Karine R. Sahakyan

Normal-Weight Central Obesity: Implications for Total and Cardiovascular Mortality

Context It is uncertain whether measures of central obesity, such as waist-to-hip ratio (WHR), provide additional information beyond body mass index (BMI) in defining mortality risks associated with obesity. Contribution This population-based cohort study found that normal BMI and central obesity (defined by WHR) were associated with the worst long-term survival compared with individuals with normal fat distribution regardless of BMI category. Caution Information on body fat distribution was based on anthropometric indicators alone. Implication Normal weight with central obesity may represent an important group for targeted lifestyle modifications and other preventive strategies. Obesity defined by body mass index (BMI) or measures of central obesity, such as waist-to-hip ratio (WHR) and waist circumference, is associated with increased total and cardiovascular mortality (13). However, a recent meta-analysis (4) showed that being overweight according to BMI was actually associated with lower total mortality, challenging the paradigm that BMI is linked to increased mortality. Further, whether measures of fat distribution provide any incremental risk information beyond BMI alone has been a major source of controversy (2, 3, 58). Indeed, the 2013 American Heart Association/American College of Cardiology/The Obesity Society guideline for the management of obesity (9) does not recommend measuring WHR and assumes that persons with normal BMI are not exposed to any obesity-related cardiovascular risk in view of the limited available data proving otherwise. A recent large study (6) showed that incorporating waist circumference information in prediction models did not increase the prognostic value already provided by BMI; however, for a given BMI category, subgroups of waist circumference or WHR were also associated with increased mortality risk. Other studies showed that measures of central obesity, such as WHR, waist-to-height ratio (10, 11), or waist circumference alone, may provide additional information beyond BMI on mortality risk among middle-aged adults, provided there is no adjustment for obesity-related cardiovascular risk factors (2, 3, 7). Further, a study (12) has shown that measures of central obesity are more strongly associated with total and cardiovascular disease mortality rates than BMI. Another study (13) showed that persons with normal body weight measured by BMI, but who had increased body fat measured by bioimpedance, have higher total and cardiovascular mortality rates and a higher prevalence of metabolic syndrome and its components than those with normal BMI and body fat content. In addition, a recent meta-analysis of individual-patient data in those with coronary artery disease (12) has shown that persons with normal BMI who are in the top tertile of central obesity measures had the highest total mortality rate. These results have been attributed to several factors. First, the diagnostic accuracy of BMI for obesity is not optimal, especially in persons with greater body fat percentages and normal or intermediate BMI (14). Second, those with normal body weight and higher body fat have less muscle mass, which is a factor associated with higher mortality risk and metabolic dysregulation (15, 16). Third, animal and human studies (17) have recently shown that adipose tissue in the legs and buttocks may have a favorable effect on glucose metabolism. Finally, persons with a central distribution of fat, particularly when measured with WHR, have less adipose tissue in the lower extremities (17). To our knowledge, no studies in the general U.S. population have specifically focused on assessing the mortality risk in persons with normal BMI and central obesity compared with those who are overweight or obese according to BMI. Thus, we hypothesized that persons with normal BMI and central obesity would have greater mortality risk than those who have any other combination of BMI and central obesity. We investigated the total and cardiovascular mortality risks associated with different patterns of body adiposity in a large cohort of participants in NHANES III (Third National Health and Nutrition Examination Survey) (1988 to 1994). Because hip circumference was not measured in the most recent National Health and Nutrition Examination Surveys (conducted yearly from 1999 to 2010) and WHR data to define central obesity were crucial to our primary hypothesis, we have used data from NHANES III instead. Methods Study Design and Participants NHANES III is a cross-sectional survey that produces generalizable health estimates for the U.S. population using a stratified, multistage, probability sampling design. From a sample of 39695 persons, 33994 were interviewed and 30818 were examined at mobile examination centers. The examination consisted of extensive anthropometric, physiologic, and laboratory testing. Waist and hip circumferences were measured by a trained