Treating hypertension in the very elderly-benefits, risks, and future directions, a focus on the hypertension in the very elderly trial.

Although the number of individuals reaching 80 who are considered to be healthy is increasing, the very elderly are likely to have long-term conditions, to report symptoms and/or be taking at least one regular medication. The impact of antihypertensive treatment has to be taken into account in this context. The treatment regimen in Hypertension in the Very Elderly Trial with a goal blood pressure of <150/80 mmHg has been shown to provide benefits in terms of a reduction in risk of total mortality, stroke, and cardiovascular events with potential benefits and no evidence of increased risk for fracture, dementia, depression, and quality-of-life outcomes. Questions remain as to the level of benefit that would be accrued in the frailer elderly and those at extreme age, for example, over 90.

Influenza vaccination and major adverse vascular events in high-risk patients.

BACKGROUND: We sought to determine the association between influenza vaccination and major adverse vascular events because the association remains uncertain. METHODS AND RESULTS: A total of 31 546 participants were enrolled from 40 countries. Eligibility included age ≥55 years and known vascular disease. The primary outcome was a composite of death resulting from cardiovascular causes, myocardial infarction, or stroke during 4 influenza seasons (2003-2007). Influenza vaccination was associated with a lower risk of the outcome during 3 influenza seasons (defined using World Health Organization FluNet reports): 2004 to 2005 (adjusted odds ratio [OR], 0.62; 95% confidence interval [CI], 0.50-0.77), 2005 to 2006 (adjusted OR, 0.69; 95% CI, 0.53-0.91), and 2006 to 2007 (adjusted OR, 0.52; 95% CI, 0.42-0.65), the same years that circulating influenza matched the vaccine antigen. In 2003 to 2004, there was an incomplete match between circulating influenza and the vaccine antigen, and there was no association between influenza vaccination and the outcome (adjusted OR, 0.96; 95% CI, 0.73-1.27). However, tests of potential biases in the analyses revealed associations between influenza vaccination and outcome during noninfluenza seasons except 2003 to 2004. The summary ORs in the influenza season (OR, 0.65; 95% CI, 0.58-0.74]) and noninfluenza season (OR, 0.66; 95% CI, 0.57-0.76) were almost identical. The reduction in risk of noncardiovascular death associated with the influenza vaccine ranged from 73% to 79%. CONCLUSION: Although initial analyses suggest that influenza vaccination was associated with reduced risk of major adverse vascular events during influenza seasons when the influenza vaccine matched the circulating virus, sensitivity analyses revealed that risk of bias remained. A randomized trial is needed to definitively address this question.

Kidney function in the very elderly with hypertension: data from the hypertension in the very elderly (HYVET) trial.

BACKGROUND: numerous reports have linked impaired kidney function to a higher risk of cardiovascular events and mortality. There are relatively few data relating to kidney function in the very elderly. METHODS: the Hypertension in the Very Elderly Trial (HYVET) was a randomised placebo-controlled trial of indapamide slow release 1.5mg ± perindopril 2-4 mg in those aged ≥80 years with sitting systolic blood pressures of ≥160 mmHg and diastolic pressures of <110 mmHg. Kidney function was a secondary outcome. RESULTS: HYVET recruited 3,845 participants. The mean baseline estimated glomerular filtration rate (eGFR) was 61.7 ml/min/1.73 m(2). When categories of the eGFR were examined, there was a possible U-shaped relationship between eGFR, total mortality, cardiovascular mortality and events. The nadir of the U was the eGFR category ≥60 and <75 ml/min/1.73 m(2). Using this as a comparator, the U shape was clearest for cardiovascular mortality with the eGFR <45 ml/min/1.73 m(2) and ≥75 ml/min/1.73 m(2) showing hazard ratios of 1.88 (95% CI: 1.2-2.96) and 1.36 (0.94-1.98) by comparison. Proteinuria at baseline was also associated with an increased risk of later heart failure events and mortality. CONCLUSIONS: although these results should be interpreted with caution, it may be that in very elderly individuals with hypertension both low and high eGFR indicate increased risk.

