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This randomized, double-blind, parallel-group, multicenter study compared the efficacy of amlodipine and losartan in an older hypertensive population, focusing on therapeutic coverage in the case of missed doses. Following a 4-week, single-blind, placebo washout period, 211 patients were randomly assigned to receive either 5 mg of amlodipine once daily or 50 mg of losartan once daily. Doses were doubled after 6 weeks of treatment if the diastolic blood pressure exceeded 90 mm Hg. After the 12-week treatment period, patients received the placebo for 2 days (drug holiday) to simulate two missed doses of antihypertensive medication. Twenty-four-hour ambulatory blood pressure monitoring was conducted at the end of the placebo washout period (baseline), upon completion of the 12-week treatment period (steady state), and after the 2-day drug holiday. Amlodipine was more effective than losartan in reducing patients' 24-h ambulatory blood pressure at the steady-state sampling time. The increases in 24-h blood pressure during the drug holiday averaged 6±2/2±1 mm Hg (P

OBJECTIVESNighttime blood pressure (BP) has been shown to be superior to daytime BP in predicting hypertension related target organ damage and cardiac mortality. In our Georgia Cardiovascular Twin Study, we showed that apart from the genes that also influence daytime BP, specific genetic determinants explained 44% and 67% of the nighttime systolic BP (SBP) and diastolic BP (DBP) heritabilities, respectively. Here, we determined whether these results could be confirmed in a much larger twin cohort of young adults with 24-hour ambulatory BP measurements.METHODSAmbulatory BP was available in 703 white twins (308 pairs and 87 singletons, aged 18-34 years, 50% males) from the Prenatal Programming Twin Study. A bivariate quantitative genetic twin model was used to analyze daytime and nighttime BP. We conducted a meta-analysis to compare and integrate results from the 2 twin cohorts.RESULTSModel fitting showed no sex differences for any of the measures. Heritabilities were 0.60 and 0.51 for SBP and 0.54 and 0.46 for DBP at daytime and nighttime. The specific heritability due to novel genetic effects emerging during the nighttime was 0.21 for SBP and 0.26 for DBP, which comprised 41% and 57% of the total nighttime heritability for SBP and DBP, respectively. Meta-analysis confirmed absence of cohort differences with very similar combined results.CONCLUSIONSIn addition to genes that influence both daytime and nighttime BP, a large part of the heritability is explained by genes that specifically influence BP at night.

Abstract— Elevated systolic blood pressure (SBP) correlates to cognitive decline and incident dementia. The effects of heart rate (HR), visit to visit HR variation, and visit to visit SBP variation are less well established. Patients without preexisting cognitive dysfunction (N=24 593) were evaluated according to mean SBP, SBP visit to visit variation (coefficient of variation [standard deviation/mean×100%], CV), mean HR, and visit to visit HR variation (HR-CV) in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease. Cognitive function was assessed with mini mental state examination. Cognitive dysfunction (fall in mini mental state examination ≤24 points), important cognitive decline (drop of ≥5 points), and cognitive deterioration (drop of >1 point per year or decline to < 24 points) were assessed. SBP and HR were measured over 10.7±2.2 (mean±SD) visits. Mean SBP, mean HR, and SBP-CV were associated with cognitive decline, dysfunction, and deterioration (all P P =0.0030) and mean HR ( P =0.0008) remained predictors for cognitive dysfunction (odds ratios [95% confidence intervals], 1.32 [1.10–1.58] for 5th versus 1st quintile of SBP-CV and 1.40 [1.18–1.66] for 5th versus 1st quintile of mean HR). Similar effects were observed for cognitive decline and deterioration. SBP-CV and mean HR showed additive effects. In conclusion, SBP-CV and mean HR are independent predictors of cognitive decline and cognitive dysfunction in patients at high CV risk. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT 00153101.

White coat hypertension is considered to be a benign condition that does not require antihypertensive treatment. Ambulatory blood pressure (ABP) was measured in 284 participants in the Hypertension in the Very Elderly Trial (HYVET), a double-blind randomized trial of indapamide sustained release 1.5 mg±perindopril 2 to 4 mg versus matching placebo in hypertensive subjects (systolic blood pressure 160–199 mm Hg) aged >80 years. ABP recordings (Diasys Integra II) were obtained in 112 participants at baseline and 186 after an average follow-up of 13 months. At baseline, clinic blood pressure (CBP) exceeded the morning ABP by 32/10 mm Hg. Fifty percent of participants fulfilled the established criteria for white coat hypertension. The highest ABP readings were in the morning (average 140/80 mm Hg), the average night-time pressure was low at 124/72 mm Hg, and the average 24-hour blood pressure was 133/77 mm Hg. During follow-up, the systolic/diastolic blood pressure placebo-active differences averaged 6/5 mm Hg for morning ABP, 8/5 mm Hg for 24-hour ABP, and 13/5 mm Hg for CBP. The lowering of blood pressure over 24 hours supports the reduction in blood pressure with indapamide sustained release±perindopril as the explanation for the reduction in total mortality and cardiovascular events observed in the main HYVET study. Because we estimate that 50% had white coat hypertension in the main study, this condition may benefit from treatment in the very elderly.

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.

2012 focused update of the ESC Guidelines for the management of atrial fibrillation : an update of the 2010 ESC Guidelines for the management of atrial fibrillation: developed with the special contribution of the European Heart Rhythm Association

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.

BackgroundThe A1166C polymorphism is located within the microRNA-155 binding site of the human angiotensin II (Ang II) type-1 receptor (AGTR1) gene. The C allele interferes with the base-pairing complementariness between AGTR1 mRNA and microRNA-155 and thereby increases AGTR1 protein expression in vitro. We hypothesized that left ventricular (LV) mass is associated with the AGTR1 A1166C polymorphism.MethodsAmong 708 individuals (mean age, 49.4 years; 51.8% women) randomly recruited in a white European population, we measured LV structure by two-dimensional guided M-mode echocardiography, the AGTR1 A1166C polymorphism and the 24-h urinary aldosterone. We applied a mixed model to assess phenotype-genotype associations while adjusting for covariables and accounting for relatedness.ResultsThe AA (49.1%), AC (42.8%), and CC (8.1%) genotypes were in Hardy-Weinberg equilibrium. Using a recessive model, CC homozygotes compared to A-allele carriers showed significant increases (P < 0.021) in LV mass index (+5.78 ± 2.25 g/m(2)), mean wall thickness (MWT) (+0.48 ± 0.15 mm), interventricular septum (IVS) (+0.60 ± 0.18 mm) and posterior wall thickness (PWT) (+0.34 ± 0.15 mm), but lower 24-h urinary aldosterone excretion (geometric mean, 22.4 vs. 19.0 nmol; P = 0.050). Sensitivity analyses in 552 participants untreated for hypertension were confirmatory.ConclusionsLV mass index is associated with the AGTR1 A1166C polymorphism. Further research should clarify to what extent this association might be mediated via different expression of AGTR1 as modulated by microRNA-155American Journal of Hypertension 2012; doi:10.1038/ajh.2011.244. ispartof: American Journal of Hypertension vol:25 issue:4 pages:472-478 ispartof: location:United States status: published

