalences were 22%, 57% and 45%, respectively. Unindexed left ventricular mass was higher with diabetes in both men (238.3 +/- 79.4 g vs. 213.7 +/- 58.6 g; p < 0.001) and women (206.4 +/- 61.5 g vs. 176.9 +/- 50.1 g; p < 0.001), respectively. Prevalence of height-indexed left ventricular hypertrophy was higher in women while increased relative wall thickness was similar in men and women. Those with diabetes had higher prevalences of height-indexed left ventricular hypertrophy (52% vs. 32%; p < 0.001), and of increased relative wall thickness (73% vs. 64%; p = 0.002). Gender-adjusted associations of diabetes with left ventricular hypertrophy (OR = 2.29 95% CI:1.79-2.94) were attenuated after multiple adjustments in logistic regression (OR = 1.50 95% CI:1.12-2.00). Diabetes was associated with higher left ventricle diameter (OR = 2.13 95% CI:1.28-3.53) only in men and with higher wall thickness (OR = 1.89 95% CI:1.34-2.66) only in women. Attenuations in diabetes associations were frequently seen after adjustment for obesity indices. CONCLUSION: In African-Americans, diabetes is associated with left ventricular hypertrophy and, with different patterns of left ventricular structural abnormalities between genders. Attenuation seen in adjusted associations suggests that the higher frequency of structural abnormalities seen in diabetes may be due to factors other than hyperglycemia.
Muraglitazar and the FDA: what constitutes drug safety?
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Women's Health Initiative (WHI) Dietary Trial and Norwegian Vitamin Trial (NORVIT).
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ASCOT-Blood Pressure Trial (ASCOT-BPLA) and HOPE-TOO.
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Calcium channel blockers in the spectrum of antihypertensive agents.
Calcium channel blockers (CCBs) are widely used in the treatment of hypertension. Through blood pressure reduction, and possibly other mechanisms such as antioxidative effects, they may play a role in diminishing the risk for a variety of cardiovascular outcomes. The combination of CCBs with other newer antihypertensive agents such, as ACE inhibitors and angiotensin receptor blockers, may provide complementary effects on risk reduction in cardiovascular adverse events and renal disease. Although the efficacy of CCBs as antihypertensive agents has been adequately demonstrated, there have been concerns regarding the use of short acting dihydropyridines after acute myocardial infarction. There have also been questions about the role of CCBs with regards to other antihypertensive agents in renal disease. For example, differential effects of dihydropyridine and non-dihydropyridine CCBs may affect progression of renal disease and risk for diabetes. Certain precautions involving drug interactions are needed because of the effects of CCBs on the CYP450 enzyme systems.
Left ventricular mass indexed to height and prevalent MRI cerebrovascular disease in an African American cohort: the Atherosclerotic Risk in Communities study.
BACKGROUND AND PURPOSE: Previous studies have demonstrated that echocardiographic left ventricular mass (LVM) is an independent risk factor for stroke in whites. Despite the greater burden of stroke, the echocardiographic predictors of stroke in African Americans remain poorly understood. METHODS: This investigation is a retrospective analysis of prospectively collected data from the Jackson, Miss (all African American), cohort of the Atherosclerotic Risk in the Communities study. Between 1993 and 1995, 2445 participants received an echocardiogram, and a random subset (n=778) received cerebral MRI evaluating presence of infarcts or white matter disease (WMD; >3 on a scale of 0 to 9). Compared with the entire Jackson cohort, the random subset was older, had a lower body mass index (BMI), and a higher systolic blood pressure (SBP). Logistic regression models examined the relations of LVM indexed by height (LVM/height) to MRI findings adjusted for age, gender, BMI, SBP, hypertensive medications, diabetes, total/high-density lipoprotein cholesterol, smoking status, and history of myocardial infarction. RESULTS: The 667 participants (63% women; 62+/-4 years of age) had a high prevalence of hypertension (68%), obesity (46%), echocardiographic left ventricular hypertrophy (49%), MRI stroke (n=133), and WMD (n=92). Adjusted LVM/height was significantly associated with prevalent MRI stroke (odds ratio [OR], 1.3; 95% CI, 1.1 to 1.7; P=0.02) and WMD (OR, 1.5; 95% CI, 1.1 to 1.9; P=0.006; OR expressed per 1 SD LVM/height, 45 g/m). CONCLUSIONS: In this randomized subset of a population-based cohort of African American adults, LVM/height was related to MRI evidence of prevalent cerebrovascular disease. The current study supports the hypothesis that LVM/height is an important risk factor for stroke in multiple ethnicities.
Substudies of ALLHAT and Heart Protection Study.
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Women's health study (aspirin) and TNT.
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Comparison of the prognostic value of left ventricular hypertrophy in African-American men versus women.
