Most guidelines for the management of patients with cardiovascular disease recommend angiotensin-converting enzyme (ACE) inhibitors as first-choice therapy, whereas angiotensin receptor blockers ...(ARBs) are merely considered an alternative for ACE inhibitor-intolerant patients. The aim of this review was to compare outcomes and adverse events between ACE inhibitors and ARBs in patients. In patients with hypertension and hypertension with compelling indications, we found no difference in efficacy between ARBs and ACE inhibitors with regard to the surrogate endpoint of blood pressure and outcomes of all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. However, ACE inhibitors remain associated with cough and a very low risk of angioedema and fatalities. Overall withdrawal rates because of adverse events are lower with ARBs than with ACE inhibitors. Given the equal outcome efficacy but fewer adverse events with ARBs, risk-to-benefit analysis in aggregate indicates that at present there is little, if any, reason to use ACE inhibitors for the treatment of hypertension or its compelling indications.
Assisted reproductive technology (ART) involves the manipulation of early embryos at a time when they may be particularly vulnerable to external disturbances. Environmental influences during the ...embryonic and fetal development influence the individual's susceptibility to cardiovascular disease, raising concerns about the potential consequences of ART on the long-term health of the offspring.
We assessed systemic (flow-mediated dilation of the brachial artery, pulse-wave velocity, and carotid intima-media thickness) and pulmonary (pulmonary artery pressure at high altitude by Doppler echocardiography) vascular function in 65 healthy children born after ART and 57 control children. Flow-mediated dilation of the brachial artery was 25% smaller in ART than in control children (6.7 ± 1.6% versus 8.6 ± 1.7%; P<0.0001), whereas endothelium-independent vasodilation was similar in the 2 groups. Carotid-femoral pulse-wave velocity was significantly (P<0.001) faster and carotid intima-media thickness was significantly (P<0.0001) greater in children conceived by ART than in control children. The systolic pulmonary artery pressure at high altitude (3450 m) was 30% higher (P<0.001) in ART than in control children. Vascular function was normal in children conceived naturally during hormonal stimulation of ovulation and in siblings of ART children who were conceived naturally.
Healthy children conceived by ART display generalized vascular dysfunction. This problem does not appear to be related to parental factors but to the ART procedure itself.
URL: www.clinicaltrials.gov. Unique identifier: NCT00837642.
Longstanding hypertension ultimately leads to heart failure (HF), and, as a consequence most patients with HF have a history of hypertension. Conversely, absence of hypertension in middle age is ...associated with lower risks for incident HF across the remaining life course. Cardiac remodeling to a predominant pressure overload consists of diastolic dysfunction and concentric left ventricular (LV) hypertrophy. When pressure overload is sustained, diastolic dysfunction progresses, filling of the concentric remodeled LV decreases, and HF with preserved ejection fraction ensues. Diastolic dysfunction and HF with preserved ejection fraction are the most common cardiac complications of hypertension. The end stage of hypertensive heart disease results from pressure and volume overload and consists of dilated cardiomyopathy with both diastolic dysfunction and reduced ejection fraction. "Decapitated hypertension" is a term used to describe the decrease in blood pressure resulting from reduced pump function in HF. Progressive renal failure, another complication of longstanding hypertension, gives rise to the cardiorenal syndrome (HF and renal failure). The so-called Pickering syndrome, a clinical entity consisting of flash pulmonary edema and bilateral atheromatous renovascular disease, is a special form of the cardiorenal syndrome. Revascularization of renal arteries is the treatment of choice. Most antihypertensive drug classes when used as initial therapy decelerate the transition from hypertension to HF, although not all of them are equally efficacious. Low-dose, once-daily hydrochlorothiazide should be avoided, but long-acting thiazide-like diuretics chlorthalidone and indapamide seem to have an edge over other antihypertensive drugs in preventing HF.