examiner with a measuring tape positioned at the high point of the iliac crest for the waist and at the greatest circumference of the buttocks. The design and methods for the survey are available elsewhere (18). In our study, 16124 adults aged 18 years or older had WHRs available. Because extremely thin persons and those with a history of nonskin cancer have a higher mortality risk, we further restricted our analysis to persons with a BMI greater than 18.5 kg/m2 and those without a history of nonskin cancer. The resulting sample was 15184 participants (7249 men and 7935 women). Total and Cardiovascular Mortality Assessment Identifier data were matched to the National Death Index to determine mortality status, with mortality follow-up from the date of the NHANES survey through 31 December 2006. A complete description of the methodology to link baseline NHANES III data to the National Death Index can be found elsewhere (19). International Classification of Diseases, Ninth Revision (ICD-9), codes from 1986 to 1998 and International Classification of Diseases, 10th Revision (ICD-10), codes from 1999 to 2000 were used to ascertain the underlying cause of death. Cardiovascular deaths were defined as those with ICD-9 codes 390 to 398, 402, and 404 to 429 and ICD-10 codes I00 to I09, I11, I13, and I20 to I51 (NHANES III codes 53 to 75). Statistical Analysis The overarching analytic goal was to estimate the influence of various magnitudes of central obesity and BMI on total mortality. To do this, we conducted weighted survival modeling that enabled the estimation of the relative risk for mortality, quantified by the hazard ratio (HR), and the expected survival for NHANES III participants. The NHANES III survey design and sampling weights were incorporated into the statistical analysis to calculate weighted means, SEs for continuous variables, and weighted percentages for categorical variables. To determine the total mortality associated with the different patterns of adiposity, we created multivariable Cox proportional hazards models and adjusted for potential confounders previously shown to be associated with obesity and mortality (4). These variables were age at examination, sex, education level, and smoking history. Although we considered adjusting for obesity-related cardiovascular risk factors in the models, we did not adjust our final estimates for these factors. Epidemiologic obesity research has shown that it might be inappropriate to control for factors in the causal pathway between obesity and death, such as diabetes, atherogenic dyslipidemia, and hypertension. In testing for differences in mortality risk for combinations of central obesity (defined by WHR) and BMI, we considered higher-order interactions of WHR with BMI and other covariates. The association pattern of WHR and BMI was found to be different for men versus women (that is, statistically significant higher-order interaction terms), so the final modeling was conducted using sex-stratified data to more clearly present the findings. The interaction terms allowed the potential quadratic risks (U-shaped risks) of values for these variables. The estimated model contains polynomial functions of BMI and WHR (for example, BMI2 and BMI2WHR2). These terms allow for relationships that are more sensitive to change in risk for mortality based on unique combinations (profiles) of WHR and BMI. The estimated risk function, when other covariates in the model are controlled for, will resemble a saddle with high- and low-risk areas. When possible, covariates were the grand mean centered to lessen the collinearity induced from quadratic effects. Likelihood ratio tests were used to determine whether these higher-order model terms could be removed. The proportional hazards assumption for all variables was assessed and satisfied for the final models. After these models were established, we estimated HRs with estimated model variables for different combinations of WHR and BMI stratified by sex. For these comparisons, we chose a BMI of 22 kg/m2 to represent persons with normal BMI, 27.5 kg/m2 to represent overweight persons, and 33 kg/m2 to represent obese persons. For WHR, we chose 0.89 and 1.00 for men and 0.80 and 0.92 for women as a measure of central obesity. Each of these sets of values were chosen either to reflect the approximate midpoint of standard clinical interpretationsto avoid issues with values at common thresholds (for example, BMI values at 30 kg/m2)or to be clinical targets we sought to better understand. Wald-based (or large sample-based) HR estimates and their SEs were assessed to provide significance tests among these representative patient profiles (20). Once the fitted Cox model was deemed satisfactory, we sought to estimate measures of absolute risk by means-adjusted 5- and 10-year survival estimates (21). In this analysis, we replicated observations to standardize (reweight) them and ensure balance across sex, age, WHR, and BMI categories. The expected survival was computed as a weighted estimate