Objectives We sought to determine whether the blood pressure (BP) levels at which cardiovascular (CV) protection is achieved differ between diabetic and nondiabetic patients from the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). Background Greater absolute benefits of BP reductions have been claimed for diabetic as compared with nondiabetic patients. Methods A total of 25,584 patients (9,603 diabetic), older than 55 years, at high CV risk were randomized to ramipril, telmisartan, or both and observed for 4.6 years. We pooled the treatment arms to examine the relationships between BP and the primary composite outcome (CV death, nonfatal myocardial infarction or stroke, or hospitalized heart failure) and its components. Results The primary outcome occurred in 1,938 (20.2%) diabetic patients and in 2,276 (14.2%) nondiabetic patients. Compared with nondiabetic patients, diabetic patients had a significantly higher risk for the primary endpoint (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.38 to 1.57) and CV death (HR: 1.56; 95% CI: 1.42 to 1.71); myocardial infarction (HR: 1.30 (95% CI: 1.17 to 1.46); stroke (HR: 1.39; 95% CI: 1.23 to 1.56); and congestive heart failure hospitalization (HR: 2.06; 95% CI: 1.82 to 2.32). The CV risk was significantly higher in diabetic than in nondiabetic patients regardless of the systolic BP changes during treatment. In both diabetic and nondiabetic patients, progressively greater systolic BP reductions were accompanied by reduced risk for the primary outcome only if baseline systolic BP levels ranged from 143 to 155 mm Hg; except for stroke, there was no benefit in fatal or nonfatal CV outcomes by reducing systolic BP below 130 mm Hg. Conclusions The relationship between BP and overall CV risk had a similar pattern in diabetic and nondiabetic patients over a wide range of baseline and in-treatment BP values although, for the same systolic BP, a higher risk is observed in diabetic patients. (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial [ONTARGET]; NCT00153101 )

We reviewed the effect of resistance training on blood pressure and other cardiovascular risk factors in adults. Randomized, controlled trials lasting ≥4 weeks investigating the effects of resistance training on blood pressure in healthy adults (age ≥18 years) and published in a peer-reviewed journal up to June 2010 were included. Random- and fixed-effects models were used for analyses, with data reported as weighted means and 95% confidence limits. We included 28 randomized, controlled trials, involving 33 study groups and 1012 participants. Overall, resistance training induced a significant blood pressure reduction in 28 normotensive or prehypertensive study groups [−3.9 (−6.4; −1.2)/−3.9 (−5.6; −2.2) mm Hg], whereas the reduction [−4.1 (−0.63; +1.4)/−1.5 (−3.4; +0.40) mm Hg] was not significant for the 5 hypertensive study groups. When study groups were divided according to the mode of training, isometric handgrip training in 3 groups resulted in a larger decrease in blood pressure [−13.5 (−16.5; −10.5)/−6.1(−8.3; −3.9) mm Hg] than dynamic resistance training in 30 groups [−2.8 (−4.3; −1.3)/−2.7 (−3.8; −1.7) mm Hg]. After dynamic resistance training, V o 2 peak increased by 10.6% ( P =0.01), whereas body fat and plasma triglycerides decreased by 0.6% ( P P

INTRODUCTION: : In a previous meta-analysis, we derived pooled estimates for the association of left ventricular mass (LVM) and hypertrophy (LVH), as diagnosed by electrocardiography or echocardiography, with the ACE D/I polymorphism. We updated this meta-analysis until May 2009 only considering echocardiographic phenotypes. METHODS: : We computed pooled estimates from a random-effects model. RESULTS: : Across 38 studies, both DD homozygotes (n = 2440) and DI heterozygotes ( n = 4310) had higher (p ≤ 0.002) LVM or LVM index than II homozygotes (n = 2229). Across 21 studies with available data, this was due to increased mean wall thickness (MWT) with no difference in left ventricular internal diameter (LVID). Standardised differences (DD versus II) were 0.39 (p < 0.001) for LVM, 0.34 (p = 0.009) for MWT, and 0.066 (p = 0.26) for LVID. Across 16 studies (4894 participants), the pooled odds ratios of LVH (versus II homozygotes) were 1.11 (p = 0.29) and 1.02 (p = 0.88) for the DD and DI genotypes, respectively. Sensitivity analyses were confirmatory. CONCLUSIONS: : Our meta-analysis supports the hypothesis that the enhanced ACE activity associated with the D allele is associated with higher LV mass. Smaller sample size might explain the lack of significant association with LVH. ispartof: Journal of the Renin-Angiotensin-Aldosterone System vol:12 issue:3 pages:243-253 ispartof: location:England status: published

Cardiac fibrosis occurs with normal aging and may have important pathological consequences. Accumulating evidence shows that biochemical assessment of fibrosis using collagen markers such as serum levels of the aminoterminal propeptide of types I and III collagen (PINP, PIIINP) and the carboxyterminal telopeptide of type I collagen (ICTP) represents a practical, validated and non-invasive method to assess myocardial collagen turnover. It is generally accepted that a sedentary lifestyle may be at least partly responsible for the age-related changes in the cardiovascular system. We aimed to investigate whether dynamic aerobic endurance training at lower or higher intensity (33% and 66% of heart rate reserve) may influence markers of collagen synthesis (PINP, PIIINP) and degradation (ICTP) in at least 55-year-old healthy sedentary men and women. A randomised crossover study comprising three 10-week periods was performed. In the first and third period, participants exercised at, respectively, lower or higher intensity in random order, with a sedentary period in between. Training programs were identical except for intensity and were performed three times 50 min/week. 39 (18 men) out of 48 randomised participants completed the study; age averaged 59 years. Serum concentrations of PINP, PIIINP and ICTP were determined at baseline and at the end of each 10-week period. Our results showed that 10 weeks of endurance training at lower or higher intensity did not significantly alter serum markers of collagen synthesis and degradation in healthy older men and women.

Objective: To investigate the effect of oral creatine supplementation in conjunction with an exercise programme on physical fitness in patients with coronary artery disease or chronic heart failure. Design: Single centre double-blind randomized placebo controlled trial. Setting: Cardiac rehabilitation centre. Subjects and intervention: 70 (4 women) cardiac patients (age 57.5 (8.4) years) were randomized to a placebo (n = 37) or creatine (n = 33) treatment for three months. Combined aerobic endurance and resistance training (three sessions/ week) was performed during supplementation. Main Measures: Aerobic power was determined during graded bicycle testing, knee extensor peak isometric and isokinetic strength, endurance and recovery were assessed by an isokinetic dynamometer, and health related quality of life was evaluated with the SF-36 and MacNew Heart Disease questionnaires. In addition, blood samples were taken after an overnight fast and 24 hour urinary collection was performed. Results: At baseline there were no significant differences between both groups. We observed main time effects for aerobic power, muscle performance, health related quality of life, high density lipoprotein cholesterol and triglycerides (pre vs post; P0.05). Further, no detrimental effect on renal or liver function was observed nor were there any reports of side effects. Conclusion: Oral creatine supplementation in combination with exercise training does not exert any additional effect on the improvement in physical performance, health related quality of life, lipid profile in patients with coronary artery disease or chronic heart failure than exercise training alone.

Smoking is a predictor of the transition from normoglycaemia to impaired fasting glucose and increases the risk of type 2 diabetes, independent from possible confounders. In patients with diabetes as in non-diabetics, smoking is a significant and independent risk factor for all-cause mortality and for mortality from cardiovascular disease and corononary heart disease, as well as for aggregates of fatal and non-fatal cardiovascular events. There is little doubt that smoking is a risk factor for coronary heart disease, but this risk appears to be stronger than the risk for stroke in diabetics. Pathophysiological mechanisms by which smoking causes glucose intolerance and worsens clinical outcomes in established diabetes include greater insulin resistance, impaired beta-cell function and insulin secretion, chronic low-grade inflammation, endothelial dysfunction, as well as interacting indirectly with other factors known to aggravate diabetes and lifestyle factors. Smoking cessation programs are of great importance for primary care specialists dealing with diabetes.