Secondary hypertension refers to arterial hypertension due to an identifiable cause and affects ∼5–10% of the general hypertensive population. Because secondary forms are rare and work up is ...time-consuming and expensive, only patients with clinical suspicion should be screened. In recent years, some new aspects gained importance regarding this screening. In particular, increasing evidence suggests that 24 h ambulatory blood pressure (BP) monitoring plays a central role in the work up of patients with suspected secondary hypertension. Moreover, obstructive sleep apnoea has been identified as one of the most frequent causes. Finally, the introduction of catheter-based renal denervation for the treatment of patients with resistant hypertension has dramatically increased the interest and the number of patients evaluated for renal artery stenosis. We review the clinical clues of the most common causes of secondary hypertension. Specific recommendations are given as to evaluation and treatment of various forms of secondary hypertension. Despite appropriate therapy or even removal of the secondary cause, BP rarely ever returns to normal with long-term follow-up. Such residue hypertension indicates either that some patients with secondary hypertension also have concomitant essential hypertension or that irreversible vascular remodelling has taken place. Thus, in patients with potentially reversible causes of hypertension, early detection and treatment are important to minimize/prevent irreversible changes in the vasculature and target organs.
Abstract An elevated resting heart rate has been unequivocally linked to adverse cardiovascular events. Conversely, a physiologically low heart rate may confer longevity benefits. Moreover, ...pharmacological heart rate lowering reduces cardiovascular outcomes in patients with heart failure, with the magnitude of the reduction associated with survival benefit. In contrast, pharmacological heart rate lowering paradoxically increases cardiovascular events in hypertension, possibly because it elicits a ventricular-vascular mismatch, leading to increased central systolic blood pressure (BP). By the same hemodynamic mechanism, pharmacological heart rate lowering also engenders an increase in central (aortic) BP in coronary heart disease and, as a consequence, fails to decrease myocardial oxygen consumption. Whether in heart failure, hypertension, or coronary heart disease, or even athletes, heart rate lowering consistently increases central systolic pressure. The increase in central systolic BP is prone to abolish the potential benefits of heart rate lowering interventions, possibly accounting for failure to reduce outcomes in patients with hypertension and coronary artery disease.
Until recently, intraindividual visit-to-visit variability of cardiovascular risk factors has been dismissed as random fluctuation. This simplistic concept was challenged by demonstrating that ...visit-to-visit blood pressure variability, independent of average blood pressure, was a powerful risk factor for stroke. Subsequently, variability of other cardiovascular risk factors such as cholesterol, glycemia, and body weight was documented to increase risk independent of their absolute values. Variability of these risk factors has been demonstrated to be a powerful predictor for all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia. With the notable exception of heart rate, cardiovascular risk factors must now be defined by 2 components: the magnitude and duration of sustained risk factor elevation and, equally important, the variability of the same risk factor over time.
Epidemiological studies demonstrate a relationship between pathological events during foetal development and future cardiovascular risk and the term 'foetal programming of cardiovascular disease' has ...been coined to describe this phenomenon. The use of assisted reproductive technologies (ARTs) is growing exponentially and 2-5% of children are now born by this procedure. Emerging evidence indicates that ART represents a novel important example of foetal programming. Assisted reproductive technology may modify the cardiovascular phenotype in two ways: (i) ART involves manipulation of the early embryo which is exquisitely sensitive to environmental insults. In line with this concern, ART alters vascular and cardiac function in children and studies in mice show that ART alters the cardiovascular phenotype by epigenetic alterations related to suboptimal culture conditions. (ii) Assisted reproductive technology markedly increases the risk of foetal insults that augment cardiovascular risk in naturally conceived individuals and are expected to have similar consequences in the ART population. Given the young age of the ART population, it will take another 20-30 years before data on cardiovascular endpoints will be available. What is clear already, however, is that ART emerges as an important cardiovascular risk factor. This insight requires us to revise notions on ART's long-term safety and to engage on a debate on its future. There is an urgent need to better understand the mechanisms underpinning ART-induced alteration of the cardiovascular phenotype, improve the procedure and its long-term safety, and, while awaiting this aim, not to abandon medicine's fundamental principle of doing no harm (to future children) and use ART parsimoniously.