Alcohol consumption and the risk of incident atrial fibrillation among people with cardiovascular disease.

BACKGROUND: Moderate alcohol consumption may reduce cardiovascular events, but little is known about its effect on atrial fibrillation in people at high risk of such events. We examined the association between moderate alcohol consumption and the risk of incident atrial fibrillation among older adults with existing cardiovascular disease or diabetes. METHODS: We analyzed data for 30 433 adults who participated in 2 large antihypertensive drug treatment trials and who had no atrial fibrillation at baseline. The patients were 55 years or older and had a history of cardiovascular disease or diabetes with end-organ damage. We classified levels of alcohol consumption according to median cut-off values for low, moderate and high intake based on guidelines used in various countries, and we defined binge drinking as more than 5 drinks a day. The primary outcome measure was incident atrial fibrillation. RESULTS: A total of 2093 patients had incident atrial fibrillation. The age- and sex-standardized incidence rate per 1000 person-years was 14.5 among those with a low level of alcohol consumption, 17.3 among those with a moderate level and 20.8 among those with a high level. Compared with participants who had a low level of consumption, those with higher levels had an increased risk of incident atrial fibrillation (adjusted hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.04-1.26, for moderate consumption; 1.32, 95% CI 0.97-1.80, for high consumption). Results were similar after we excluded binge drinkers. Among those with moderate alcohol consumption, binge drinkers had an increased risk of atrial fibrillation compared with non-binge drinkers (adjusted HR 1.29, 95% CI 1.02-1.62). INTERPRETATION: Moderate to high alcohol intake was associated with an increased incidence of atrial fibrillation among people aged 55 or older with cardiovascular disease or diabetes. Among moderate drinkers, the effect of binge drinking on the risk of atrial fibrillation was similar to that of habitual heavy drinking.

Muscular strength and diameter as determinants of aerobic power and aerobic power response to exercise training in CAD patients.

OBJECTIVE: Low exercise capacity and skeletal muscle strength are important predictors of all-cause mortality in healthy as well as diseased individuals. Compared to sedentary subjects, CAD patients have a decreased oxygen uptake (peakVO2) and show accompanying increased muscle fatiguability. Despite the known importance of oxygen extraction by peripheral muscles on improving peakVO2 and of the relationship between muscle strength and aerobic capacity, only few studies in CAD patients include measurements of muscle strength before and after cardiac rehabilitation. This study therefore aimed to evaluate how much of the variance in baseline peakVO2 and its response to exercise training can be explained by muscular parameters. METHODS: 260 CAD patients performed maximal incremental cycle ergometer testing and maximal knee muscle strength measurements. The rectus femoris diameter was measured using ultrasound. Zero order correlations were calculated and determinants of baseline and response in peakVO2 were analysed by multiple regression analysis. RESULTS: PeakVO2 and muscle strength and diameter increased significantly after three months of cardiac rehabilitation (P < 0.0001). Zero order correlations showed significant correlations between muscular parameters and baseline peakVO2 (P < 0.0001). 63% of the total variance in baseline peakVO2 could be explained by seven parameters with knee extensor muscular endurance as the strongest predictor (P < 0.0001). 32% of the variation in relative increase in peakVO2 could be explained by 5 determinants of which the increase in muscular endurance was the strongest determinant (P < 0.0001). CONCLUSIONS: Knee extensor muscular endurance and its response after training are the strongest muscular predictors in explaining peakVO2 and its response in CAD patients.

A genetic predisposition score for muscular endophenotypes predicts the increase in aerobic power after training: the CAREGENE study.

