Because the process of myocardial remodelling starts before the onset of symptoms, recent heart failure (HF) guidelines place special emphasis on the detection of subclinical left ventricular (LV) ...systolic and diastolic dysfunction and the timely identification of risk factors for HF. Our goal was to describe the prevalence and determinants (risk factors) of LV diastolic dysfunction in a general population and to compare the amino terminal probrain natriuretic peptide level across groups with and without diastolic dysfunction.
In a randomly recruited population sample (n=539; 50.5% women; mean age, 52.5 years), we measured early and late diastolic peak velocities of mitral inflow (E and A), pulmonary vein flow by pulsed-wave Doppler, and the mitral annular velocities (Ea and Aa) at 4 sites by tissue Doppler imaging. A healthy subsample of 239 subjects (mean age, 43.7 years) provided age-specific cutoff limits for normal E/A and E/Ea ratios and the differences in duration between the mitral A and the reverse pulmonary vein flows during atrial systole (DeltaAd-ARd). The number of subjects in diastolic dysfunction groups 1 (impaired relaxation), 2 (elevated LV end-diastolic filling pressure), and 3 (elevated E/Ea and abnormally low E/A) were 53 (9.8%), 76 (14.1%), and 18 (3.4%), respectively. We used Delta(Ad<ARd+10) to confirm possible elevation of LV filling pressures in group 2. Compared with subjects with normal diastolic function (n=392, 72.7%), group 1 (209 versus 251 pmol/L; P=0.015) and group 2 (209 versus 275 pmol/L; P=0.0003) but not group 3 (209 versus 224 pmol/L; P=0.65) had a significantly higher adjusted NT-probrain natriuretic peptide. Higher age, body mass index, heart rate, systolic blood pressure, serum insulin, and creatinine were significantly associated with a higher risk of LV diastolic dysfunction.
The overall prevalence of LV diastolic dysfunction in a random sample of a general population, as estimated from echocardiographic measurements, was as high as 27.3%.
Results of randomized controlled trials are consistent in showing reduced rates of stroke, heart failure and cardiovascular events in very old patients treated with antihypertensive drugs. However, ...inconsistencies exist with regard to the effect of these drugs on total mortality.
We performed a meta-analysis of available data on hypertensive patients 80 years and older by selecting total mortality as the main outcome. Secondary outcomes were coronary events, stroke, cardiovascular events, heart failure and cause-specific mortality. The common relative risk (RR) of active treatment versus placebo or no treatment was assessed using a random-effect model. Linear meta-regression was performed to explore the relationship between intensity of antihypertensive therapy and blood pressure (BP) reduction and the log-transformed value of total mortality odds ratios (ORs).
The overall RR for total mortality was 1.06 (95% confidence interval 0.89-1.25), with significant heterogeneity between hypertension in the very elderly trial (HYVET) and the other trials. This heterogeneity was not explained by differences in the follow-up duration between trials. The meta-regression suggested that a reduction in mortality was achieved in trials with the least BP reductions and the lowest intensity of therapy. Antihypertensive therapy significantly reduced (P < 0.001) the risk of stroke (35%), cardiovascular events (27%) and heart failure (50%). Cause-specific mortality was not different between treated and untreated patients.
Treating hypertension in very old patients reduces stroke and heart failure with no effect on total mortality. The most reasonable strategy is the one associated with significant mortality reduction; thiazides as first-line drugs with a maximum of two drugs.
Previous meta-analysis of outcome trials in hypertension have not specifically focused on isolated systolic hypertension or they have explained treatment benefit mainly in function of the achieved ...diastolic blood pressure reduction. We therefore undertook a quantitative overview of the trials to further evaluate the risks associated with systolic blood pressure in treated and untreated older patients with isolated systolic hypertension
Patients were 60 years old or more. Systolic blood pressure was 160 mm Hg or greater and diastolic blood pressure was less than 95 mm Hg. We used non-parametric methods and Cox regression to model the risks associated with blood pressure and to correct for regression dilution bias. We calculated pooled effects of treatment from stratified 2 X 2 contingency tables after application of Zelen's test of heterogeneity.
In eight trials 15 693 patients with isolated systolic hypertension were followed up for 3.8 years (median). After correction for regression dilution bias, sex, age, and diastolic blood pressure, the relative hazard rates associated with a 10 mm Hg higher initial systolic blood pressure were 1.26 (p=0.0001) for total mortality, 1.22 (p=0.02) for stroke, but only 1.07 (p=0.37) for coronary events. Independent of systolic blood pressure, diastolic blood pressure was inversely correlated with total mortality, highlighting the role of pulse pressure as risk factor.
Active treatment reduced total mortality by 13% (95% Cl 2–22, p=0.02), cardiovascular mortality by 18%, all cardiovascular complications by 26%, stroke by 30%, and coronary events by 23%. The number of patients to treat for 5 years to prevent one major cardiovascular event was lower in men (18
vs 38), at or above age 70 (19
vs 39), and in patients with previous cardiovascular complications (16
vs 37).
