Samuel S. Gidding

Association of Obesity in Early Adulthood and Middle Age With Incipient Left Ventricular Dysfunction and Structural Remodeling : The CARDIA Study (Coronary Artery Risk Development in Young Adults)

OBJECTIVESnThe goal of this study was to investigate the relationship of body mass index (BMI) and its 25-year changexa0to left ventricular (LV) structure and function.nnnBACKGROUNDnLongstanding obesity may be associated with clinical cardiac dysfunction and heart failure. Whether obesity relates to cardiac dysfunction during young adulthood and middle age has not been investigated.nnnMETHODSnThe CARDIA (Coronary Artery Risk Development in Young Adult) study enrolled white and black adults ages 18 to 30 years in 1985 to 1986 (Year-0). At Year-25, cardiac function was assessed by conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography (STE). Twenty-five-year change in BMI (classified as low:xa0<27 kg/m(2) and high:xa0≥27 kg/m(2)) was categorized into 4 groups (Low-Low, High-Low, Low-High, and High-High). Multiple linear regression was used to quantify the association between categorical changes in BMI (Low-Low as reference) with LV structural and functional parameters obtained in middle age, adjusting for baseline and 25-year change in risk factors.nnnRESULTSnThe mean BMI was 24.4 kg/m(2) in 3,265 participants included at Year-0. Change in BMI adjusted for risk factors was directly associated with incipient myocardial systolic dysfunction assessed by STE (High-High: β-coefficientxa0= 0.67; Low-High: β-coefficientxa0= 0.35 for longitudinal peak systolic strain) and diastolic dysfunction assessed by TDI (High-High: β-coefficientxa0=xa0-074; Low-High: β-coefficientxa0=xa0-0.45 for e) and STE (High-High: β-coefficientxa0=xa0-0.06 for circumferential early diastolic strain rate). Greater BMI was also significantly associated with increased LV mass/height (High-High: β-coefficientxa0= 26.11; Low-High: β-coefficientxa0= 11.87).nnnCONCLUSIONSnLongstanding obesity from young adulthood to middle age is associated with impaired LV systolic andxa0diastolic function assessed by conventional echocardiography, TDI, and STE in a large biracial cohort of adults agexa043xa0to 55xa0years.

Potential U.S. Population Impact of the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline

BACKGROUNDnThe 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults provides recommendations for the definition of hypertension, systolic and diastolic blood pressure (BP) thresholds for initiation of antihypertensive medication, and BP target goals.nnnOBJECTIVESnThis study sought to determine the prevalence of hypertension, implications of recommendations for antihypertensive medication, and prevalence of BP above the treatment goal among U.S. adults using criteria from the 2017 ACC/AHA guideline and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7).nnnMETHODSnThe authors analyzed data from the 2011 to 2014 National Health and Nutrition Examination Survey (Nxa0=xa09,623). BPxa0was measured 3 times following a standardized protocol and averaged. Results were weighted to produce U.S. population estimates.nnnRESULTSnAccording to the 2017 ACC/AHA and JNC7 guidelines, the crude prevalence of hypertension among U.S. adults was 45.6% (95% confidence interval [CI]: 43.6% to 47.6%) and 31.9% (95% CI: 30.1% to 33.7%), respectively, and antihypertensive medication was recommended for 36.2% (95% CI: 34.2% to 38.2%) and 34.3% (95% CI: 32.5% to 36.2%) of U.S. adults, respectively. Nonpharmacological intervention is advised for the 9.4% of U.S. adults with hypertension who are not recommended for antihypertensive medication according to the 2017 ACC/AHA guideline. Among U.S. adults taking antihypertensive medication, 53.4% (95% CI: 49.9% to 56.8%) and 39.0% (95% CI: 36.4% to 41.6%) had BP above the treatment goal according to the 2017 ACC/AHA and JNC7 guidelines, respectively.nnnCONCLUSIONSnCompared with the JNC7 guideline, the 2017 ACC/AHA guideline results in a substantial increase in thexa0prevalence of hypertension, a small increase in the percentage of U.S. adults recommended for antihypertensive medication, and more intensive BP lowering for many adults taking antihypertensive medication.

