Dharmendrakumar A. Patel

The contribution of childhood obesity to adult carotid intima-media thickness: the Bogalusa Heart Study

Objective:Although obese children are at increased risk for coronary heart disease in later life, it is not clear if the association results from the persistence of childhood obesity into adulthood. We examined the relation of both childhood and adult levels of body mass index (BMI, kg m−2) to carotid intima-media thickness (IMT) measured at the (mean) age of 36 years.Design and Subjects:Prior to the determination of adult IMT, the 1142 participants had been examined 7 (mean) times in the Bogalusa Heart Study.Measurements:In addition to BMI, levels of lipids, lipoproteins and blood pressure were measured at each examination. Cumulative levels of each risk factor were based on the areas under the individual growth curves calculated using multilevel models for repeated (BMI) measurements. We then examined the relation of these cumulative levels to adult IMT.Results:Carotid IMT was associated with cumulative levels of BMI in both childhood and adulthood (P<0.001 for each association). Furthermore, the association between childhood BMI and adult IMT persisted, but was reduced, after controlling for adult BMI. Although childhood levels of lipids, lipoproteins and blood pressure were also associated with adult IMT, these associations were not independent of adult levels of these risk factors.Conclusions:These results emphasize the adverse effects of elevated childhood BMI levels. In addition to the strong tracking of BMI levels from childhood to adulthood, there appears to be a modest, independent effect of childhood BMI on adult IMT. The prevention of childhood obesity should be emphasized.

Utility of Currently Recommended Pediatric Dyslipidemia Classifications in Predicting Dyslipidemia in Adulthood Evidence From the Childhood Determinants of Adult Health (CDAH) Study, Cardiovascular Risk in Young Finns Study, and Bogalusa Heart Study

Background— New age- and sex-specific lipoprotein cut points developed from National Health and Nutrition Examination Survey (NHANES) data are considered to be a more accurate classification of a high-risk lipoprotein level in adolescents compared with existing cut points established by the National Cholesterol Education Program (NCEP). The aim of this study was to determine which of the NHANES or NCEP adolescent lipoprotein classifications was most effective for predicting abnormal levels in adulthood. Methods and Results— Adolescent and adult measures of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were collected in 365 Australian, 1185 Finnish, and 273 US subjects participating in 3 population-based prospective cohort studies. Lipoprotein variables in adolescence were classified according to NCEP and NHANES cut points and compared for their ability to predict abnormal levels in adulthood. With the use of diagnostic performance statistics (sensitivity, specificity, positive predictive value, negative predictive value, area under receiver operating characteristic curve) in pooled and cohort-stratified data, the NHANES cut points (compared with NCEP cut points) were more strongly predictive of low high-density lipoprotein cholesterol in adults but less predictive of high total cholesterol, high low-density lipoprotein cholesterol, and high triglyceride levels in adults. We identified heterogeneity in the relative usefulness of each classification between cohorts. Conclusions— The separate use of NHANES cut points for high-density lipoprotein cholesterol and NCEP cut points for total cholesterol, low-density lipoprotein cholesterol, and triglycerides yielded the most accurate classification of adolescents who developed dyslipidemia in adulthood.

Clinical impact of left ventricular hypertrophy and implications for regression.

Left ventricular hypertrophy (LVH) is an independent risk factor and predictor of cardiovascular (CV) events and all-cause mortality. Patients with LVH are at increased risk for stroke, congestive heart failure, coronary heart disease, and sudden cardiac death. Left ventricular hypertrophy represents both a manifestation of the effects of hypertension and other CV risk factors over time as well as an intrinsic condition causing pathologic changes in the CV structure and function. We review the risk factors for LVH and its consequences, concentric remodeling, and its prognostic significance, clinical benefits and supporting evidence for LVH regression, and its implications for management. We conclude our review summarizing the various pharmacological and nonpharmacological therapeutic options approved for the treatment of hypertension and LVH regression and the supporting clinical trial data for these therapeutic strategies.

Body Composition and Coronary Heart Disease Mortality—An Obesity or a Lean Paradox?

