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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The delineation of the molecular mechanisms of cardiovascular disease is an important initial step in developing improved methods of screening and therapy. Recently, progress has been made in characterizing the molecular basis of several inherited cardiovascular diseases, particularly as to the diseases caused by defects in single gene. When the disease under study has a complex etiology with multiple genetic and environmental components, it becomes much more difficult to dissect out the genetic factors and to distinguish between causation and correlation. Gene targeting in mice provides a means to test the effect of a precise genetic change completely free from the effects of differences in any other genes. Models of several human genetic diseases have been produced by gene targeting and the resulting "knockout" mice have often confirmed that the disease is the consequence of the defect of a gene of interest. The review will focus on the how molecular genetic approach is useful to understand the basic mechanism of complex genetic diseases, including essential hypertension, atherosclerosis, congenital heart disease. Particular emphasis will be given to the renin angiotensin system because a large body of evidence indicates its greater role in the pathogenesis of many complex cardiovascular diseases than has been recognized.
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PMID:Molecular genetic approach to the pathophysiology of cardiovascular disease. 897 74

There is abundant evidence that the atherosclerotic process begins in childhood. Dyslipidemia is a major risk factor for atherosclerosis in adults and children. In the present study, we measured serum lipoprotein concentrations in 194 healthy children aged between 4 to 14 years. Children were grouped according to the socioeconomic status of the families, family history of essential hypertension and passive tobacco exposure. The values of total cholesterol, low density lipoprotein cholesterol and the ratio of total cholesterol/high density lipoprotein cholesterol in the low socioeconomic group were found to be significantly higher than the values obtained for the middle-high socioeconomic group. The values of total cholesterol, low density lipoprotein cholesterol, the ratio of total cholesterol/high density lipoprotein cholesterol and low density lipoprotein cholesterol/high density lipoprotein cholesterol in the passive smoker group were found to be significantly higher than those of the nonsmoker group. But, the socioeconomic level in the passive smoker group was found to be significantly lower than that of the nonsmoker group, and therefore, the impact of passive smoking on the serum lipids in children was related to socioeconomic status. A significant difference in terms of blood lipid fractions between the groups with and that without a family history of essential hypertension was not found. These results suggest that passive smoking and lower socioeconomic status are important risk factors for cardiovascular heart disease, while a positive family history of essential hypertension is not an important risk factor.
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PMID:Effects of passive exposure to tobacco, socioeconomic status and a family history of essential hypertension on lipid profiles in children. 905 86

The patterns of interventricular septal hypertrophy were analyzed on two-dimensional echocardiograms to differentiate hypertrophic cardiomyopathy (HCM) from hypertensive cardiac hypertrophy. The control group comprised 110 patients without cardiovascular disease who were matched for age and gender with the hypertension group. The hypertension group comprised 110 patients with uncomplicated essential hypertension, and the HCM group comprised 32 patients in whom the wall thickness of the interventricular septum was 12 mm or more at the mid-portion and no underlying heart disease responsible for cardiac hypertrophy was detected. The interventricular septal thickness was measured both at the thickest portion within 15 mm distal to the aortoseptal junction (basal portion: B) and at the mid-portion (M) in the end-diastolic image on the left parasternal long-axis tomograms, and the B/M ratio was calculated in each patient. The B/M ratio was 1.07 +/- 0.16 in the control group, 1.19 +/- 0.18 in the hypertension group, and 0.83 +/- 0.12 in the HCM group. Compared with the control group, the B/M ratio was significantly high in the hypertension group (p < 0.05) and significantly low in the HCM group (p < 0.01). These results indicate that hypertrophy of the interventricular septum is dominant at the basal portion in hypertensive patients but at the mid-portion in patients with HCM.
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PMID:[Differentiation of hypertrophic cardiomyopathy and hypertensive cardiac hypertrophy using the patterns of interventricular septum hypertrophy]. 906 91

Pediatric epidemiology programs have established that the major adult cardiovascular (C-V) diseases, coronary-artery disease, and essential hypertension, begin in childhood. Cardiovascular risk factors change during periods of growth and development, and there are distinct ethnic (black-white) and male-female differences that relate to adult heart disease. These risk factors have been shown to "track" over a 15-year period and are predictive of adult levels. Secular trends show increasing adiposity in the general population of children; an overall weight gain of 2 kg occurred during the decade from the 1970s to the 1980s, and approximately 5 kg during the decade from the 1980s to the 1990s. In all likelihood, increasing obesity is related to a more sedentary lifestyle. Cardiovascular risk factors also tend to cluster, for example, obesity correlates with higher blood pressure and with adverse serum lipoprotein changes. Further, a central distribution of obesity clusters with multiple risk factors in the insulin-resistant syndrome. Importantly, antemortem risk factors relate to actual C-V lesions found at autopsy. Lesions of a progressive nature occur in coronary vessels, which can ultimately result in clinical coronary heart disease. The development of lesions lag in young women at an equivalent age and with similar levels of risk factors. In addition, ethnic differences are noted in the development of C-V changes related to atherosclerosis and hypertension. The demonstration of C-V disease in early life gives credibility to risk-factor examination of children and the need for beginning of prevention in early life.
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PMID:Precursors of cardiovascular risk in young adults from a biracial (black-white) population: the Bogalusa Heart Study. 923 88