Normal-weight central obesity

Context It is uncertain whether measures of central obesity, such as waist-to-hip ratio (WHR), provide additional information beyond body mass index (BMI) in defining mortality risks associated with obesity. Contribution This population-based cohort study found that normal BMI and central obesity (defined by WHR) were associated with the worst long-term survival compared with individuals with normal fat distribution regardless of BMI category. Caution Information on body fat distribution was based on anthropometric indicators alone. Implication Normal weight with central obesity may represent an important group for targeted lifestyle modifications and other preventive strategies. Obesity defined by body mass index (BMI) or measures of central obesity, such as waist-to-hip ratio (WHR) and waist circumference, is associated with increased total and cardiovascular mortality (13). However, a recent meta-analysis (4) showed that being overweight according to BMI was actually associated with lower total mortality, challenging the paradigm that BMI is linked to increased mortality. Further, whether measures of fat distribution provide any incremental risk information beyond BMI alone has been a major source of controversy (2, 3, 58). Indeed, the 2013 American Heart Association/American College of Cardiology/The Obesity Society guideline for the management of obesity (9) does not recommend measuring WHR and assumes that persons with normal BMI are not exposed to any obesity-related cardiovascular risk in view of the limited available data proving otherwise. A recent large study (6) showed that incorporating waist circumference information in prediction models did not increase the prognostic value already provided by BMI; however, for a given BMI category, subgroups of waist circumference or WHR were also associated with increased mortality risk. Other studies showed that measures of central obesity, such as WHR, waist-to-height ratio (10, 11), or waist circumference alone, may provide additional information beyond BMI on mortality risk among middle-aged adults, provided there is no adjustment for obesity-related cardiovascular risk factors (2, 3, 7). Further, a study (12) has shown that measures of central obesity are more strongly associated with total and cardiovascular disease mortality rates than BMI. Another study (13) showed that persons with normal body weight measured by BMI, but who had increased body fat measured by bioimpedance, have higher total and cardiovascular mortality rates and a higher prevalence of metabolic syndrome and its components than those with normal BMI and body fat content. In addition, a recent meta-analysis of individual-patient data in those with coronary artery disease (12) has shown that persons with normal BMI who are in the top tertile of central obesity measures had the highest total mortality rate. These results have been attributed to several factors. First, the diagnostic accuracy of BMI for obesity is not optimal, especially in persons with greater body fat percentages and normal or intermediate BMI (14). Second, those with normal body weight and higher body fat have less muscle mass, which is a factor associated with higher mortality risk and metabolic dysregulation (15, 16). Third, animal and human studies (17) have recently shown that adipose tissue in the legs and buttocks may have a favorable effect on glucose metabolism. Finally, persons with a central distribution of fat, particularly when measured with WHR, have less adipose tissue in the lower extremities (17). To our knowledge, no studies in the general U.S. population have specifically focused on assessing the mortality risk in persons with normal BMI and central obesity compared with those who are overweight or obese according to BMI. Thus, we hypothesized that persons with normal BMI and central obesity would have greater mortality risk than those who have any other combination of BMI and central obesity. We investigated the total and cardiovascular mortality risks associated with different patterns of body adiposity in a large cohort of participants in NHANES III (Third National Health and Nutrition Examination Survey) (1988 to 1994). Because hip circumference was not measured in the most recent National Health and Nutrition Examination Surveys (conducted yearly from 1999 to 2010) and WHR data to define central obesity were crucial to our primary hypothesis, we have used data from NHANES III instead. Methods Study Design and Participants NHANES III is a cross-sectional survey that produces generalizable health estimates for the U.S. population using a stratified, multistage, probability sampling design. From a sample of 39695 persons, 33994 were interviewed and 30818 were examined at mobile examination centers. The examination consisted of extensive anthropometric, physiologic, and laboratory testing. Waist and hip circumferences were measured by a trained examiner with a measuring tape positioned