BACKGROUND: It is widely accepted that genetic variability might explain a large part of the observed heterogeneity in aerobic capacity and its response to training. Significant associations between polymorphisms of different genes with muscular strength, anaerobic phenotypes and body composition have been reported. Muscular endophenotypes are positively correlated with aerobic capacity, therefore, we tested the association of polymorphisms in twelve muscular related genes on aerobic capacity and its response to endurance training. METHODS: 935 Coronary artery disease patients (CAD) who performed an incremental exercise test until exhaustion at baseline and after three months of training were included. Polymorphisms of the genes were detected using the invader assay. Genotype-phenotype association analyses were performed using ANCOVA. Different models for a genetic predisposition score (GPS) were constructed based on literature and own data and were related to baseline and response VO(2) scores. RESULTS: Carriers of the minor allele in the R23K polymorphism of the glucocorticoid receptor gene (GR) and the ciliary neurotrophic factor gene (CNTF) had a significantly higher increase in peakVO(2) after training (p < 0.05). Carriers of the minor allele (C34T) in the adenosine monophosphate deaminase (AMPD1) gene had a significantly lower relative increase (p < 0.05) in peakVO(2). GPS of data driven models were significantly associated with the increase in peakVO(2) after training. CONCLUSIONS: In CAD patients, suggestive associations were found in the GR, CNTF and the AMPD1 gene with an improved change in aerobic capacity after three months of training. Additionally data driven models with a genetic predisposition score (GPS) showed a significant predictive value for the increase in peakVO(2).

Heritability of left ventricular structure and function in Caucasian families.

AIMS: The aim of this study was to investigate the heritability as well as genetic and environmental correlations of left ventricular (LV) structural and functional traits in complex pedigrees of a Caucasian population. METHODS AND RESULTS: We randomly recruited 459 white European subjects from 52 families (50% women; mean age 45 years). LV structure was measured by M-mode and 2D echocardiography and LV function was measured by conventional Doppler and tissue Doppler imaging (TDI). Other measurements included blood pressure, anthropometric, and biochemical measurements. We estimated the heritability of LV traits while adjusting for covariables, including sex, age, body height and weight, systolic and diastolic blood pressures, and heart rate. With full adjustment, heritability of LV mass was 0.23 (P= 0.025). The TDI-derived mitral annular velocities Ea and Aa showed moderate heritability (h(2)= 0.36 and 0.53, respectively), whereas the mitral inflow A peak had weak heritability (h(2) = 0.25) and the E peak was not heritable (h(2) = 0.11). We partitioned the total phenotypic correlation when it reached significance, into a genetic and an environmental component. The genetic correlations were 0.61 between the E and Ea peaks and 0.90 between the A and Aa peaks. CONCLUSION: Our study demonstrated moderate heritability for LV mass as well as the mitral annular Ea and Aa peaks. We also found significant genetic correlations between the E and Ea peaks and between the A and Aa peaks. Our current findings support the ongoing research to map and detect genetic variants that contribute to the variation in LV mass and other LV structural and functional phenotypes.

Recommendations for interpretation of 12-lead electrocardiogram in the athlete.

Cardiovascular remodelling in the conditioned athlete is frequently associated with physiological ECG changes. Abnormalities, however, may be detected which represent expression of an underlying heart disease that puts the athlete at risk of arrhythmic cardiac arrest during sports. It is mandatory that ECG changes resulting from intensive physical training are distinguished from abnormalities which reflect a potential cardiac pathology. The present article represents the consensus statement of an international panel of cardiologists and sports medical physicians with expertise in the fields of electrocardiography, imaging, inherited cardiovascular disease, cardiovascular pathology, and management of young competitive athletes. The document provides cardiologists and sports medical physicians with a modern approach to correct interpretation of 12-lead ECG in the athlete and emerging understanding of incomplete penetrance of inherited cardiovascular disease. When the ECG of an athlete is examined, the main objective is to distinguish between physiological patterns that should cause no alarm and those that require action and/or additional testing to exclude (or confirm) the suspicion of an underlying cardiovascular condition carrying the risk of sudden death during sports. The aim of the present position paper is to provide a framework for this distinction. For every ECG abnormality, the document focuses on the ensuing clinical work-up required for differential diagnosis and clinical assessment. When appropriate the referral options for risk stratification and cardiovascular management of the athlete are briefly addressed.