Four dipping categories have been described, based on the night-day blood pressure ratio from 24-h ambulatory blood pressure recordings: extreme dippers (night-day blood pressure ratioor = 0.8), dippers (0.8ratioor = 0.9), nondippers (0.9ratioor = 1.0) and reverse dippers (ratio1.0). The main purpose of this article is to discuss the prognostic significance of these four dipping categories in hypertension, mainly based on a large meta-analysis of individual patient data. In hypertensive patients without cardiovascular disease at baseline and with statistical adjustment for confounders and 24-h blood pressure, mortality was lower in extreme dippers than in dippers, whereas the incidence of cardiovascular events was higher in reverse dippers. The worst prognosis for reverse dippers was also observed in hypertensive patients with major cardiovascular disease at baseline. Higher incidences of cardiovascular events and mortality were also found in reverse dippers in comparison with dippers in a comprehensive meta-analysis of population-based studies but outcome was not significantly different between extreme dippers and dippers. Based on these findings, there appears to be little doubt that reverse dipping is associated with a worse prognosis. Some studies suggest that prognosis is similar in nondippers and extreme dippers in comparison with dippers, but other studies suggest a somewhat worse prognosis in nondippers, or a better or worse prognosis in extreme dippers.

Background The aim of this study was to determine whether inhibition of superoxide dismutase (SOD) with diethyldithiocarbamic acid (DETC) could affect the collagen production, the mRNA and protein expression of collagen types I and III, and fibronectin in control and angiotensin II (ANG II)-treated cardiac fibroblasts. Its effect was compared with the SOD mimetics tempol and EUK-8 and with polyethyleneglycol (PEG)-SOD. Methods Cardiac fibroblasts were cultured to confluence, incubated in serum-free Dulbecco's modified Eagle's medium for 24 h, preincubated with(out) the tested inhibitors for 1 h and further incubated with(out) ANG II (1 micromol/l) for 24 h. Results DETC dose-dependently inhibited the activity of CuZn-SOD in cardiac fibroblasts. Superoxide anion production was increased by DETC and decreased by tempol in control and ANG II-treated fibroblasts. DETC also reduced the intracellular generation of reactive oxygen species (ROS) (such as H2O2, hydroxyl radicals, hydroperoxides) in control and ANG II-treated fibroblasts, whereas tempol reduced the ROS production only in ANG II-treated fibroblasts. ANG II and DETC stimulated the collagen production and the collagen I and fibronectin content in fibroblasts. The SOD mimetics tempol and EUK-8 as well as PEG-SOD reduced the collagen production. ANG II and DETC stimulated the tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 levels, whereas tempol decreased the TIMP-2 content in control and ANG II-treated fibroblasts. Matrix metalloproteinase (MMP)-1 level was reduced by ANG II and DETC and increased by tempol. Conclusion These data suggest a vital role of SOD and the formed ROS in the accumulation of collagen in cardiac fibroblasts.

Objective Evidence of a genetic basis of metabolic risk factors (MRFs) is growing. Studies examining the genetic and environmental basis of the clustering of MRFs, grouped together in the metabolic syndrome (MetS), are however sparse. The aim of this study therefore was to study the heritabilities of the MRFs and the genetic and environmental correlations between the MRFs. Methods Study participants were 768 Caucasian twins coming from 418 pairs (18–34 years). MRFs were those included in the National Cholesterol Education Program Adult Treatment Panel III definition of the MetS. Multivariate path analysis on the continuous MRFs of the MetS was implemented. Results Heritabilities ranged between 47.0% and 80.2% (men) and 58.5% and 77.9% (women) for the individual MRFs. Evidence was found for overarching genetic (A) and environmental (E) sources of variance, both however loading mainly on waist circumference. Furthermore, the model included a ‘lipids’ and a ‘blood pressure’-factor both in part attributable to A and E. The majority of the variance however was MRF-specific. Conclusion Based on our sample of young adults with a low prevalence of the MetS, it can be concluded that both genes and environment contribute significantly to the clustering of the MRFs although the majority of the variation is MRF-specific. Therefore, future QTL searches in young adults may want to focus on MRF-specific loci, rather than ‘cluster-phenotypes’ such as the MetS.

Children born small for gestational age are at increased risk of developing type 2 diabetes in adulthood. The satiety signal leptin that regulates food intake and energy expenditure might be a possible molecular link, as umbilical cord leptin levels are positively correlated with birth weight. In the present study, we examined whether common single nucleotide polymorphisms (SNPs) in the leptin (LEP; 19G>A) gene and its receptor (LEPR; Q223R and K109R) are associated with birth weight and adult metabolic risk factors for type 2 diabetes in twins.SNPs were genotyped in 396 monozygotic and 232 dizygotic twins (286 men and 342 women, mean age 25 years) recruited from the East Flanders Prospective Twin Survey. Data were analysed using linear mixed models.The LEPR K109R SNP was associated with birth weight (KK, KR and RR (95% confidence interval, CI): 2511 (2465-2557), 2575 (2516-2635) and 2726 (2606-2845) gram; P(additive)=0.001). Also the LEPR Q223R SNP showed a significant association with weight at birth (QQ, QR and RR (95% CI): 2492 (2431-2554), 2545 (2495-2595) and 2655 (2571-2740) gram; P(additive)=0.003). Furthermore, an interaction between the LEPR K109R and the Q223R SNP on birth weight was observed (P=0.014). G allele carriers of the LEP 19G>A SNP had higher high-density lipoprotein (HDL) cholesterol levels compared to 19A homozygotes (GX vs AA (95% CI): 1.62 (1.58-1.66) vs 1.49 (1.40-1.58) mmol l(-1); P(recessive)=0.013).This study indicates that leptin may act as a growth-promoting signal during fetal development, and suggests a possible role for the LEPR in explaining the inverse relationship between birth weight and the development of metabolic diseases in adulthood. Additionally, these results suggest that the LEP 19G>A SNP affect HDL cholesterol levels.

Recent guidelines recommend lifestyle measures, with physical activity as an integral component, for all patients with hypertension or prehypertension to lower blood pressure and control other risk factors. This review discusses both acute and long-term effects of dynamic aerobic endurance exercise and resistance exercise as nonpharmacologic tools to reduce blood pressure, respectively. The optimal exercise characteristics to lower blood pressure need to be more precisely defined, especially with regard to resistance exercise; so far, these effects have been shown to be immediate and elicited by low-intensity short-duration exercise. Based on the current evidence, hypertensive patients should be recommended to exercise on most, preferably all, days of the week, with moderate intensity (40% to 60% of VO2 reserve) for at least 30 minutes of continuous or accumulated physical activity per day, consisting primarily of endurance training but supplemented by resistance training.

Aims/hypothesis We determined the genetic contribution of 18 anthropometric and metabolic risk factors of type 2 diabetes using a young healthy twin population. Methods Traits were measured in 240 monozygotic (MZ) and 138 dizygotic (DZ) twin pairs aged 18 to 34 years. Twins were recruited from the Belgian population-based East Flanders Prospective Twin Survey, which is characterised by its accurate zygosity determination and extensive collection of perinatal and placental data, including information on chorionicity. Heritability was estimated using structural equation modelling implemented in the Mx software package. Results Intra-pair correlations of the anthropometric and metabolic characteristics did not differ between MZ monochorionic and MZ dichorionic pairs; consequently heritabilities were estimated using the classical twin approach. For body mass, BMI and fat mass, quantitative sex differences were observed; genetic variance explained 84, 85 and 81% of the total variation in men and 74, 75 and 70% in women, respectively. Heritability estimates of the waist-to-hip ratio, sum of four skinfold thicknesses and lean body mass were 70, 74 and 81%, respectively. The heritability estimates of fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance and beta cell function, as well as insulin-like growth factor binding protein-1 levels were 67, 49, 48, 62 and 47%, in that order. Finally, for total cholesterol, LDL-cholesterol, HDL-cholesterol, total cholesterol:HDL-cholesterol ratio, triacylglycerol, NEFA and leptin levels, genetic factors explained 75, 78, 76, 79, 58, 37 and 53% of the total variation, respectively. Conclusions/interpretation Genetic factors explain the greater part of the variation in traits related to obesity, glucose intolerance/insulin resistance and dyslipidaemia. Electronic supplementary material The online version of this article (doi:10.1007/s00125-007-0784-z) contains supplementary material, which is available to authorised users.