at the high point of the iliac crest for the waist and at the greatest circumference of the buttocks. The design and methods for the survey are available elsewhere (18). In our study, 16124 adults aged 18 years or older had WHRs available. Because extremely thin persons and those with a history of nonskin cancer have a higher mortality risk, we further restricted our analysis to persons with a BMI greater than 18.5 kg/m2 and those without a history of nonskin cancer. The resulting sample was 15184 participants (7249 men and 7935 women). Total and Cardiovascular Mortality Assessment Identifier data were matched to the National Death Index to determine mortality status, with mortality follow-up from the date of the NHANES survey through 31 December 2006. A complete description of the methodology to link baseline NHANES III data to the National Death Index can be found elsewhere (19). International Classification of Diseases, Ninth Revision (ICD-9), codes from 1986 to 1998 and International Classification of Diseases, 10th Revision (ICD-10), codes from 1999 to 2000 were used to ascertain the underlying cause of death. Cardiovascular deaths were defined as those with ICD-9 codes 390 to 398, 402, and 404 to 429 and ICD-10 codes I00 to I09, I11, I13, and I20 to I51 (NHANES III codes 53 to 75). Statistical Analysis The overarching analytic goal was to estimate the influence of various magnitudes of central obesity and BMI on total mortality. To do this, we conducted weighted survival modeling that enabled the estimation of the relative risk for mortality, quantified by the hazard ratio (HR), and the expected survival for NHANES III participants. The NHANES III survey design and sampling weights were incorporated into the statistical analysis to calculate weighted means, SEs for continuous variables, and weighted percentages for categorical variables. To determine the total mortality associated with the different patterns of adiposity, we created multivariable Cox proportional hazards models and adjusted for potential confounders previously shown to be associated with obesity and mortality (4). These variables were age at examination, sex, education level, and smoking history. Although we considered adjusting for obesity-related cardiovascular risk factors in the models, we did not adjust our final estimates for these factors. Epidemiologic obesity research has shown that it might be inappropriate to control for factors in the causal pathway between obesity and death, such as diabetes, atherogenic dyslipidemia, and hypertension. In testing for differences in mortality risk for combinations of central obesity (defined by WHR) and BMI, we considered higher-order interactions of WHR with BMI and other covariates. The association pattern of WHR and BMI was found to be different for men versus women (that is, statistically significant higher-order interaction terms), so the final modeling was conducted using sex-stratified data to more clearly present the findings. The interaction terms allowed the potential quadratic risks (U-shaped risks) of values for these variables. The estimated model contains polynomial functions of BMI and WHR (for example, BMI2 and BMI2WHR2). These terms allow for relationships that are more sensitive to change in risk for mortality based on unique combinations (profiles) of WHR and BMI. The estimated risk function, when other covariates in the model are controlled for, will resemble a saddle with high- and low-risk areas. When possible, covariates were the grand mean centered to lessen the collinearity induced from quadratic effects. Likelihood ratio tests were used to determine whether these higher-order model terms could be removed. The proportional hazards assumption for all variables was assessed and satisfied for the final models. After these models were established, we estimated HRs with estimated model variables for different combinations of WHR and BMI stratified by sex. For these comparisons, we chose a BMI of 22 kg/m2 to represent persons with normal BMI, 27.5 kg/m2 to represent overweight persons, and 33 kg/m2 to represent obese persons. For WHR, we chose 0.89 and 1.00 for men and 0.80 and 0.92 for women as a measure of central obesity. Each of these sets of values were chosen either to reflect the approximate midpoint of standard clinical interpretationsto avoid issues with values at common thresholds (for example, BMI values at 30 kg/m2)or to be clinical targets we sought to better understand. Wald-based (or large sample-based) HR estimates and their SEs were assessed to provide significance tests among these representative patient profiles (20). Once the fitted Cox model was deemed satisfactory, we sought to estimate measures of absolute risk by means-adjusted 5- and 10-year survival estimates (21). In this analysis, we replicated observations to standardize (reweight) them and ensure balance across sex, age, WHR, and BMI categories. The expected survival was computed as a weighted estimate

