Exercise blood pressure and the risk of incident cardiovascular disease (from the Framingham Heart Study)

Exaggerated systolic blood pressure (BP) augmentation with exercise has been associated with impaired endothelial function and cardiovascular risk. However, previous studies were largely restricted to men, did not evaluate diastolic BP, and focused on peak exercise measures, which are influenced by effort and fitness level. The aim of this study was to determine the association of exercise BP responses with risk of incident cardiovascular disease (CVD). BP was assessed during stage 2 of the Bruce protocol and during recovery in 3,045 Framingham Study subjects (mean age 43 years; 53% women). The association between exercise BP and CVD events during 20 years of follow-up was examined using Cox proportional hazards models. In age- and sex-adjusted analyses, exercise systolic and diastolic BP were associated with incident CVD (adjusted hazard ratios [HRs] for top quintile 1.55, 95% confidence interval [CI] 1.18 to 2.04; and 1.77, 95% CI 1.35 to 2.31, respectively, relative to the lower 4 quintiles; p <0.005). After adjustment for BP at rest and conventional risk factors, exercise diastolic BP (HR 1.41, 95% CI 1.01 to 1.95, p = 0.04), but not exercise systolic BP (HR 0.97, 95% CI 0.68 to 1.38, p = 0.86), remained a significant predictor of CVD. Similarly, in recovery responses after exercise, only diastolic BP (HR 1.53, 95% CI 1.08 to 2.18, p = 0.02) predicted incident CVD in multivariable models. In conclusion, in middle-aged adults, diastolic BP during low-intensity exercise and recovery predicted incident CVD. Our findings support the concept that dynamic BP provides incremental information to BP at rest and suggest that exercise diastolic BP may be a better predictor than exercise systolic BP in this age group.     

Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of human bone marrow cells

Fibroblast growth factor-4 (FGF-4), a highly mitogenic protein encoded by the k-fgf/hst oncogene, stimulates the growth of a variety of cells of mesenchymal and neuroectodermal origin. Addition of FGF-4 to human long-term bone marrow cultures increased both the cell density of the stromal layer and the number of hematopoietic colony forming cells in the cultures in a dose-dependent manner. Hematopoiesis in the stromal layer persisted for up to 8 months. Erythropoiesis was maintained for up to 4 weeks, but granulocytes were the predominant nonadherent cell type. Cultures treated with FGF had increased numbers of monocytes compared with control cultures and some CD14+, CD45+ monocytes could still be detected after 8 months of continuous culture. The addition of the growth factor increased the rate of growth of the stromal layer and appeared to delay its senescence. Subcultures made in the presence of FGF-4 had up to 10-fold increases in plating efficiency and grew as relatively uniform monolayers. These subcultures retained the capacity to support hematopoiesis for several months, while untreated subcultures, made without FGF-4, grew erratically and generally lost the capacity to support hematopoiesis within 4 to 6 weeks. The improved growth after subculture greatly enhanced the reliability of limit- dilution assays of multipotential hematopoietic stem cells that use stromal cell monolayers. The primary effect of FGF-4 appeared to be on the stromal cells of the long-term bone marrow cultures, but a direct effect on hematopoietic progenitors could not be ruled out.     

Variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in the Framingham Heart Study

OBJECTIVE: To examine the association between variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in men and women. DESIGN: In 1780 unrelated members of the community-based Framingham Heart Study offspring cohort, systolic blood pressure and diastolic blood pressure were measured over a total of six examination cycles encompassing 24 years of follow-up. Multivariate regression analyses were used to assess the relation between untreated cross-sectional and longitudinal blood pressure and polymorphisms at the estrogen receptor-alpha (ESR1), estrogen receptor-beta (ESR2), aromatase (CYP19A1), and nuclear receptor coactivator 1 (NCOA1) genes after adjustment for common risk factors. RESULTS: In men, systolic blood pressure and pulse pressure (systolic blood pressure minus diastolic blood pressure) were associated with two polymorphisms in ESR1, while pulse pressure was also associated with variations in NCOA1 and CYP19A1. Polymorphisms in ESR1, CYP19A1, and NCOA1 were associated with diastolic blood pressure in women. CONCLUSIONS: Although the underlying relations between genes involved in estrogen action and hypertension remain to be completely understood, our findings provide suggestive evidence of gender-specific contributions of estrogen-related genes to blood pressure variation. As no correction for multiple testing was performed in the analyses, we view these results as suggestive and not definitive. Further studies are warranted to confirm these results using a comprehensive set of polymorphisms in order to shed more light on the involvement of estrogen in blood pressure regulation.     