The 1996 American Heart Association consensus panel recommendations stated that pre-participation cardiovascular screening for young competitive athletes is justifiable and compelling on ethical, legal, and medical grounds. The present article represents the consensus statement of the Study Group on Sports Cardiology of the Working Group on Cardiac Rehabilitation and Exercise Physiology and the Working Group on Myocardial and Pericardial diseases of the European Society of Cardiology, which comprises cardiovascular specialists and other physicians from different European countries with extensive clinical experience with young competitive athletes, as well as with pathological substrates of sudden death. The document takes note of the 25-year Italian experience on systematic pre-participation screening of competitive athletes and focuses on relevant issues, mostly regarding the relative risk, causes, and prevalence of sudden death in athletes; the efficacy, feasibility, and cost-effectiveness of population-based pre-participation cardiovascular screening; the key role of 12-lead ECG for identification of cardiovascular diseases such as cardiomyopathies and channelopathies at risk of sudden death during sports; and the potential of preventing fatal events. The main purpose of the consensus document is to reinforce the principle of the need for pre-participation medical clearance of all young athletes involved in organized sports programmes, on the basis of (i) the proven efficacy of systematic screening by 12-lead ECG (in addition to history and physical examination) to identify hypertrophic cardiomyopathy-the leading cause of sports-related sudden death-and to prevent athletic field fatalities; (ii) the potential screening ability in detecting other lethal cardiovascular diseases presenting with ECG abnormalities. The consensus document recommends the implementation of a common European screening protocol essentially based on 12-lead ECG.

The heart is a major site of natriuretic peptides (NP). Atrial and brain natriuretic peptide (ANP and BNP) are predominantly produced by atria and ventricles. C-Natriuretic peptide (CNP) is also found in heart tissue. ANP and BNP are produced by cardiomyocytes and fibroblasts. Cardiac fibroblasts also secrete CNP. Three NP-receptors (NPR-A, NPRB, NPR-C) are expressed in heart atria and ventricles. Baseline plasma BNP is a sensitive predictor of morbidity and mortality in heart failure and changes in BNP over time are associated with corresponding changes in subsequent mortality and morbidity. Plasma BNP, and to a lesser extent ANP, is also a strong cardiovascular risk marker in patients with essential hypertension and left ventricular hypertrophy without left ventricle dysfunction or overt renal disease. However, evidence to date suggests that plasma BNP levels should not be viewed as a diagnostic test for chronic heart failure and sequential assays of BNP have not been shown to be useful in the follow-up or the initiation of appropriate therapy. However, patients who present with dyspnea with unclear but suspected cardiac etiologies may be considered to have venous blood taken for the measurement of BNP level to assist with diagnostic decision and therefore appropriate management of the dyspnea. BNP level is however not a stand-alone test and must be used in conjunction with careful clinical evaluation and in patients with an intermediate pre-test likelihood of heart failure.

The purpose of this investigation was to determine whether aminopeptidase inhibition could affect the angiotensin II-stimulated collagen gel contraction in basal (control) and TGF-beta1-treated cardiac fibroblasts (or myofibroblasts). The tested aminopeptidase inhibitors were the broad range aminopeptidase inhibitor bestatin, the specific inhibitor of alanine aminopeptidase leuhistin, and the specific inhibitor of arginine aminopeptidase arphamenine A. Cardiac fibroblasts (from normal male adult rats) from passage 2 were cultured to confluency and incubated with(out) 400 pmol/L TGF-beta1 in Dulbecco Modified Eagle Medium (DMEM) with 10% fetal bovine serum (FBS). These fibroblasts were then further incubated in a floating collagen gel lattice with the tested products (angiotensin II, bestatin, leuhistin, or arphamenine A) for 3 days in DMEM without FBS. The contraction of the collagen gel lattice by cardiac fibroblasts was determined by measuring the gel volume with tritiated water. Aminopeptidase activity was estimated by spectrophotometric determination of the liberation of p-nitroaniline from alanine- or arginine-p-nitroanilide. Angiotensin II (100 nmol/L) reduced the gel volume in control and TGF-beta1-treated cardiac fibroblasts. The angiotensin II-stimulated collagen gel contraction in control and TGF-beta1-treated fibroblasts was almost completely reversed by leuhistin and arphamenine A (100 micromol/L). Bestatin (100 micromol/L) only partially inhibited the angiotensin II-stimulated collagen gel contraction in control fibroblasts, although it did not affect the angiotensin II-induced contraction in TGF-beta1-treated fibroblasts. In control and TGF-beta1-treated cardiac fibroblasts, 100 micromol/L leuhistin or arphamenine A only partially inhibited alanine aminopeptidase activity, whereas bestatin (100 micromol/L) completely inhibited the alanine aminopeptidase activity. Arginine aminopeptidase activity was only partially inhibited by leuhistin and arphamenine A at 100 micromol/L in control and TGF-beta1-treated fibroblasts. Bestatin, however, completely blocked the arginine aminopeptidase activity in control fibroblasts and only partially in TGF-beta1-treated fibroblasts at 100 micromol/L. Our data suggest that both alanine and arginine aminopeptidases are involved in the reversal of the angiotensin II-stimulated collagen gel contraction in control and TGF-beta1-treated cardiac fibroblasts or myofibroblasts.

BACKGROUND: Risk factors in young adulthood may persist into later life and eventually lead to cardiovascular (CV) disease. The purpose of this study was to describe the prevalence of hypertension and other established CV risk factors in older adolescents. METHODS: Study nurses examined 120 girls and 80 boys with a mean age of 17.4 (SD, 0.8; range 15.8-19.6 years). After 5 minutes of sitting rest, resting blood pressure (BP) of the participants was measured in triplicate by sphygmomanometry. Body height and weight were measured and body mass index (BMI) was calculated. Serum lipids, smoking and drinking status were assessed. Hypertension was diagnosed according to the criteria specified in the 1996 update of the Task Force on BP treatment in Children and Adolescents (Pediatrics 1996;98:649-58). RESULTS: Almost 25% of the subjects currently smoked with a median daily consumption of 6 (Interquartile 4-9) and 11 (6-16) cigarettes in girls and boys, respectively. Fourty-nine (41%) girls used oral contraceptives. Systolic (118 versus 109 mm Hg, p25.0 kg/m2). Twenty (17%) girls and seven (9%) boys had hypercholesterolemia (total serum cholesterol > or =5.2 mmol/L). Overall, 50 (42%) girls and 31 (39%) boys had at least one CV risk factor, 12 (10%) girls and four (5%) boys had two risk factors, and three (3%) girls and one (1%) boy had more than two risk factors. CONCLUSIONS: In 17-year-olds living in an affluent society the prevalence of CV risk factors was high. These findings underscore the importance of health education and prevention at this age. ispartof: European journal of public health vol:14 issue:4 pages:361-5 ispartof: location:England status: published

White-coat hypertension (WCHT), also called 'isolated office or clinic hypertension', is defined as the occurrence of blood pressure (BP) values higher than normal when measured in the medical environment, but within the normal range during daily life, usually defined as average daytime ambulatory BP (ABP) or home BP values (