Normal weight obesity and mortality in United States subjects ≥60 years of age (from the third national health and nutrition examination survey)

Current body mass index (BMI) strata likely misrepresent the accuracy of true adiposity in older adults. Subjects with normal BMI with elevated body fat may metabolically have higher cardiovascular and overall mortality than previously suspected. We identified 4,489 subjects aged ≥60 years (BMI = 18.5 to 25 kg/m(2)) with anthropometric and bioelectrical impedance measurements from the National Health and Nutrition Examination Surveys III (1988 to 1994) and mortality data linked to the National Death Index. Normal weight obesity (NWO) was classified in 2 ways: creation of tertiles with highest percentage of body fat and body fat percent cutoffs (men >25% and women >35%). We compared overall and cardiovascular mortality rates, models adjusted for age, gender, smoking, race, diabetes, and BMI. The final sample included 1,528 subjects, mean age was 70 years, median (interquartile range) follow-up was 12.9 years (range 7.5 to 15.3) with 902 deaths (46.5% cardiovascular). Prevalence of NWO was 27.9% and 21.4% in men and 20.4% and 31.3% in women using tertiles and cutoffs, respectively. Subjects with NWO had higher rates of abnormal cardiovascular risk factors. Lean mass decreased, whereas leptin increased with increasing tertile. There were no gender-specific differences in overall mortality. Short-term mortality (<140 person-months) was higher in women, whereas long-term mortality (>140 person-months) was higher in men. We highlight the importance of considering body fat in gender-specific risk stratification in older adults with normal weight. In conclusion, NWO in older adults is associated with cardiometabolic dysregulation and is a risk for cardiovascular mortality independent of BMI and central fat distribution.

Diagnostic accuracy of body mass index to identify obesity in older adults: NHANES 1999–2004

Background:Body composition changes with aging lead to increased adiposity and decreased muscle mass, making the diagnosis of obesity challenging. Conventional anthropometry, including body mass index (BMI), while easy to use clinically may misrepresent adiposity. We determined the diagnostic accuracy of BMI using dual-energy X-ray absorptiometry (DEXA) in assessing the degree of obesity in older adults.Methods:The National Health and Nutrition Examination Surveys 1999–2004 were used to identify adults aged ⩾60 years with DEXA measures. They were categorized (yes/no) as having elevated body fat by gender (men: ⩾25%; women ⩾35%) and by BMI ⩾25 and ⩾30 kg m−2. The diagnostic performance of BMI was assessed. Metabolic characteristics were compared in discordant cases of BMI/body fat. Weighting and analyses were performed per NHANES (National Health and Nutrition Examination Survey) guidelines.Results:We identified 4984 subjects (men: 2453; women: 2531). Mean BMI and % body fat was 28.0 kg m−2 and 30.8% in men, and 28.5 kg m−2 and 42.1% in women. A BMI ⩾30 kg m−2 had a low sensitivity and moderately high specificity (men: 32.9 and 80.8%, concordance index 0.66; women: 38.5 and 78.5%, concordance 0.69) correctly classifying 41.0 and 45.1% of obese subjects. A BMI ⩾25 kg m−2 had a moderately high sensitivity and specificity (men: 80.7 and 99.6%, concordance 0.81; women: 76.9 and 98.8%, concordance 0.84) correctly classifying 80.8 and 78.5% of obese subjects. In subjects with BMI <30 kg m−2, body fat was considered elevated in 67.1% and 61.5% of men and women, respectively. For a BMI ⩾30 kg m−2, sensitivity drops from 40.3% to 14.5% and 44.5% to 23.4%, whereas specificity remains elevated (>98%), in men and women, respectively, in those 60–69.9 years to subjects aged ⩾80 years. Correct classification of obesity using a cutoff of 30 kg m−2 drops from 48.1 to 23.9% and 49.0 to 19.6%, in men and women in these two age groups.Conclusions:Traditional measures poorly identify obesity in the elderly. In older adults, BMI may be a suboptimal marker for adiposity.

Differential effects of leptin on adiponectin expression with weight gain versus obesity