Echocardiographically determined left ventricular (LV) hypertrophy may be a stronger risk factor of cardiovascular disease (CVD) for women than for men, although it is unclear whether reported gender differences are real or attributable to confounding. We evaluated echocardiographic LV hypertrophy (defined as LV mass/height(2.7) >/=51 g/m(2.7)) collected from the African-American population of the Atherosclerosis Risk in Communities Study. Incident CVD events (57 in men, 62 in women) were determined during a median follow-up of 4.9 years (interquartile range 4.3 to 5.6) and included nonfatal myocardial infarction, cardiac death, coronary revascularization, and stroke. We conducted 2 analyses. First, we created matched samples of 340 men and 812 women who had LV hypertrophy based on propensity score and estimated the gender-specific incidence rate ratios and population-attributable risks. Second, we evaluated the complete cohort (604 men and 1,113 women) with Poisson's regression after adjusting for age, body mass index, hypertension, diabetes mellitus, ratio of total cholesterol to high-density lipoprotein cholesterol, current smoking, and education level. LV hypertrophy was significantly predictive of incident CVD, and the association shown by analyses of matched propensity scores was similar in men and women (incidence rate ratio 1.88 vs 1.92, p = 0.97 for men, population-attributable risk 0.22 vs 0.26, p <0.07 for women). In the multivariate analysis, we found comparable effect estimates for LV hypertrophy (incidence rate ratio 1.66 vs 2.09, p = 0.55 for men; population-attributable risk 0.24 vs 0.32, p <0.07 for women). Thus, LV hypertrophy is a strong predictor of CVD in African-Americans, and the effect of LV hypertrophy on CVD is similar in men and women.
Optimal threshold value for left ventricular hypertrophy in blacks: the Atherosclerosis Risk in Communities study.
The distribution of echocardiographic left ventricular (LV) mass differs among ethnicities. Because ethnic-specific echocardiographic criteria for LV hypertrophy (LVH) are not established, we determined whether threshold values derived from overwhelmingly white populations are appropriate for blacks, a subgroup having more LVH. Between 1992 and 1994, LV mass was measured echocardiographically in the Jackson, Mississippi, black cohort of the Atherosclerosis Risk in Communities study. Participants free of prevalent cardiovascular disease (CVD) (n=1616; mean+/-SD, age 59+/-5.7; 65% women and 57% with hypertension) were included. The optimal LVH threshold value was selected from the continuum of LV mass index (LVMI=LV mass/height(2.7)) using 3 methods: (1) the best operating point from the area under the resulting receiver-operating characteristic (ROC) curve predicting incident CVD; (2) the value with the smallest probability value associated with incident CVD; and (3) visual inspection of functions of LVMI and CVD in the general additive model (GAM) plot. At a median follow-up of 6.8 years, there were 192 events (coronary heart disease=87, stroke=62, and congestive heart failure=43; incidence=17.6/1000 person-years). The best operating point from the resulting ROC analysis was 51.2 g/m(2.7) for sensitivity (53.4%) and specificity (61.5%). The Cox and GAM models adjusted for age, gender, systolic blood pressure, hypertension, diabetes, smoking, total cholesterol-to-high-density lipoprotein ratio, LVH by ECG criterion, and socioeconomic status found 50 to 51 g/m(2.7) as the optimal threshold for LVH in middle-aged blacks, corresponding to a minimum probability value and to a log-hazard ratio of zero, respectively. Because these values are close to the 51 g/m(2.7) established from predominantly white populations, this cutpoint is appropriate for both groups.
Role of surrogate markers in assessing patients with diabetes mellitus and the metabolic syndrome and in evaluating lipid-lowering therapy.
Diabetes mellitus and the metabolic syndrome (MS) are reaching epidemic proportions in the United States, and cardiovascular disease continues to be the leading cause of death among patients with diabetes. A range of noninvasive screening tools may help reduce the morbidity and mortality of patients with diabetes because of early detection of subclinical cardiovascular disease and active monitoring of the effectiveness of therapy. Surrogate markers of subclinical disease include conventional and contrast-enhanced ultrasound imaging of carotid artery intima-media thickness (c-IMT), 2-dimensional echocardiography, coronary artery calcium imaging, cardiac magnetic resonance imaging, ankle-brachial indices, and brachial artery reactivity testing. Because these noninvasive imaging tools are relatively comfortable and entail relatively low risk to the patient, they are ideal for initial screening and for the repeated imaging that is required for monitoring the effectiveness of therapy. Moreover, when used in large numbers of patients with diabetes, prediabetes, and the MS, these imaging tools may be useful in developing and validating thresholds for the use of lipid-lowering therapy as well as clear therapeutic goals for this population. In addition, contrast-enhanced c-IMT scans now produce real-time images of the vasa vasorum and neovascularization of atherosclerotic plaque, potentially causing a paradigm shift in our view of the genesis of atherosclerosis and affecting treatment options for all populations. Thus, surrogate markers may not only help improve individual patient outcomes, they also may help direct scarce medical resources to maximize medical benefits, improve overall medical care, and minimize costs and untoward side effects.
VALIANT and EUROPA.
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