OBJECTIVE: In a prospective analysis of a Caucasian population, we recently found that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), alpha-adducin (Gly460Trp) and aldosterone synthase (-344C/T) jointly influence the incidence of hypertension. We therefore investigated the association between blood pressure and these three genes in a Chinese population. METHODS: We genotyped 479 Han Chinese from 125 nuclear families recruited in northern China via random sampling (approximately 75%) and at specialized hypertension clinics (approximately 25%). We performed population-based and family-based association analyses using generalized estimating equations (GEE) and the quantitative transmission disequilibrium test (QTDT), respectively, while controlling for covariables. RESULTS: The participants included 239 (49.9%) women and 132 (27.6%) hypertensive patients, of whom 77 took antihypertensive drugs. The blood pressure, measured at the subjects' homes, averaged 126/80 mmHg. Mean values of urinary sodium, potassium and Na/K ratio were 226 mmol/day, 37 mmol/day and 6.31, respectively. In adjusted GEE analyses, systolic blood pressure was 9.3 mmHg (95% confidence interval 3.6-15.0 mmHg; P = 0.001) and 14.6 mmHg (95% confidence interval 3.4-25.8 mmHg; P = 0.01) higher in the ACE DD than II subjects among the alpha-adducin TrpTrp (n = 141) and aldosterone synthase CC (n = 33) homozygotes, respectively (P < or =0.05 for interactions of the ACE genotype with the alpha-adducin and aldosterone synthase polymorphisms). Among 40 informative offspring homozygous for the alpha-adducin Trp allele, systolic blood pressure was significantly associated with transmission of the ACE D allele (beta = 5.5 mmHg; P = 0.046). CONCLUSIONS: The ACE I/D, alpha-adducin Gly460Trp and aldosterone synthase -344C/T polymorphisms interact to influence systolic blood pressure in Chinese, suggesting that these genes might indeed predispose to hypertension, especially in an ecogenetic context characterized by a high salt intake. ispartof: Journal of Hypertension vol:22 issue:5 pages:937-944 ispartof: location:Netherlands status: published

Background To assess the impact of immediate versus delayed anti hypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double- blind placebo-controlled Systolic Hypertension in Europe (Syst- Eur) trial by an open-label follow-up study lasting 4 years. Methods The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double- blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open- label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5 - 25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up. Results Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed anti hypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P=0.01) and 15% (P=0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively. Conclusions Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension. J Hypertens 22:847 -857 (C) 2004 Lippincott Williams Wilkins.

SUMMARY Hypertension (HTN), one of the most common medical disorders, is associated with an increased incidence of all-cause and cardiovascular disease (CVD) mortality. Lifestyle modifications are advocated for the prevention, treatment, and control of HTN, with exercise being an integral component. Exercise programs that primarily involve endurance activity prevent the development of HTN and lower blood pressure (BP) in adults with normal BP and those with HTN. The BP lowering effects of exercise are most pronounced in people with HTN who engage in endurance exercise with BP decreasing approximately 5–7 mm Hg after an isolated exercise session (acute) or following exercise training (chronic). Moreover, BP is reduced for up to 22 h after an endurance exercise bout (e.g., postexercise hypotension), with the greatest decreases among those with the highest baseline BP. The proposed mechanisms for the BP lowering effects of exercise include neurohumoral, vascular, and structural adaptations. Decreases in catecholamines and total peripheral resistance, improved insulin sensitivity, and alterations in vasodilators and vasoconstrictors are some of the postulated explanations for the antihypertensive effects of exercise. Emerging data suggest genetic links to the BP reductions associated with acute and chronic endurance exercise. Nonetheless, definitive conclusions regarding the mechanisms for the BP reductions following endurance exercise cannot be made at this time. Individuals with controlled HTN and no CVD or renal complications may participate in an exercise program or competitive athletics, but should be evaluated, treated, and monitored closely. Preliminary peak or symptom-limited exercise testing may be warranted, especially for men over 45 and women over 55 yr planning a vigorous exercise program (i.e., 60% u VO2R, oxygen uptake reserve). In the interim, while formal evaluation and management are taking place, it is reasonable for the majority of patients to begin moderate intensity exercise training (40 –60% u VO2R) such as walking. When pharmacologic therapy is indicated in physically active people it should, ideally: a) lower BP at rest and during exertion; b) decrease total peripheral resistance; and, c) not adversely affect exercise capacity. For these reasons, angiotensin converting enzyme (ACE) inhibitors (or angiotensin II receptor blockers in case of ACE inhibitor intolerance) and calcium channel blockers are currently the drugs of choice for recreational exercisers and athletes who have HTN. Exercise remains a cornerstone therapy for the primary prevention, treatment, and control of HTN. The optimal training frequency, intensity, time, and type (FITT) need to be better defined to optimize the BP lowering capacities of exercise, particularly in children, women, older adults, and

Cardiac enlargement in athletes was already recognised by the end of the 19th century through percussion of the chest in cross country skiers, and was later confirmed by use of radiography and evidence from necropsy. The advent of echocardiography allowed investigators to gain a better insight into the heart of athletes, and these findings were in general confirmed by other techniques such as magnetic resonance imaging. The present review will focus on the impact of different sports and training on cardiac structure and function, and on electrocardiographic alterations associated with athlete’s heart. ### Left ventricle #### Cross sectional studies Physical exercise is associated with haemodynamic changes and alters the loading conditions of the heart. In dynamic exercise the emphasis is on movement with no or minimal development of force. The main haemodynamic features are increases in heart rate and stroke volume, the two components of cardiac output. Systemic vascular resistance drops but the net result is a slight to moderate rise in blood pressure. The load on the heart is predominantly that of volume. In static exercise force is developed with no or minimal movement. The haemodynamic consequences involve a slight elevation of cardiac output, caused by the increase of heart rate, and a more pronounced rise of blood pressure, resulting in a pressure load on the heart. From a theoretical point of view the haemodynamic alterations and the ventricular loading conditions during exercise could, in the long run, lead to left ventricular hypertrophy (LVH). Volume load would lead to enlargement of the left ventricular internal diameter and a proportional increase of wall thickness; this type of adaptation is termed eccentric LVH. The pressure load would induce thickening of the ventricular wall with unchanged internal dimension, or concentric LVH. It was suggested that these cardiac adaptations serve to normalise wall stress. Individual studies showed that cardiac adaptations …

OBJECTIVE: To investigate whether baseline systolic blood pressure variability was a risk factor for stroke, cardiovascular mortality or cardiac events during the Syst-Eur trial. DESIGN: The Syst-Eur study was a randomized, double-blind, placebo-controlled trial, powered to detect differences in stroke rate between participants on active antihypertensive treatment and placebo. Systolic blood pressure variability measurements were made on 744 participants at the start of the trial. Systolic blood pressure variability was calculated over three time frames: 24 h, daytime and night-time. The placebo and active treatment subgroups were analysed separately using an intention-to-treat principle, adjusting for confounding factors using a multiple Cox regression model. PARTICIPANTS: An elderly hypertensive European population. MAIN OUTCOME MEASURES: Stroke, cardiac events (fatal and non-fatal heart failure, fatal and non-fatal myocardial infarction and sudden death) and cardiovascular mortality (death attributed to stroke, heart failure, myocardial infarction, sudden death, pulmonary embolus, peripheral vascular disease and aortic dissection). RESULTS: The risk of stroke increased by 80% (95% confidence interval: 17-176%) for every 5 mmHg increase in night-time systolic blood pressure variability in the placebo group. Risk of cardiovascular mortality and cardiac events was not significantly altered. Daytime variability readings did not predict outcome. Antihypertensive treatment did not affect systolic blood pressure variability over the median 4.4-year follow-up. CONCLUSION: In the placebo group, but not the active treatment group, increased night-time systolic blood pressure variability on admission to the Syst-Eur trial was an independent risk factor for stroke during the trial. ispartof: Journal of hypertension vol:21 issue:12 pages:2251-7 ispartof: location:Netherlands status: published