Prevalence, correlates, awareness, treatment, and control of hypertension in a middle-aged urban population in Kerala

BACKGROUND: Hypertension is an important cause of cardiovascular morbidity and mortality. METHODS AND RESULTS: We conducted a cross-sectional survey of 314 middle-aged subjects (163 men; age range 40-60 years, mean 49 years) in urban Thiruvananthapuram City. Kerala, to estimate the prevalence of hypertension, examine its correlates, and assess the degree of awareness, treatment, and control of high blood pressure. Blood pressure was measured by a nurse graduate using a mercury column sphygmomanometer and a standardized technique. We used multivariable analyses to examine the sociodemographic and clinical correlates of hypertension. The overall prevalence of hypertension in our sample was 54.5% (men 56.3%, women 52.3%). The factors associated with an increased prevalence of hypertension were higher body-mass index (odds ratio for a value in the top tertile of 2.33, 95% confidence interval: 1.2-4.4), and older age (odds ratio for the age group 55-60 years of 2.65, 95% confidence interval: 1.3-5.6). An occupation involving moderate or greater physical activity was inversely associated with the prevalence of hypertension (odds ratio 0.35, 95% confidence interval 0.13-0.94). Among hypertensives, 39% were aware of the condition, while 29% were treated with blood pressure-lowering medications. Adequate control of elevated blood pressure was achieved in only 30.6% of treated hypertensives. In our community-based sample, over half of all middle-aged individuals were hypertensive, but less than a third were under treatment. Adequate control of hypertension was achieved in less than a third of the treated individuals. CONCLUSIONS: These observations re-emphasize the need for hypertension awareness programs targeting the general public and the increased use of opportunistic blood pressure screening, and underscore the importance of measures to increase the knowledge of current guidelines for the detection and treatment of hypertension among healthcare providers.     

Value and limitations of Doppler echocardiographic determination of mitral valve area in Lutembacher syndrome.

OBJECTIVES. Our objective was to compare the Doppler pressure half-time, Doppler continuity equation and two-dimensional echocardiographic planimetric methods of estimating mitral valve area in Lutembacher syndrome. BACKGROUND. Fluid dynamics theory predicts that mitral pressure half-time varies inversely with mitral valve area and directly with net chamber compliance and the peak early diastolic transmitral gradient in pure mitral stenosis. The effects of an atrial shunt on these interrelations have not been investigated. METHODS. Correlation and agreement between mitral valve area estimates obtained by the three methods and that obtained by cardiac catheterization was ascertained in 11 patients with Lutembacher syndrome. RESULTS. Valve areas determined by planimetry and the continuity equation method correlated and agreed well with catheterization measurements (r = 0.83 and 0.81, respectively). The pressure half-time method consistently overestimated mitral valve area; the extent of overestimation was greater in patients with larger atrial shunts. The hemodynamic pressure half-time was independent of the mitral valve area, chamber compliance and the peak transmitral gradient. It was dependent on the magnitude of the atrial shunt, although the correlation obtained was only fair (r = 0.61). CONCLUSIONS. These findings suggest that the Doppler pressure half-time method is an inaccurate measure of mitral valve area whenever an atrial shunt coexists with mitral stenosis. Planimetry and the Doppler continuity equation methods yield accurate estimates of mitral valve area in Lutembacher syndrome.     

How to diagnose heart failure with preserved ejection fraction: the HFA–PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the ‘HFA–PEFF diagnostic algorithm’. Step 1 (P=Pre‐test assessment) is typically performed in the ambulatory setting and includes assessment for heart failure symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non‐cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular (LV) ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e′), LV filling pressure estimated using E/e′, left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2–4 points) implies diagnostic uncertainty, in which case Step 3 (F₁: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F₂: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.