Drug treatment is justified in older patients with isolated systolic hypertension whose systolic blood pressure is 160 mm Hg or higher. Absolute benefit is larger in men, in patients aged 70 or more and in those with previous cardiovascular complications or wider pulse pressure. Treatment prevented stroke more effectively than coronary events. However, the absence of a relation between coronary events and systolic blood pressure in untreated patients suggests that the coronary protection may have been underestimated.
Aims Strain and strain rate (SR) are measures of deformation that reflect left ventricular (LV) function. To our knowledge, no previous study described these indexes in a general population. We ...therefore described peak-systolic strain and SR of the LV in the general population and derived diagnostic thresholds for these measurements in a healthy subgroup. Methods and results In 480 subjects enrolled in a family-based population study (50.5% women; mean age, 50.5 years; 37.2% hypertensive), we measured: (i) end-systolic longitudinal strain and peak-systolic SR from the basal portion of the LV inferior and inferolateral free walls; (ii) radial deformation of the LV inferolateral wall. Longitudinal (mean, 22.9%) and radial (59.2%) strain and longitudinal (1.31 s−1) and radial (3.40 s−1) SR decreased with age (P ≤ 0.007). Longitudinal and radial strain independently decreased (P ≤ 0.006) with relative wall thickness (RWT), longitudinal strain with the waist-to-hip ratio, and radial strain with body weight. In contrast, LV ejection fraction increased (P ≤ 0.0001) with age and RWT. Longitudinal and radial stain rate increased with heart rate (P ≤ 0.05). In healthy subgroup (n = 236), the fifth percentiles were 18.4 and 44.3%, and 0.99 and 2.43 s−1, for longitudinal and radial strain and SR, respectively. Conclusion We explored the early signs of LV systolic dysfunction in a general population, using tissue Doppler imaging technique. LV strain and SR decrease with age, body weight, central obesity, and RWT. Our current study resulted in the proposal for diagnostic thresholds for strain and SR, based on a healthy subgroup recruited via random sampling of the population.
Differentiation of cardiac fibroblasts (Fbs) into myofibroblasts (MyoFbs) is responsible for connective tissue build-up in myocardial remodelling. We examined MyoFb differentiation and reversibility.
...Adult rat cardiac Fbs were cultured on a plastic substratum providing mechanical stress, with conditions to obtain different levels of Fb differentiation. Fb spontaneously differentiated to proliferating MyoFb (p-MyoFb) with stress fibre formation decorated with alpha-smooth muscle actin (α-SMA). Transforming growth factor-β1 (TGF-β1) promoted differentiation into α-SMA-positive MyoFb showing near the absence of proliferation, i.e. non-p-MyoFb. SD-208, a TGF-β-receptor-I (TGF-β-RI) kinase blocker, inhibited p-MyoFb differentiation as shown by stress fibre absence, low α-SMA expression, and high proliferation levels. Fb seeded in collagen matrices induced no contraction, whereas p-MyoFb and non-p-MyoFb induced 2.5- and four-fold contraction. Fb produced little collagen but high levels of interleukin-10. Non-p-MyoFb had high collagen production and high monocyte chemoattractant protein-1 and tissue inhibitor of metalloproteinases-1 levels. Transcriptome analysis indicated differential activation of gene networks related to differentiation of MyoFb (e.g. paxilin and PAK) and reduced proliferation of non-p-MyoFb (e.g. cyclins and cell cycle regulation). Dedifferentiation of p-MyoFb with stress fibre de-polymerization, but not of non-p-MyoFb, was induced by SD-208 despite maintained stress. Stress fibre de-polymerization could also be induced by mechanical strain release in p-MyoFb and non-p-MyoFb (2-day cultures in unrestrained 3-D collagen matrices). Only p-MyoFb showed true dedifferentiation after long-term 3-D cultures.
Fb, p-MyoFb, and non-p-MyoFb have a distinct gene expression, ultrastructural, and functional profile. Both reduction in mechanical strain and TGF-β-RI kinase inhibition can reverse p-MyoFb differentiation but not non-p-MyoFb.
We assessed the prognostic value of ECG left ventricular hypertrophy (LVH) using Sokolow-Lyon (SL-LVH), Cornell voltage (CV-LVH) or Cornell product (CP-LVH) criteria in 3043 hypertensive people aged ...80 years and over enrolled in the Hypertension in the Very Elderly Trial.
Multivariate Cox proportional hazard models were used to estimate hazard ratios with 95% confidence intervals (CIs) for all-cause mortality, cardiovascular diseases, stroke and heart failure in participants with and without LVH at baseline. The mean follow-up was 2.1 years.