Influence of chorionicity on the heritability estimates of blood pressure: a study in twins.Fagard RH, Loos RJ, Beunen G, Derom C, Vlietinck R.Hypertension and Cardiovascular Rehabilitation Unit, Faculty of Medicine, University of Leuven, KU Leuven, Belgium. robert.fagard@uz.kuleuven.ac.beBACKGROUND: A basic assumption of the twin design is that environmental influences including prenatal experiences are equal across twin types. However, the intra-uterine environment may differ according to the chorionicity of the monozygotic twins, which may have biased previous heritability estimates of blood pressure. OBJECTIVE: The aim of the present study was to assess whether the heritability of blood pressure, derived from measurements in monozygotic and dizygotic twins, differs according to the chorionicity of the monozygotic twins. METHODS: Conventional and 24-h ambulatory blood pressures were measured in 125 dizygotic twin pairs and in 97 dichorionic and 128 monochorionic monozygotic twin pairs at the age of 18-34 years. The twin sample was drawn from the East Flanders Prospective Twin Survey, in which perinatal data were collected at birth. Intra-pair correlation coefficients were calculated and compared between both types of monozygotic twin pairs. Heritability was estimated from model-fitting and path analysis, based on the dizygotic twins and, respectively, all monozygotic twins and the two subtypes. RESULTS: Intra-pair correlation coefficients for the various blood pressures, after adjustment for body mass index, ranged from 0.45 to 0.71 in the monozygotic twin pairs and did not differ significantly according to chorionicity. Heritability estimates of blood pressure were between 52 and 64%, and were similar when calculated from dizygotic twins and, respectively, dichorionic and monochorionic monozygotic twins. CONCLUSIONS: Heritability estimates of conventional and ambulatory blood pressure do not differ significantly according to the chorionicity of the monozygotic twins.

Discordant findings are reported on the left ventricular transforming growth factor-beta(1) (TGF-beta(1)) mRNA levels in various rat models. Left ventricular TGF-beta(1) mRNA levels did not differ between spontaneously hypertensive rats (SHR) and normal rats, between deoxycorticosterone (DOCA)-salt and sham-operated hypertensive rats, but were increased in stroke-prone spontaneously hypertensive rats (SHRSP) and in post-myocardial infarction (MI) rats. Renal cortical TGF-beta(1) mRNA levels were, however, higher in DOCA-salt hypertensive rats. Angiotensin II subtype 1 receptor antagonism (AT(1)R) and angiotensin converting enzyme inhibition (ACEI) decreased left ventricular and vascular smooth muscle TGF-beta(1) mRNA levels in SHR and renal TGF-beta(1) mRNA in DOCA-salt hypertensive rats and in SHRSP. In post-MI rats ventricular TGF-beta(1) mRNA decreased by AT(1)R antagonism. In essential hypertensive patients, TGF-beta(1) protein as well as TGF-beta(1) mRNA levels are hyperexpressed. The TGF-beta(1) overproduction in hypertension can be attributed to various factors such as elevated angiotensin II, increased systemic blood pressure (BP) per se, increased fluid shear stress and a differential expression of TGF-beta(1) linked to DNA polymorphism in the promoter. The Arg(25) polymorphism in the TGF-beta(1) gene is associated with higher BP. A higher plasma TGF-beta(1) concentration is found in hypertensive patients with microalbuminuria and left ventricle hypertrophy. In these patients, AT(1)R antagonism and ACEI reduced these plasma TGF-beta(1) levels significantly.

ObjectiveMyofibroblasts and transforming growth factor-β1(TGF-β1) are key elements of cardiac tissue fibrosis development. The aim of this study was to determine whether the ability of TGF-β1to affect the contractile activity of cardiac fibroblasts depends on their differentiation into myofibroblasts.MethodsCardiac fibroblasts (from male adult Wistar rats) from passage two were cultured to confluency and incubated on a hydrated collagen gel with and without TGF-β1(0, 20, 40, 100, 200, 400 or 600 pmol/L) for one, two and three days in a Dulbecco's Modified Eagle's Medium without foetal bovine serum.ResultsTGF-β1dose-dependently increased the contraction of collagen gel mediated by cardiac fibroblasts, reaching a maximal effect at 100 pmol/L TGF-β1. TGF-β 1 also stimulated3H-thymidine incorporation and total protein content in cardiac fibroblasts in the collagen gel lattice . TGF-β1dose-dependently induced an increase in αsmooth muscle actin, a marker of myofibroblasts. The TGF-β1-induced reduction of area of the collagen gel was negatively correlated to the TGF- R β1-evoked appearance of α-smooth muscle actin in the collagen gel matrix.ConclusionOur data demonstrate that TGF-β1increased the contractile activity of adult rat cardiac fibroblasts and their ability to differentiate into myofibroblasts. Because contractile activity was correlated with differentiation, the influence of TGF-β1on cardiac fibroblast-induced collagen gel contraction might depend on the promotion of myofibroblast differentiation.

We examined to what extent self-measurement of blood pressure at home (HBP) can be an alternative to ambulatory monitoring (ABP) to diagnose white-coat hypertension.In 247 untreated patients, we compared the white-coat effects obtained by HBP and ABP. The thresholds to diagnose hypertension wereor = 140/or = 90 mmHg for conventional blood pressure (CBP) andor = 135/or = 85 mmHg for daytime ABP and HBP.Mean systolic/diastolic CBP, HBP and ABP were 155.4/100.0, 143.1/91.5 and 148.1/95.0 mmHg, respectively. The white-coat effect was 5.0/3.5 mmHg larger on HBP compared with ABP (12.3/8.6 versus 7.2/5.0 mmHg; P0.001). The correlation coefficients between the white-coat effects based on HBP and ABP were 0.74 systolic and 0.60 diastolic (P0.001). With ABP as a reference, the specificity of HBP to detect white-coat hypertension was 88.6%, and the sensitivity was 68.4%.Our findings are in line with the recommendations of the ASH Ad Hoc Panel that recommends HBP for screening while ABP has a better prognostic accuracy.

Markers for cardiovascular disease in monozygotic twins discordant for the use of third-generation oral contraceptives.Loos RJ, Verhaeghe J, De Zegher F, Beunen G, Derom C, Fagard R, Mathieu C, Vlietinck R.Department of Sport and Movement Sciences, Faculty of Physical Education and Physiotherapy, Katholieke Universiteit Leuven, 3000 Leuven, Belgium. loosr@pbrc.eduOral contraceptives (OC) modulate the risk for developing cardiovascular (CV) diseases. The aim of this study was to determine whether the use of third-generation OC has an impact on markers of CV disease in genetically identical women. We performed an intrapair comparison in 27 monozygotic twin pairs, one of whom was taking third-generation OC, whereas the other was not using OC. Biometric parameters were ascertained and conventional and 24-h ambulatory blood pressure (BP) was recorded. A fasting blood sample was taken for the measurement of glucose, insulin, proinsulin, lipids, and insulin-like growth factor binding protein-1 (IGFBP-1). Insulin resistance and beta-cell function were calculated by homeostasis model assessment (HOMA). A 24-h urine sample for cortisol was obtained. Third-generation OC use increased 24-h ambulatory systolic and diastolic BP by 5.2 and 3.9 mmHg, respectively (both P=0.0003). There was no effect on glucose, insulin and proinsulin levels, and on HOMA parameters, but the IGFBP-1 levels were markedly raised (P=0.0009). The lipid profile showed a 34% increase in triglyceride levels (P < 0.0001), but also a 7% increase in HDL-cholesterol levels (P=0.037). Use of third-generation OC impacts on CV disease markers in young-adult genetically identical women. Some changes are beneficial (increased HDL-cholesterol), whereas others may be deleterious (increased BP and triglyceride levels) or have unknown effects at this time (increased IGFBP-1 levels).