Assisted reproductive technologies (ART) predispose the offspring to vascular dysfunction, arterial hypertension, and hypoxic pulmonary hypertension. Recently, cardiac remodeling and dysfunction ...during fetal and early postnatal life have been reported in offspring of ART, but it is not known whether these cardiac alterations persist later in life and whether confounding factors contribute to this problem. We, therefore, assessed cardiac function and pulmonary artery pressure by echocardiography in 54 healthy children conceived by ART (mean age 11.5 ± 2.4 yr) and 54 age-matched (12.2 ± 2.3 yr) and sex-matched control children. Because ART is often associated with low birth weight and prematurity, two potential confounders associated with cardiac dysfunction, only singletons born with normal birth weight at term were studied. Moreover, because cardiac remodeling in infants conceived by ART was observed in utero, a situation associated with increased right heart load, we also assessed cardiac function during high-altitude exposure, a condition associated with hypoxic pulmonary hypertension-induced right ventricular overload. We found that, while at low altitude cardiac morphometry and function was not different between children conceived by ART and control children, under the stressful conditions of high-altitude-induced pressure overload and hypoxia, larger right ventricular end-diastolic area and diastolic dysfunction (evidenced by lower E-wave tissue Doppler velocity and A-wave tissue Doppler velocity of the lateral tricuspid annulus) were detectable in children and adolescents conceived by ART. In conclusion, right ventricular dysfunction persists in children and adolescents conceived by ART. These cardiac alterations appear to be related to ART per se rather than to low birth weight or prematurity.
Assisted reproductive technologies (ART) have been shown to induce premature vascular aging in apparently healthy children. In mice, ART-induced premature vascular aging evolves into arterial ...hypertension. Given the young age of the human ART group, long-term sequelae of ART-induced alterations of the cardiovascular phenotype are unknown.
This study hypothesized that vascular alterations persist in adolescents and young adults conceived by ART and that arterial hypertension possibly represents the first detectable clinically relevant endpoint in this group.
Five years after the initial assessment, the study investigators reassessed vascular function and performed 24-h ambulatory blood pressure (BP) monitoring (ABPM) in 54 young, apparently healthy participants conceived through ART and 43 age- and sex-matched controls.
Premature vascular aging persisted in ART-conceived subjects, as evidenced by a roughly 25% impairment of flow-mediated dilation of the brachial artery (p < 0.001) and increased pulse-wave velocity and carotid intima-media thickness. Most importantly, ABPM values (systolic BP, 119.8 ± 9.1 mm Hg vs. 115.7 ± 7.0 mm Hg, p = 0.03; diastolic BP, 71.4 ± 6.1 mm Hg vs. 69.1 ± 4.2 mm Hg, p = 0.02 ART vs. control) and BP variability were markedly higher in ART-conceived subjects than in control subjects. Eight of the 52 ART participants, but only 1 of the 43 control participants (p = 0.041 ART vs. controls) fulfilled ABPM criteria of arterial hypertension (>130/80 mm Hg and/or >95th percentile).
ART-induced premature vascular aging persists in apparently healthy adolescents and young adults without any other detectable classical cardiovascular risk factors and progresses to arterial hypertension. (Vascular Dysfunction in Offspring of Assisted Reproduction Technologies; NCT00837642.)
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Children conceived by assisted reproductive technologies (ART) display a level of vascular dysfunction similar to that seen in children of mothers with preeclamspia. The long-term consequences of ...ART-associated vascular disorders are unknown and difficult to investigate in healthy children. Here, we found that vasculature from mice generated by ART display endothelial dysfunction and increased stiffness, which translated into arterial hypertension in vivo. Progeny of male ART mice also exhibited vascular dysfunction, suggesting underlying epigenetic modifications. ART mice had altered methylation at the promoter of the gene encoding eNOS in the aorta, which correlated with decreased vascular eNOS expression and NO synthesis. Administration of a deacetylase inhibitor to ART mice normalized vascular gene methylation and function and resulted in progeny without vascular dysfunction. The induction of ART-associated vascular and epigenetic alterations appeared to be related to the embryo environment; these alterations were possibly facilitated by the hormonally stimulated ovulation accompanying ART. Finally, ART mice challenged with a high-fat diet had roughly a 25% shorter life span compared with control animals. This study highlights the potential of ART to induce vascular dysfunction and shorten life span and suggests that epigenetic alterations contribute to these problems.
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