Changes in Circulating Satiety Hormones in Obese Children: A Randomized Controlled Physical Activity-Based Intervention Study

The aims of this study are to examine in children: (i) obesity‐related alterations in satiety factors such as leptin, ghrelin, and obestatin; (ii) the link between satiety factors and cardiometabolic risk factors; and (iii) the impact of a physical activity‐based lifestyle intervention on the levels of these satiety factors in the obese. We studied a total of 21 adolescents (BMI percentile, 99.0 ± 0.6 for 15 obese and 56.2 ± 1.1 for 6 lean). The obese subjects underwent a 3‐month randomized controlled physical activity‐based lifestyle intervention. Leptin, soluble leptin receptor (sOB‐R), ghrelin, and obestatin levels were determined as the primary outcome measures. Other markers of cardiometabolic disease such as inflammation and insulin resistance were also determined. Body composition was measured by dual‐energy X‐ray absorptiometry. The concentrations of ghrelin, obestatin, and sOB‐R were significantly lower in the obese children compared to the lean controls, whereas that of leptin was higher (all P < 0.05). Although intervention led to a net increase in obestatin (P < 0.01) and no change in ghrelin levels, the balance between ghrelin and obestatin (ratio of ghrelin to obestatin, G/O) decreased (P < 0.02). Intervention reduced leptin and increased sOB‐R (P < 0.01 for both). Significant associations between satiety factors and other cardiometabolic risk factors were also observed. Taken together, alterations in the levels of satiety factors are evident early in the clinical course of obesity, but physical activity‐based lifestyle intervention either prevented their continued increase or normalized their levels. These beneficial effects appear to aid in the maintenance of body weight and reduction in cardiovascular risk.

Treatment Gaps in Adults with Heterozygous Familial Hypercholesterolemia in the United States: Data from the CASCADE-FH Registry

Background— Cardiovascular disease burden and treatment patterns among patients with familial hypercholesterolemia (FH) in the United States remain poorly described. In 2013, the FH Foundation launched the Cascade Screening for Awareness and Detection (CASCADE) of FH Registry to address this knowledge gap. Methods and Results— We conducted a cross-sectional analysis of 1295 adults with heterozygous FH enrolled in the CASCADE-FH Registry from 11 US lipid clinics. Median age at initiation of lipid-lowering therapy was 39 years, and median age at FH diagnosis was 47 years. Prevalent coronary heart disease was reported in 36% of patients, and 61% exhibited 1 or more modifiable risk factors. Median untreated low-density lipoprotein cholesterol (LDL-C) was 239 mg/dL. At enrollment, median LDL-C was 141 mg/dL; 42% of patients were taking high-intensity statin therapy and 45% received >1 LDL-lowering medication. Among FH patients receiving LDL-lowering medication(s), 25% achieved an LDL-C <100 mg/dL and 41% achieved a ≥50% LDL-C reduction. Factors associated with prevalent coronary heart disease included diabetes mellitus (adjusted odds ratio 1.74; 95% confidence interval 1.08–2.82) and hypertension (2.48; 1.92–3.21). Factors associated with a ≥50% LDL-C reduction from untreated levels included high-intensity statin use (7.33; 1.86–28.86) and use of >1 LDL-lowering medication (1.80; 1.34–2.41). Conclusions— FH patients in the CASCADE-FH Registry are diagnosed late in life and often do not achieve adequate LDL-C lowering, despite a high prevalence of coronary heart disease and risk factors. These findings highlight the need for earlier diagnosis of FH and initiation of lipid-lowering therapy, more consistent use of guideline-recommended LDL-lowering therapy, and comprehensive management of traditional coronary heart disease risk factors.

Active and passive tobacco exposure

Both passive and active exposure to tobacco smoke have adverse cardiovascular consequences for children and adolescents. Smoking as a habit begins in mid-adolescence and is perpetuated by the highly addictive nature of nicotine. Smoking has been associated with decreased life expectancy from all causes and early atherogenesis. The physiologic effects of active, and possibly passive smoke exposure include endothelial injury, increased oxidizability of LDL cholesterol, lower HDL cholesterol, impaired exercise performance, and altered oxygen delivery. Physician roles have been limited to research into the harmful nature of tobacco in the past, but new roles in advocacy against tobacco companies and the treatment of nicotine addiction are evolving.

Associations between a parental history of premature cardiovascular disease and coronary artery calcium and carotid intima-media thickness: The Coronary Artery Risk Development in Young Adults (CARDIA) study

Background It is unclear if associations between a parental history of premature CVD (pCVD) and subclinical atherosclerosis are attenuated by adjustment for long-term risk factor levels through middle adulthood. Design Prospective community-based cohort study. Methods CARDIA participants who attended the year-20 exam (nu2009=u20092283, mean age 45 years) were grouped by pCVD status: maternal only, paternal only, any parental, and no parental history (referent). We used separate logistic regression models, adjusted for average risk factor levels over a 20-year follow up to assess associations of parental pCVD and subclinical atherosclerosis in offspring. Results White participants with any parental history of pCVD had a higher odds of coronary artery calcium (CAC) >0 than participants with no parental history (OR 1.55, 95% CI 1.01–2.37). This was largely driven by the association of a paternal history of pCVD with CAC >0 (OR 2.15, 95% CI 1.42–3.23), which was minimally attenuated by multivariable adjustment (OR 2.09, 95% CI 1.31–3.32). Similarly, adjusted associations between parental pCVD and intima-media thickness (IMT) >90% were observed in white participants with a paternal history of pCVD (OR 1.93, 95% CI 1.10–3.39) and any parental history pCVD (OR 1.67, 95% CI 1.02–2.74). No significant associations between a parental history of pCVD and the odds of subclinical atherosclerosis were observed in black participants. Conclusions Parental pCVD is independently associated with early development of subclinical atherosclerosis; these associations may be race-specific for participants in their fifth decade of life.