Depression is an independent risk factor in the pathogenesis of cardiovascular disease and it is a prevalent disorder after cardiovascular disease associated with negative outcome in terms of mortality and morbidity. It is a dangerous condition requiring adequate screening and treatment, however, it often remains undiagnosed and thus untreated. Non-psychiatric healthcare workers, like nurses, general practitioners, physiotherapists and cardiologists are the health providers most closely involved in the management of patients with cardiovascular disease. They can play an important role in screening cardiovascular patients for depressive symptoms and in referring them for treatment. The purpose of this article therefore is to provide an evidence-based framework, aiming to educate non-psychiatric healthcare providers on depressive disorder in the context of chronic cardiovascular disease. In this paper, an overview of the definition, prevalence and consequences of depression will be discussed. Moreover, an overview of measurement methods and treatment modalities for depression will be provided. In addition, a step-by-step guide is provided in order to help non-psychiatric healthcare providers in dealing with depressed patients.

This study investigated host factors and environmental factors as potential determinants of polychlorinated aromatic hydrocarbons (PCAHs) in serum of adolescents. We recruited 200 participants (80 boys and 120 girls), with a mean age of 17.4 years (SD, 0.8), in Belgium from a rural control area (Peer) and from two polluted suburbs of Antwerp where a nonferrous smelter (Hoboken) and waste incinerators (Wilrijk) are located. We quantified polychlorinated biphenyls (PCBs; congeners 138, 153, and 180) in serum by gas chromatography and obtained the toxic equivalents (TEQs) of PCAHs in serum with the chemically activated luciferase gene expression bioassay (CALUX). Serum PCB concentration was higher in boys than in girls (1.67 vs. 1.02 nmol/L or 377 vs. 210 pmol/g serum lipids; p< 0.001). In the whole adolescent group, multiple regression showed that serum PCB concentration decreased 0.06 nmol/L per 1% increase in body fat content (p< 0.001) and increased 0.39 nmol/L and 0.14 nmol/L per 1 mmol/L increase in serum concentrations of triglycerides (p < 0.001) and cholesterol (p = 0.002), respectively. Host factors explained 44% of the serum PCB variance. In the same model, serum PCB concentration increased 0.14 nmol/L with 10 weeks of breast-feeding (p< 0.001) and 0.06 nmol/L with intake of 10 g animal fat per day (p < 0.001), and was associated with residence in the waste incinerator area (9% higher; p = 0.04); 11% of the variance could be explained by these environmental factors. The geometric mean of the serum TEQ value was similar in boys and girls (0.15 TEQ ng/L or 33.0 pg/g serum lipids). In multiple regression, TEQ in serum decreased 0.03 ng/L per centimeter increase in triceps skinfold (p = 0.006) and was 29% higher in subjects living close to the nonferrous smelter (p < 0.001). This study showed that in 16- to 18-year-old teenagers host factors are important determinants of serum concentrations of PCAHs, whereas environmentally related determinants may to some extent contribute independently to human exposure to these persistent chemicals in the environment. ispartof: Environmental health perspectives vol:110 issue:6 pages:583-9 ispartof: location:United States status: published

OBJECTIVES: To evaluate the association between birth weight and adult body composition in twins, controlling for maternal and genetic influences. DESIGN: Twins were randomly selected from the East Flanders Prospective Twin Survey, a population-based historic twin cohort. SUBJECTS: Male members of 229 twin pairs between 18 and 34 y of age who participated in the Prenatal Programming Twin Study. MEASUREMENTS: Adult body mass, height, BMI, lean body mass, sum of skinfolds and waist-to-hip-ratio. Lean body mass, sum of skinfolds and waist-to-hip-ratio were also adjusted for body mass. Intra-pair difference in adult anthropometric measures between the heaviest and the lightest twin at birth. RESULTS: Per kg increase in birth weight, body mass (4.2 kg), height (3.3 cm), lean body mass (3.1 kg) and to a lesser extent BMI (0.49 kg/m2) increased, whereas waist-to-hip-ratio (−1.4%) and sum of skinfolds (−0.11 s.d.) decreased, when adjusted for body mass. In a pair-wise analysis, the heavier twin at birth was taller and heavier as an adult, but, when adjusted for body mass, he had a lower waist-to-hip-ratio, less subcutaneous fat, and more lean body mass, compared to his lighter sib. Intra-pair difference in body composition was associated with intra-pair birth weight difference in monozygotic and dizygotic twins. CONCLUSIONS: An adverse intra-uterine environment, as measured by birth weight, is associated with more subcutaneous and abdominal fat and less lean body mass in adulthood. This association is independent of maternal and genetic influences. However, we cannot exclude the existence of genes that act on both birth weight and adult body composition.

The possible contributions of the angiotensin receptor subtypes 1 and 2 on the angiotensin II-induced collagen gel contraction by adult rat cardiac fibroblasts were studied using the specific angiotensin receptor type 1 and 2 antagonists telmisartan and P-186, respectively. Cardiac fibroblasts (from normal male adult rats) from passage 2 were cultured to confluency and added to a hydrated collagen gel, with or without angiotensin II, angiotensin II plus telmisartan, or angiotensin II plus P-186 in Dulbecco's Modified Eagle's Medium containing 5% fetal bovine serum for 1, 2, or 3 days. Control gels containing adult rat cardiac fibroblasts showed a significant amount of contraction after 3 days of incubation, causing a contraction to 67.9 +/- 7.1% of the area after 1 day. Angiotensin II (10(-7) M) stimulated (p < or = 0.05) the contraction of collagen mediated by cardiac fibroblasts after 1, 2, or 3 days. Telmisartan (10(-7) M) completely blocked the angiotensin II-induced collagen contraction by cardiac fibroblasts. P-186 (10(-7) M) had no effect on the angiotensin II-induced collagen contraction by cardiac fibroblasts. Addition of telmisartan and P-186 alone did not affect the collagen gel contraction by cardiac fibroblasts. Our data demonstrate that the effects of angiotensin II on the collagen gel contraction by adult rat cardiac fibroblasts are angiotensin II type 1 receptor mediated because they were abolished by the specific angiotensin II type 1 receptor antagonist telmisartan but not by the specific angiotensin II type 2 receptor antagonist P-186.

The aim of this preliminary study was to compare exercise performance and the effect of exercise training in cardiac patients with and without an implantable cardioverter-defibrillator (ICD). There are few data on exercise performance and on the effect of exercise training in patients with an ICD. Data in patients with an ICD (n = 8) were compared with those from a matched control group (n = 16). Patients performed maximal cycle-ergometer testing before and after 3 months of exercise training. All patients had to stop the exercise test for reasons of exhaustion. The predetermined heart rate threshold in ICD patients, set at the detection rate of the ICD minus 30 beats/min, was not reached. Before training, peak oxygen uptake was not different in the ICD patients compared with the control group (21.0 +/- 6.9 vs 21.9 +/- 5.0 ml oxygen standard temperature pressure dry/min/kg). Exercise training increased peak oxygen uptake to a similar extent in both groups, 20% and 24%, respectively. One ICD patient developed uneventful ventricular tachycardia at the end of the post-training exercise test, and another during training. Thus, exercise performance and the favorable response to a 3-month exercise training program are comparable in patients with ICD and matched control patients. However, tachyarrhythmias may occur during exercise testing or training and require special attention. Selected patients with ICD can be encouraged to participate in medically supervised exercise training programs. The results of this study should be confirmed with additional studies on larger numbers of subjects.