The CAREGENE study: genetic variants of the endothelium and aerobic power in patients with coronary artery disease.

OBJECTIVES: Aerobic phenotypes show a wide variability to similar aerobic training stimuli, which can be partly attributed to heritability. Endothelial function affects aerobic power. Various physiological pathways may influence the endothelial function. Therefore, we aimed to examine whether polymorphisms of the eNos gene, the CAT gene, the VEGF gene, the GPX1 gene, the subunit P22 phox of the NAD(P)H-odixase gene, the PPAR-alpha gene, and the PGC-alpha gene are associated with aerobic power or with its response to physical training in patients with coronary artery disease (CAD). METHODS: 935 biologically unrelated Caucasian patients with CAD who had exercised until exhaustion during graded bicycle testing at baseline and after completion of 3 months of training were included in the CAREGENE study (Cardiac Rehabilitation and GENetics of exercise performance). Polymorphisms were detected using the invader assay and MassARRAY technology. Haplotype analysis was performed on the polymorphisms of the eNos gene, the VEGF gene and the NAD(P)H-oxidase gene. RESULTS: Physical training significantly increased aerobic power by 24.2 +/- 0.6% (P < 0.001). Associations of P < 0.05 were found between aerobic power and the eNOS 273C>T variant and the catalase -262C>T variant and aerobic power response. Haplotypes of the eNOS polymorhisms were predictive of aerobic power and its response to training (P < 0.05). After Bonferroni correction of multiple testing no significant differences remained. CONCLUSION: We believe that genetic factors are very important in the explanation of the great variability of aerobic power and its response. However, after Bonferroni-correction, differences in these polymorphisms remained no longer statistically significant.

Effects of telmisartan, ramipril, and their combination on left ventricular hypertrophy in individuals at high vascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers reduce left ventricular hypertrophy (LVH). The effect of these drugs on LVH in high-risk patients without heart failure is unknown. METHODS AND RESULTS: In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), patients at high vascular risk and tolerant of ACE inhibitors were randomly assigned to ramipril, telmisartan, or their combination (n=23 165). In the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND), patients intolerant of ACE inhibitors were randomized to telmisartan or placebo (n=5343). Prevalence of LVH at entry in TRANSCEND was 12.7%. It was reduced by telmisartan (10.5% and 9.9% after 2 and 5 years) compared with placebo (12.7% and 12.8% after 2 and 5 years) (overall odds ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.0017). New-onset LVH occurred less frequently with telmisartan compared with placebo (overall odds ratio, 0.63; 95% CI, 0.51 to 0.79; P=0.0001). LVH regression was similar in the 2 groups. In ONTARGET, prevalence of LVH at entry was 12.4%. At follow-up, it occurred slightly less frequently with telmisartan (odds ratio, 0.92; 95% CI, 0.83 to 1.01; P=0.07) and the combination (odds ratio, 0.93; 95% CI, 0.84 to 1.02; P=0.12) than with ramipril, but differences between the groups were not significant. New-onset LVH was associated with a higher risk of primary outcome during follow-up (hazard ratio, 1.77; 95% CI, 1.50 to 2.07). CONCLUSIONS: In patients at high vascular risk, telmisartan is more effective than placebo in reducing LVH. New-onset LVH is reduced by 37%. The effect of combination of the 2 drugs on LVH is similar to that of ramipril alone.

Smoking as an independent risk factor for myocardial infarction or stroke in type 2 diabetes: a report from the Swedish National Diabetes Register.