Cumulative blood pressure from early adulthood to middle age is associated with left atrial remodelling and subclinical dysfunction assessed by three-dimensional echocardiography: a prospective post hoc analysis from the coronary artery risk development in young adults study

Abstract Aims To evaluate the association of cumulative blood pressure (BP) from young adulthood to middle age with left atrial (LA) structure/function as assessed by three-dimensional echocardiography (3DE) in a large longitudinal bi-racial population study. Methods and results We conducted a prospective post hoc analysis of individuals enrolled at the Coronary Artery Risk Development in Young Adults, which is a multi-centre bi-racial cohort with 30u2009years of follow-up. Cumulative systolic and diastolic BP levels were defined by summing the product of average millimetres of mercury and the years between each two consecutive clinic visits over 30u2009years of follow-up. Multivariable linear regression analyses were used to assess the relationship between cumulative systolic and diastolic BP with 3DE LA structure and function, adjusting for demographics and traditional cardiovascular risk factors. A total of 1033 participants were included, mean age was 55.4u2009±u20093.5u2009years, 55.2% women, 43.9% blacks. Cumulative systolic BP had stronger correlations than cumulative diastolic BP. Higher cumulative systolic BP was independently associated with higher 3D LA volumes: maximum (βu2009=u20091.74, Pu2009=u20090.004), pre-atrial contraction (βu2009=u20091.87, Pu2009<u20090.001), minimum (βu2009=u20090.76, Pu2009=u20090.04), total emptying (βu2009=u20090.98, Pu2009=u20090.006), active emptying (βu2009=u20091.12, Pu2009<u20090.001), and lower magnitude 3D LA early diastolic strain rate (βu2009=u20090.05, Pu2009=u20090.02). Higher cumulative diastolic BP was independently associated with higher 3D LA active emptying volume (βu2009=u20090.66, Pu2009=u20090.002), lower magnitude 3D LA early diastolic strain rate (βu2009=u20090.05, Pu2009=u20090.004), and higher magnitude 3D LA late diastolic strain rate (βu2009=u2009−0.04, Pu2009=u20090.05). Conclusion Higher cumulative BP from early adulthood throughout middle age was associated with adverse LA remodelling evaluated by 3D echocardiography.

Left ventricular global function index predicts incident heart failure and cardiovascular disease in young adults: the coronary artery risk development in young adults (CARDIA) study

AIMSnLeft ventricular (LV) ejection fraction (LVEF) is an extensively utilized marker of LV function that is often interpreted without recourse to alterations in LV geometry and hypertrophy. LV global function index (LVGFI) is a novel marker that incorporates LV structure in the assessment of LV cardiac performance. We evaluated the prognostic utility of LVGFI from young adulthood into middle age for incident heart failure (HF) and cardiovascular disease (CVD) in comparison to LVEF.nnnMETHODS AND RESULTSnIncluded were 4107 CARDIA participants with echocardiograms in Year-5 (1990-1991). LVGFI was defined as LV stroke volume/LV global volume*100, where LV global volume was the sum of the LV mean cavity volume ((LV end-diastolic volume + LV end-systolic volume)/2) and myocardial volume (LV mass/density). Adjusted Cox proportional hazard models were utilized to predict incident HF and CVD outcomes. Mean age of participants was 29.8u2009±u20093.7u2009years, 55% female, and 48.7% black. Higher body mass index [beta coefficient (B)u2009=u2009-0.11 standard error (SE)u2009=u20090.02, Pu2009<u20090.001], higher blood pressure (Bu2009=u2009-0.04, SEu2009=u20090.01, Pu2009<u20090.01), smoking (Bu2009=u2009-0.82, SEu2009=u20090.22, Pu2009<u20090.001), male sex (Pu2009<u20090.001), and black race (Pu2009<u20090.001) were associated with worse LVGFI. A total of 207 incident CVD events were observed over the course of 98xa0035 person-years at risk. Higher LVGFI was associated with HF, hazard ratio (HR)u2009=u20090.70, 95% confidence interval (CI) (0.54-0.91), hard CVD HRu2009=u20090.83, 95% CI (0.71-0.96), and all CVD HRu2009=u20090.83, 95% CI (0.72-0.96). For HF outcomes, Harrells C-statistic for LVGFI (0.80) was greater than LVEF (0.66).nnnCONCLUSIONnLVGFI is a strong, independent predictor of incident HF and CVD that provides incremental prognostic value compared with LVEF. Male sex, black race, obesity, hypertension, and smoking are associated with worse LVGFI in the early adult lifespan.