The primary objective of this randomised, placebo- controlled, double-blind, crossover study, was to evaluate and compare the longer term effects of the angiotensin II type 1 receptor antagonist losartan and the converting enzyme inhibitor enalapril on 24-h ambulatory blood pressure (BP). After a 4-week placebo run-in period, nine patients with essential hypertension entered the double-blind phase of the study, which consisted of three 6-week periods during which patients were treated with placebo, enalapril 20 mg o.d. or losartan 50 mg o.d. Losartan and enalapril, taken between 07.00 and 08.00, reduced ambulatory BP throughout the 24-h period. Average night time BP was reduced from 133/85 mm Hg on placebo to 124/78 mm Hg on enalapril and to 126/77 mm Hg on losartan. Daytime BP averaged 157/101 mm Hg on placebo, and was significantly lower during enalapril (142/91 mm Hg) than during losartan treatment (147/95 mm Hg). Clinic BP, measured 2 to 4 hours after drug intake, was reduced to the same extent by both drugs. The losartan-induced BP changes were significantly related to those obtained with enalapril (0.63 < r < 0.93). Ambulatory BP monitoring was repeated after 4 weeks of combined therapy in six patients. The BP lowering effect of the combination was not significantly better than that achieved with enalapril alone. In conclusion, losartan 50 mg o.d. and enalapril 20 mg o.d. lower BP to approximately the same extent, except for a more pronounced effect of enalapril on daytime ambulatory BP. The current study does not provide convincing evidence that addition of losartan to enalapril in the doses used further reduces BP.

This meta-analysis attempted to derive pooled estimates for the putative association between echocardiographic or electrocardiographic left ventricular hypertrophy and the deletion/insertion (D/I) polymorphism of the angiotensin-I converting enzyme. Case-control studies were combined, using the Mantel and Haenszel approach. Joint P-values for continuous variables were calculated by Stouffer's method. Continuous measurements of left ventricular mass, which were reported in different units, were expressed on a percentage scale using the within-study mean of the II genotype as the denominator. The computerised database used for this analysis, included 28 reports with an overall sample size of 6638 subjects. The prevalence of the D allele was significantly lower in Japanese (37.2%) than in Caucasians (56.2%). A funnel plot including 12 case-control studies (4094 subjects) suggested that no publication bias was present. Overall, left ventricular hypertrophy was not associated with the D allele. Compared with the II genotype, the excess risks of left ventricular hypertrophy associated with DD and DI genotypes were only 14% (95% CI: 0.92-1.42; P = 0.23) and 5% (95% CI: 0.87-1.28; P = 0.61), respectively. However, the sensitivity analysis showed that in untreated hypertensive patients the DD genotype, compared with II homozygozity, was associated with a 192% (P = 0.002) higher risk of left ventricular hypertrophy. If left ventricular mass was analysed as a continuous trait across 23 studies (5438 subjects), overall no association with the D/I polymorphism was present. However, if untreated hypertensive patients were analysed separately, echocardiographic left ventricular mass was on average 10.1% (95% CI: 4.8-15.5%; P = 0.001) higher in DDhomozygotes than in the II reference group. Thus, in untreated hypertensive patients, in case-control studies as well as association studies, the D allele behaved as a marker for left ventricular hypertrophy. These findings support the hypothesis that the enhanced ACE activity associated with the D allele may promote left ventricular hypertrophy if a pathophysiologic process causing this disorder, remains unopposed by treatment. ispartof: Journal of Human Hypertension vol:14 issue:7 pages:447-454 ispartof: location:England status: published

The objective was to assess the influence of a cardiac rehabilitation training session on blood pressure measured shortly after exercise and during the subsequent 24 h in patients with stable coronary artery disease. Blood pressure was measured conventionally and by use of 24-h ambulatory blood pressure monitoring in seven men, mean age 53+/-8 (s.d.) years, after participation in a cardiac rehabilitation session and, in randomised order, on a non-exercise control day. Conventional blood pressure averaged 112+/-7/77+/-5 mm Hg in the sitting position on the control day and was not different at the same time of the day shortly after the patients had participated in a cardiac rehabilitation training session. Standing systolic pressure was lower by 7.8+/-4.3 mm Hg (P < 0.005) after exercise compared to the control situation, but this was not associated with orthostatic symptoms. However, ambulatory monitoring showed no differences in blood pressure with the non-exercise day during the subsequent 24-h period. In conclusion, standing but not sitting blood pressure was slightly lower shortly after a cardiac rehabilitation session, but the postexercise orthostatic hypotension was not sustained during normal activities of daily living.

Summary Background 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 Methods 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. Findings 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). Interpretation 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.

Smoking is considered an important “risk factor” for arterial hypertension and diabetes management, according to, respectively, the current guidelines of the European Society of Hypertension and the European Society of Cardiology on the management of arterial hypertension (1) and the guidelines on diabetes of the European Society of Cardiology and the European Association for the Study of Diabetes (2). The aim of the current article is to further evaluate the effect of smoking on mortality and cause-specific cardiovascular events in hypertension and in diabetes and to assess whether there is a significant interaction between the effects of smoking and diabetes. To assess the effect of smoking on mortality and cause-specific cardiovascular events, and the interaction between smoking and diabetes, we analyzed a database of 3,468 hypertensive patients without major cardiovascular disease at baseline and with prospective follow-up for morbidity and mortality (3). The database consists of individual data of hypertensive patients from four prospective studies performed in Europe (4–7). Age of the subjects averaged 61 ± 13 years (mean ± SD), 45% were men, and 61% were under antihypertensive treatment at baseline. Office blood pressure averaged 159.0 ± 19.9/91.0 ± 11.7 mmHg and 24-h ambulatory blood pressure 138.1 ± 16.4/82.3 ± 11.0 mmHg. Current smoking and diabetes were coded as yes or no at the baseline examination; 13.7% of the patients smoked and 8.4% had diabetes. We used Cox proportional hazards regression analysis to assess the prognostic significance of smoking, with stratification for study and adjustment for age, sex, diabetes, total cholesterol, 24-h systolic blood pressure, antihypertensive treatment, and BMI. The average 24-h blood pressure was used because its predictive power has been shown to be superior to that of office blood pressure (3). Median follow-up time was 6.57 years (range 0.08–13.1) and total follow-up time amounted to …

Aims: Isolated systolic hypertension affects over 8 to 15% of all subjects older than 60 years. In the elderly, systolic hypertension is the major modifiable cardiovascular risk factor. Three placebo-controlled outcome trials on antihypertensive drug treatment of this disorder have been published. The aim of this article was to shortly review each of these three trials and to present the pooled estimates of benefit of antihypertensive drug treatment in isolated systolic hypertension in the elderly. Methods and results: The Systolic Hypertension in the Elderly Program (SHEP) in the United States, the Systolic Hypertension in Europe (Syst-Eur) trial and the Systolic Hypertension in China (Syst-China) trial published their main findings in 1991, 1997 and 1998, respectively. The outcome results of these trials were pooled by calculating the common odds ratio for active versus placebo treatment for five major end-points. Zelen's exact test for homogeneity did not reach statistical significance for any of the end-points considered. Thus, the hypothesis of a common underlying treatment effect across the three trials was not rejected. Overall, active treatment compared with placebo, reduced all-cause mortality by 17%, cardiovascular mortality by 25%, all cardiovascular end-points by 32%, total stroke by 37% and myocardial infarction including sudden death by 25%. Conclusions: The pooled results of the outcome trials in older patients with isolated systolic hypertension prove that antihypertensive drug treatment must be prescribed, if on repeated measurement systolic blood pressure is 160 mm Hg or higher.