OBJECTIVE To determine the combined effects of body mass index (BMI) and body fat (BF) on prognosis in coronary heart disease (CHD) to better understand the obesity paradox. PATIENTS AND METHODS We studied 581 patients with CHD between January 1, 2000, and July 31, 2005, who were divided into low (<25) and high BMI (≥25), as well as low (≤25% men and ≤35% women) and high BF (>25% in men and >35% in women). Four groups were analyzed by total mortality during the 3-year follow-up by National Death Index: low BF/low BMI (n=119), high BF/low BMI (n=26), low BF/high BMI (n=125), and high BF/high BMI (n=311). RESULTS During the 3-year follow-up, mortality was highest in the low BF/low BMI group (11%), which was significantly (P<.001) higher than that in the other 3 groups (3.9%, 3.2%, and 2.6%, respectively); using the high BF/high BMI group as a reference, the low BF/low BMI group had a 4.24-fold increase in mortality (confidence interval [CI], 1.76-10.23; P=.001). In multivariate logistic regression for mortality, when entered individually, both high BMI (odds ratio [OR], 0.79; CI, 0.69-0.90) and high BF (OR, 0.89; CI, 0.82-0.95) as continuous variables were independent predictors of better survival, whereas low BMI (OR, 3.60; CI, 1.37-9.47) and low BF (OR, 3.52; CI, 1.34-9.23) as categorical variables were independent predictors of higher mortality. CONCLUSION Although both low BF and low BMI are independent predictors of mortality in patients with CHD, only patients with combined low BF/low BMI appear to be at particularly high risk of mortality during follow-up. Studies are needed to determine optimal body composition in the secondary prevention of CHD.

Left atrial volume index predictive of mortality independent of left ventricular geometry in a large clinical cohort with preserved ejection fraction.

OBJECTIVE To determine the effect on mortality of the left atrial volume index (LAVI) and left ventricular (LV) geometry (normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy). PATIENTS AND METHODS From January 1, 2004, through December 31, 2006, we evaluated 36,561 patients with preserved ejection fraction with an average follow-up of 1.7±1.0 years. The LAVI was categorized as normal (≤28 mL/m(2)) or increased (mild, 29-33 mL/m(2); moderate, 34-39 mL/m(2); severe, ≥40 mL/m(2)). RESULTS Progressive increases in LAVI and mortality were noted with abnormal LV geometry. Similarly, abnormal LV geometry and mortality were significantly higher in patients with increased LAVI. In patients who died vs surviving patients, the LAVI ± SD was significantly higher (33.0±14.8 vs 28.1±10.8 mL/m(2); P<.001) and abnormal LV geometry was significantly more prevalent (62% vs 44%; P<.001). Compared with those with a normal LAVI, patients with a severe LAVI had a 42% increased risk of mortality. In patients with normal LV geometry or concentric remodeling, a severe LAVI was a significant independent predictor of mortality, with an increased risk of 28% and 46%, respectively. Similarly, in patients with eccentric hypertrophy and concentric hypertrophy, the mortality risk in patients with a severe LAVI was twice that of patients with a normal LAVI. Comparison of area under the curve (0.565 [without LAVI] vs 0.596 [with LAVI]; P<.001] and predictive models with and without LAVI for mortality prediction were significant, indicating increased mortality prediction by the addition of LAVI to other independent predictors. CONCLUSION The LAVI significantly predicts mortality risk, independent of LV geometry, and adds to the overall mortality prediction in a large cohort of patients with preserved systolic function.

Impact of echocardiographic left ventricular geometry on clinical prognosis

Abnormal left ventricular (LV) geometry, including LV hypertrophy (LVH), is associated with increased risk of major cardiovascular (CV) events and all-cause mortality and may be an independent predictor of morbid CV events. Patients with LVH have increased risk of congestive heart failure, coronary heart disease, sudden cardiac death and stroke. We review the risk factors for LVH and its consequences, as well as the risk imposed by concentric remodeling (CR). We also examine evidence supporting the benefits of LVH regression, as well as evidence regarding the risk of CR progressing to LVH, as opposed to normalization of CR. We also briefly review the association of abnormal LV geometry with left atrial enlargement and the combined effects of these structural cardiac abnormalities.

Body Composition and Mortality in a Large Cohort With Preserved Ejection Fraction: Untangling the Obesity Paradox

OBJECTIVE To evaluate the effects of body composition as a function of lean mass index (LMI) and body fat (BF) on the correlation between increasing body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and decreasing mortality, which is known as the obesity paradox. PATIENTS AND METHODS We retrospectively assessed 47,866 patients with preserved left ventricular ejection fraction (≥50%). We calculated BF by using the Jackson-Pollock equation and LMI using (1 - BF) × BMI. The population was divided according to the sex-adjusted BMI classification, sex-adjusted LMI classification, and sex-adjusted BF tertiles. The population was analyzed by using multivariate analysis for total mortality over a mean follow-up duration of 3.1 years by using the National Death Index, adjusting for left ventricular ejection fraction, left ventricular mass index, age, sex, and relative wall thickness. RESULTS In the entire population, higher BMI was narrowly associated (hazard ratio [HR], 0.99; P<.001) with lower mortality. The higher LMI group was clearly protective (HR, 0.71; P<.001), whereas BF tertile was associated with lower mortality only if no adjustment was made for LMI (HR, 0.87; P<.001 without LMI; HR, 0.97; P=.23 with LMI). In the lean patients, low BMI was clearly associated with higher mortality (HR, 0.92; P<.001) and lower BF tertile was associated with lower mortality only if no adjustment was made for LMI (HR, 0.80; P<.001 without LMI; HR, 1.01; P=.83 with LMI). The underweight patients stratified by BF seemed to have an increased mortality (HR, 1.91; 95% CI, 1.56-2.34) that was independent of LMI. However, in obese patients, both BMI (HR, 1.03; P<.001) and BF (HR, 1.18; P=.003) were associated with higher mortality, even after adjusting for LMI, which remained protective (HR, 0.57; P<.001) independently of BF. CONCLUSION Body composition could explain the inverse J shape of the mortality curve noted with increasing BMI. Body fat seems to be protective in this cohort only if no adjustment was made for LMI, although being underweight stratified by BF seems to be an independent risk factor. Lean mass index seems to remain protective in obese patients even when BMI is not.