Background/Objective:Adiponectin exerts beneficial effects by reducing inflammation and improving lipid metabolism and insulin sensitivity. Although the adiponectin level is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans.Methods/Results:Forty-four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to either gain 5% of body weight by 8 weeks of overfeeding (n=34) or maintain weight (n=10). Modest weight gain of 3.8±1.2 kg resulted in increased adiponectin level (P=0.03), whereas weight maintenance resulted in no changes in adiponectin. Further, changes in adiponectin correlated positively with changes in leptin (P=0.0085). In-vitro experiments using differentiated human white preadipocytes showed that leptin increased adiponectin mRNA and protein expression, whereas a leptin antagonist had opposite effects. To understand the role of leptin in established obesity, we compared adipose tissue samples obtained from normal-weight versus obese subjects. We noted, first, that leptin activated cellular signaling pathways and increased adiponectin mRNA in the adipose tissue from normal-weight participants, but did not do so in the adipose tissue from obese participants. Second, we noted that obese subjects had increased caveolin-1 expression, which attenuates leptin-dependent increases in adiponectin.Conclusions:Modest weight gain in healthy individuals is associated with increases in adiponectin levels, which correlate positively with changes in leptin. In vitro, leptin induces adiponectin expression, which is attenuated by increased caveolin-1 expression. In addition, the adipose tissue from obese subjects shows increased caveolin-1 expression and impaired leptin signaling. This leptin signal impairment may prevent concordant increases in adiponectin levels in obese subjects despite their high levels of leptin. Therefore, impaired leptin signaling may contribute to low adiponectin expression in obesity and may provide a target for increasing adiponectin expression, hence improving insulin sensitivity and cardio-metabolic profile in obesity.

Normal weight obesity and functional outcomes in older adults

BACKGROUND Obesity defined by body mass index (BMI) is associated with higher levels of functional impairment. However, BMI strata misrepresent true adiposity, particularly in those with a normal BMI but elevated body fat (BF%) (normal weight obesity [NWO]) whom are at higher metabolic and mortality risk. Whether this subset of patients is associated with worsening functional outcomes is unclear. METHODS Subjects aged ≥60 years with a BMI ≥18.5 kg/m(2) from NHANES III (1988-1994) were included. We created sex-specific tertiles of BF%. Data on physical limitations (PL), instrumental (IADL) and basic activities of daily living (BADL) were obtained. The analysis focused on the association between NWO and these outcomes. Comparative rates among each tertile using logistic regression (referent=lowest tertile) were assessed, incrementally adding co-variates. RESULTS Of the 4484 subjects aged ≥60 years, 1528 had a normal BMI, and the range of the mean age of tertiles was 69.9-71.2 years. Lean mass was lowest in the elevated BF% group than in the middle or low tertiles (42.6 vs 44.9 vs 45.8; p<0.001). Those with NWO had higher PL risk than the referent in females only in our adjusted model (males OR 1.18 [0.63-2.21]; females OR 1.90 [1.04-3.48]) but not after incorporating lean mass (males OR 1.11[0.56-2.20]; females (1.73 [0.92-3.25]). Neither sex with high BF% had higher IADL risk than the corresponding tertiles (males OR 0.67 [0.35-1.33]; females OR 1.20 [0.74-1.93]). NWO was protective in males only (OR 0.28 [0.10-0.83]) but not in females (OR 0.64 [0.40-1.03]). CONCLUSIONS NWO is associated with increased physical impairment in older adults in females only, highlighting the importance of recognizing the association of obesity with disability in elders.

Leptin, Adiposity, and Mortality: Results From the National Health and Nutrition Examination Survey III, 1988 to 1994

OBJECTIVE To determine whether leptin is related to all-cause and cardiovascular (CV) mortality in older adults. PATIENTS AND METHODS Participants 60 years and older with plasma leptin level measurements from the National Health and Nutrition Examination Survey III (1988-1994) and mortality data linked to the National Death Index were included. We created sex-specific tertiles of leptin (men: 4.2-7.7 μg/L; women: 11.5-21.4 μg/L) to identify the effect of leptin on all-cause and CV mortality. We also determined whether leptin predicted mortality in patients with obesity. We classified obesity using 4 possible definitions: body mass index 30 kg/m(2) or greater; body fat 25% or more in men and 35% or more in women; waist circumference 102 cm or greater in men and 88 cm or greater in women; and waist-hip ratio 0.85 or higher in women and 0.95 or higher in men. Sex-specific proportional hazard models were used to assess the effect of leptin on all-cause and CV mortality. RESULTS Of 1794 participants, 51.6% were women; the mean age was 70.3±0.4 years, and the follow-up period was 12.5 years with 994 deaths (469 were CV deaths). All-cause mortality in the highest leptin tertile was significant neither in men (hazard ratio [HR], 1.23; 95% CI, 0.93-1.63) nor in women (HR, 0.97; 95% CI, 0.68-1.40). CV mortality was the highest in the highest leptin tertile in men (HR, 1.69; 95% CI, 1.06-2.70) but not in women (HR, 1.21; 95% CI, 0.73-1.98). Evaluating the effect of leptin in subgroups of different obesity definitions, we found that high leptin levels as predict CV mortality in men as measured by waist circumference or body fat. CONCLUSION Elevated leptin level is predictive of CV mortality only in men. Leptin may provide additional mortality discrimination in obese men.