LVH identified by CV-LVH or CP-LVH criteria was associated with a 1.6-1.9-fold risk of cardiovascular disease and stroke. The presence of CP-LVH was associated with an increased risk of heart failure (hazard ratio 2.38, 95% CI 1.16-4.86). In sex-specific analyses, CV-LVH (hazard ratio 1.94, 95% CI 1.06-3.55) and CP-LVH (hazard ratio 2.36, 95% CI 1.25-4.45) were associated with an increased risk of stroke in women and of heart failure in men, CV-LVH (hazard ratio 6.47, 95% CI 1.41-29.79) and CP-LVH (10.63, 95% CI 3.58-31.57), respectively. There was no significant increase in the risk of any outcomes associated with Sokolow-Lyon-LVH. LVH identified by these three methods was not a significant predictor of all-cause mortality.
Use of Cornell voltage and Cornell product criteria for LVH predicted the risk of cardiovascular disease and stroke. Only Cornell product was associated with an increased risk of heart failure. This was particularly the case in men. The identification of ECG LVH proved to be important in very elderly hypertensive people.
Based on individual patient data, we performed a quantitative overview of trials in hypertension to investigate to what extent lowering of systolic blood pressure (SBP) and diastolic blood pressure ...(DBP) contributed to cardiovascular prevention. We selected trials that tested active antihypertensive drugs against placebo or no treatment. Our analyses included 12,903 young (30 to 49 years of age) patients randomized in 3 trials and 14,324 old (60 to 79 years of age) and 1209 very old (> or =80 years of age) patients enrolled in 8 trials. Antihypertensive treatment reduced SBP/DBP by 8.3/4.6 mm Hg in young patients, by 10.7/4.2 mm Hg in old patients, and by 9.4/3.2 mm Hg in very old patients, respectively, resulting in ratios of DBP to SBP lowering of 0.55, 0.39, and 0.32, respectively (P=0.004 for trend with age). In spite of the differential lowering of SBP and DBP, antihypertensive treatment reduced the risk of all cardiovascular events, stroke and myocardial infarction in the 3 age strata to a similar extent. Absolute benefit increased with age and with lower ratio of DBP to SBP lowering. Furthermore, in patients with a larger-than-median reduction in SBP, active treatment consistently reduced the risk of all outcomes irrespective of the decrease in DBP or the achieved DBP. These findings remained consistent if the achieved DBP averaged <70 mm Hg. In conclusion, our overview suggests that antihypertensive drug treatment improves outcome mainly through lowering of SBP.
Summary Background Cross-sectional studies suggest, by use of heart rate variability (HRV), that partial re-innervation of the sinus node may occur after heart transplantation (HTx). Our aim was to ...test this hypothesis by examining HRV in long-term longitudinal follow-up study of HTx recipients. Methods and results 14 HTx recipients (11 men) were studied 1–48 (median 13) months (baseline) and 119–172 (median 141) months after HTx (follow-up). At baseline and follow-up, electrocardiographic RR interval was continuously recorded in the supine position for 20 min. The signals were analyzed in the time domain and in the frequency domain by means of power spectral analysis. RR-interval decreased significantly from baseline to follow-up ( p < 0.05). This was associated with an increase of total power ( p < 0.001), absolute low frequency ( p < 0.001), and high frequency power ( p < 0.001), but unchanged relative low frequency and high frequency power. Conclusions The observed changes in HRV during long-term follow-up after HTx are compatible with partial re-innervation of the cardiac sinus node, as has been suggested by cross-sectional studies.
It is not well known which exercise intensity is needed to obtain blood pressure reductions in response to endurance training. We therefore compared the effect of training at lower and higher ...intensity on blood pressure, and, in addition on other cardiovascular risk factors, in at least 55-year-old sedentary men and women.
We used a randomized crossover design comprising three 10-week periods. In the first and third periods, participants exercised at, respectively, lower and higher intensity (33 and 66% of heart rate reserve) in random order, with a sedentary period in between. Training programmes were identical except for intensity and were performed three times, 1 h per week. Thirty-nine (18 men) out of 48 randomized participants completed the study; age averaged 59 years.
The change of aerobic power from baseline to the end of each period was more pronounced (P < 0.05) with higher intensity (+3.70 ml/kg min; P < 0.001) than with lower intensity training (+2.31 ml/kg min; P < 0.001). Systolic blood pressures at rest and during submaximal exercise were reduced with both intensities (P < 0.01), whereas diastolic office blood pressure was significantly reduced after higher intensity only (P < 0.01). There were no significant differences in blood pressure reduction between intensities. Ambulatory blood pressure remained unchanged after training. Only higher intensity training reduced weight (-1.09 kg; P < 0.001), body fat (-0.85%; P < 0.001), plasma triglycerides (-0.17 mmol/l; P < 0.05) and oxidized low-density lipoprotein (-5.92 U/l; P < 0.01).
Higher and lower intensity training reduces systolic office and exercise blood pressure to a similar extent, but does not alter ambulatory blood pressure; only higher intensity training favourably affects anthropometric characteristics and blood lipids.
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