BACKGROUND: Few earlier studies have analysed smoking as a risk factor for myocardial infarction (MI) or stroke in type 2 diabetic patients. DESIGN AND METHODS: A longitudinal study involved 13 087 female and male patients with type 2 diabetes from the Swedish National Diabetes Register with no previous MI or stroke at baseline, aged 30-74 years, and with data available for all analysed variables, followed up for mean 5.7 years. RESULTS: Adjusted hazard ratios (HRs) for smoking and first-incident fatal/nonfatal MI, stroke and total mortality were 1.7 [95% confidence interval (CI): 1.4-2.0; P<0.001], 1.3 (95% CI: 1.1-1.6; P = 0.006) and 1.8 (95% CI: 1.5-2.2; P<0.001), respectively, by Cox regression analysis, adjusted for age, sex, diabetes duration, hypoglycaemic treatment, haemoglobin A1c, blood pressure, body mass index, microalbuminuria, antihypertensive and lipid-lowering drugs. Adjusted HR was higher for fatal MI, 2.1 (95% CI: 1.7-2.7; P<0.001), than for nonfatal MI, 1.4 (95% CI: 1.2-1.7; P<0.001). The highest HRs were observed in more frequently smoking (22%), middle-aged patients (age <60 years) for fatal/nonfatal MI, 2.3 (95% CI: 1.8-3.1; P<0.001) and for total mortality, 2.5 (95% CI: 1.6-3.8, P<0.001), whereas lower HRs were observed in older and less smoking patients. With predicted cessation of smoking in patients aged below 60 years, 24% (95% CI: 15-33%) of cases of fatal/nonfatal MI and 24% (11-37%) of cases of total mortality may have been prevented. CONCLUSION: The risk for MI and total mortality associated with smoking is high in type 2 diabetes, especially in more frequently smoking, middle-aged patients, and was higher for MI than for stroke, and also higher for fatal than for nonfatal events. Smoking cessation would strongly affect risk reduction.

Hypertension in the elderly: new and old evidence that treatment may benefit the old.

Hypertension is prevalent and remains an important risk factor in elderly and very elderly. Randomized controlled outcome trials have shown benefit of antihypertensive treatment in patients with systolic diastolic hypertension and in patients with isolated systolic hypertension, aged 60 years and over. More recently benefit has also been shown in octogenerians with hypertension. Overall there is no strong evidence that protection against major cardiovascular events afforded by different drug classes varies substantially with age. Finally, blood pressure lowering therapy also improves prognosis in hypertensive patients with type 2 diabetes.

Left ventricular strain and strain rate in a general population.

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

Effects of genetic variation in adducin on left ventricular diastolic function as assessed by tissue Doppler imaging in a Flemish population.

BACKGROUND: We investigated the possible association between left ventricular diastolic function and the ADD1 Gly460Trp and ADD3 IVS11 +386A>G polymorphisms alone and in combination. METHODS: In a family-based population study (473 subjects; 50.5% women; mean age 50.5 years), we measured early (Ea) and late (Aa) diastolic peak velocities of the mitral annulus by tissue Doppler imaging. In multivariate-adjusted analyses, we investigated phenotype-genotype associations, while accounting for confounders and family structure. RESULTS: Lateral Ea/Aa ratio was higher in ADD1 Trp allele carriers than in GlyGly homozygotes (1.51 vs. 1.40; P = 0.005) and was lower in ADD3 A allele carriers than in GG homozygotes (1.42 vs. 1.55; P = 0.005). The effects of ADD1 on the lateral Ea and Ea/Aa weakened with older age (P < 0.05). The best fitting model for lateral Ea and Ea/Aa included ADD1, ADD3, and the three-way interaction term of both genes with age. Below the age of 50 years, the lateral Ea/Aa ratio was higher in ADD1 Trp allele carriers than in GlyGly homozygotes (1.91 vs. 1.73; P = 0.006), particularly in the presence of ADD3 GG homozygosity (2.46 vs. 1.80; P = 0.0008). In older subjects, these phenotype-genotype associations were not significant (P > 0.20). Transmission of the ADD1 Trp allele to offspring was associated with higher lateral Ea (+0.91; P = 0.026) and Ea/Aa ratio (+0.23; P = 0.0008). CONCLUSION: Our population-based study demonstrated that left ventricular diastolic relaxation is modulated by genetic variation in ADD1 and ADD3. This association was more prominent in younger subjects in whom longstanding environmental factors and ageing are less likely to mask genetic effects.