Disparate effects of obesity and left ventricular geometry on mortality in 8088 elderly patients with preserved systolic function.

Abstract Background: Although left ventricular (LV) geometry has predicted cardiovascular (CV) prognosis, including in elderly cohorts, the role of obesity on CV prognosis has been more controversial. Objective: To assess the independent effects of obesity and LV geometry on all-cause mortality in a large cohort of elderly patients with preserved LV systolic function. Patients and Methods: We retrospectively assessed 8088 elderly patients (> 70 years) with an LV ejection fraction (LVEF) ≥ 50% who were referred for echocardiography at a large primary, secondary, and tertiary health care system in New Orleans. We specifically assessed clinical and echocardiographic features to determine the impact of body mass index (BMI) and LV geometric patterns, including concentric remodeling (CR) and LV hypertrophy (LVH) on all-cause mortality during an average 3.1-year follow-up. Results: Although abnormal LV geometry (P < 0.01) and LVH (P < 0.001) progressively increased with more obesity, total mortality was strongly and inversely (P < 0.0001) related with BMI. However, in each BMI subgroup, mortality progressively increased with abnormal LV geometry from normal, CR, eccentric LVH, and concentric LVH (P < 0.001 for all trends). In a multivariate analysis, abnormal LV geometry, including increased relative wall thickness (Chi-square 16; P < 0.0001) and LV mass index (Chi-square 12; P < 0.0001), and lower BMI (Chi-square 33; P < 0.0001) were independent predictors of mortality. Conclusion: Although an obesity paradox exists, in that obesity is associated with abnormal LV geometry but lower mortality, our data demonstrate that LV geometric abnormalities are prevalent in elderly patients with preserved systolic function and are associated with progressive increases in mortality.

Obesity paradox and the heart: which indicator of obesity best describes this complex relationship?

Purpose of reviewDespite the detrimental effects of obesity on coronary heart disease (CHD) and heart failure, obesity is found to be paradoxically associated with improved survival in secondary care of CHD and heart failure. This ‘obesity paradox’ is an area of active research, and it might be the result of an inaccurate working definition of obesity, which is traditionally defined in terms of BMI. We reviewed the recent literature on the paradox and examined different anthropomorphic measurements and their association with prognosis in cardiovascular diseases. Recent findingsIn CHD, obesity is associated with improved prognosis when defined by high BMI and body fat, independent of fat-free mass (FFM). High waist circumference seems to be associated with worse prognosis in some studies, but is associated with protection and an obesity paradox in those with poor cardiorespiratory fitness (CRF). In patients with heart failure, BMI, body fat and waist circumference, and possibly FFM, have been associated with improved survival. Despite these findings, intentional weight loss remains protective. In both CHD and heart failure, CRF seems to significantly impact the relationship between adiposity and subsequent prognosis, and an obesity paradox is only present with low CRF. SummaryBody composition, including waist circumference, body fat and FFM have a role in clinical practice. Emphasis should be placed on improving CRF, regardless of weight status. Intentional weight loss, particularly while maintaining FFM, should be encouraged in obese individuals.

Does fitness completely explain the obesity paradox

Theresulthasbeen an adverse impact on many of the major CV andcoronary heart disease (CHD) risk factors includingincreasing levels of arterial pressure, increasing insulinresistance (thus leading to increased prevalence ofmetabolic syndrome and type 2 diabetes mellitus),increasing dyslipidemia (especially increasing triglycer-ides and reducing levels of the cardioprotective high-density lipoprotein cholesterol), and increasing inflam-mation (evidenced by increased C-reactive protein), andalthough sedentary lifestyle may increase the prevalenceof obesity, increases in weight may also beget physicalinactivity. Not surprisingly, obesity increases almost allmajor CV diseases including hypertension, CHD, heartfailure (HF), peripheral arterial disease, and atrial fibrilla-tion. Numerous studies and large meta-analyses have nowclearly demonstrated that overweight and obese patientswith established CV diseases paradoxically have a betterprognosis than do comparable subjects who are lean.Most of the evidence demonstrating this obesityparadox, including the article in this issue of the Ameri-can Heart Journal by Uretsky et al,