EXPERIMENTAL SLEEP RESTRICTION INCREASES NOCTURNAL BLOOD PRESSURE AND ATTENUATES BLOOD PRESSURE DIPPING IN HEALTHY INDIVIDUALS

Although growing evidence suggests that insufficient sleep is linked to enhanced risk of adverse events including hypertension, mechanistic investigations supporting causal relationships are lacking. In this study we sought to evaluate changes in ambulatory blood pressure in healthy individuals

Ethnic differences in all-cause and cardiovascular mortality by physical activity levels among older adults in the US

ABSTRACT Aims: This study sought to determine whether the association between varying levels of physical activity (PA) and all-cause and cardiovascular mortality differ by race/ethnicity in older adults. Methods: The sample comprised 2520 women and 2398 men drawn from National Health and Nutrition Examination Survey III (1988–1994) aged ≥ 60 years. We used the metabolic equivalent (MET) of self-reported PA levels to define activity groups (inactive: those who did not report any PA; active: those who reported 3–6 METs for ≥5 times/week or >6 METs, ≥3 times/week; insufficiently active: those meeting neither criteria). Racial/Ethnic differences were modeled using proportional hazard regression (HR) adjusting for age, education, smoking, diabetes, and hypertension. Results: Among those classified as inactive, Non-Hispanic Blacks (NHB) (HR: 0.72, 95% CI: 0.58–0.90) and Mexican Americans (HR: 0.59, 95%CI: 0.45–0.78) had a lower risk of all-cause mortality when compared to non-Hispanic Whites (NHW). Among those classified as insufficiently active, Mexican Americans (HR: 0.63, 95% CI: 0.51–0.77), but not NHB (HR: 0.81, (95% CI: 0.64–1.02) had a lower risk of all-cause mortality when compared to NHWs Similar results were observed for cardiovascular mortality. Conclusion: Overall, PA in the elderly (either insufficient or active) is associated with a lower all-cause mortality across all race/ethnic groups as compared to NHW. Further investigation, including studies with larger sample, is needed to address the health consequences of varying degrees of PA in ethnically diverse populations.

Decreased exercise capacity and sleep-disordered breathing in patients with hypertrophic cardiomyopathy.

BACKGROUND Mechanisms of decreased exercise capacity in patients with hypertrophic cardiomyopathy (HCM) are not well understood. Sleep-disordered breathing (SDB) is a highly prevalent but treatable disorder in patients with HCM. The role of comorbid SDB in the attenuated exercise capacity in HCM has not been studied previously. METHODS Overnight oximetry, cardiopulmonary exercise testing, and echocardiographic studies were performed in consecutive patients with HCM seen at the Mayo Clinic. SDB was considered present if the oxygen desaturation index (number of ≥ 4% desaturations/h) was ≥ 10. Peak oxygen consumption (VO2 peak) (the most reproducible and prognostic measure of cardiovascular fitness) was then correlated with the presence and severity of SDB. RESULTS A total of 198 patients with HCM were studied (age, 53 ± 16 years; 122 men), of whom 32% met the criteria for the SDB diagnosis. Patients with SDB had decreased VO2 peak compared with those without SDB (16 mL O2/kg/min vs 21 mL O2/kg/min, P < .001). SDB remained significantly associated with VO2 peak after accounting for confounding clinical variables (P < .001) including age, sex, BMI, atrial fibrillation, and coronary artery disease. CONCLUSIONS In patients with HCM, the presence of SDB is associated with decreased VO2 peak. SDB may represent an important and potentially modifiable contributor to impaired exercise tolerance in this unique population.