Abnormalities in left ventricular (LV) diastolic function may be the earliest indications of hypertensive heart disease. Because the two ventricles influence each other's performance this study was designed to investigate the impact of chronic LV pressure overload in essential hypertension (HT) on diastolic function of right ventricle (RV). RV and LV diastolic function was evaluated in 74 patients with mild-to-moderate essential HT using pulsed wave Doppler echocardiography. Fifty-five normotensive patients without heart disease acted as control subjects. In studied group, 17 patients (23%) had normal mitral (MV) and tricuspid (TV) flow parameters, 28 (38%) had impaired LV filling parameters [MV early (E) to late (A) peak flow velocity ratio (MV E/A) 0.81 +/- 0.12 vs control 1.19 +/- 0.18, p < 0.001] while 29 patients (39%) had abnormal both mitral [MV E/A) 0.72 +/- 0.15 vs control 1.19 +/- 0.18, p < 0.001] and tricuspid flow parameters (TV E/A) 0.8 +/- 0.19 vs control 1.23 +/- 0.1, p < 0.001). In group with impaired diastolic filling of both ventricles indices of mitral flow were significantly more abnormal compared to group with normal TV flow parameters (MV E/A 0.72 +/- 0.15 vs control 0.81 +/- 0.12, p < 0.05). RV filling parameters correlated with filling parameters. There was good correlation between TV A and MV E (r = -0.56, p < 0.01), the time velocity integral of early mitral inflow (MV E-VTI) (r = -0.64, p < 0.001) and positive correlation with MV A (r = 0.78, p < 0.0001). Also there was good correlation between LV mass and TV E (r = -0.56, p < 0.01) and the time velocity integral of early tricuspid inflow (r = -0.72, p < 0.001). Data indicate that RV diastolic function is abnormal in essential hypertension and these abnormalities are closely related to those of LV diastolic function and LV mass.
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PMID:[Right ventricular diastolic disfunction and its relation to left ventricular performance in patients with hypertension]. 941 9

Because antihypertensive therapy is effective in elderly patients with isolated systolic hypertension, attention has been focused on the systolic blood pressure as a predictor of cardiovascular risk. However, it is a normal diastolic pressure that separates patients with isolated systolic hypertension from those with essential hypertension. The normal diastolic and elevated systolic pressures are largely due to age-related stiffening of the aorta. An indistensible aorta causes the pressure pulse to travel faster than normal, where it is quickly reflected off the peripheral resistance. The reflected wave then returns to the central aorta in systole rather than diastole. This augments the systolic pressure further, increasing cardiac work while reducing the diastolic pressure, on which coronary flow is dependent. The potential harm of further reducing the diastolic pressure with antihypertensive therapy, especially in patients with coronary heart disease, underlies the controversial "J curve." By decreasing the blood pressure, all antihypertensive agents improve aortic distensibility, but no agents do so directly; the nitrates come the closest. Such an agent would be useful because any therapeutic increase in aortic distensibility would decrease systolic pressure without greatly reducing diastolic pressure. The problem is complicated by the suspected inaccuracy of the cuff technique in predicting the aortic diastolic pressure. New noninvasive methods to predict the aortic diastolic pressure may help in the future. At present, the combination of a high systolic and normal diastolic pressure-a widened pulse pressure-seems to be the best predictor of cardiovascular risk in patients with hypertension or heart disease. Patients with isolated systolic hypertension should be treated, but marked diastolic hypotension should be avoided.
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PMID:The diastolic blood pressure in systolic hypertension. 1065 5

Endothelial nitric oxide synthase (eNOS), encoded by NOS3, is a potent regulator of vasomotor tone and peripheral resistance. Congenic experiments indicate that a chromosomal segment containing the rat eNOS gene contributes to rat spontaneous hypertension (HT). A role for NOS3 in onset of essential hypertension (HT) is, however, controversial. We therefore decided to test NOS3 polymorphisms in a set of patients who have an accentuated ability to show an existing genetic association. The 112 HT subjects had two HT parents and the normotensive (NT) subjects had two NT parents. All were Anglo-Celtic whites. The two most promising polymorphisms, viz, a biallelic variable number of tandem repeats (VNTR) in intron 4 and an exon 7 variant that leads to an amino acid change (Glu298Asp), were genotyped by PCR (and BanII digestion in the case of the latter). Frequency of the minor allele of the VNTR was 0.11 in the NT and 0.10 in the HT subjects (P = .9). For the exon 7 variant, Asp298 frequency was 0.30 and 0.32 in each respective group (P = .6). Tracking was seen for the Asp298 allele with elevation in body mass index (P = .034), and the minor allele of the VNTR with elevation in LDL (P = .007) and reduction in HDL (P = .048). In conclusion, we saw no association of NOS3 markers with HT in the population studied. However, possible genotypic effects on plasma lipids and body mass index might warrant further studies, especially in view of possible associations with heart disease.
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PMID:Association analyses of endothelial nitric oxide synthase gene polymorphisms in essential hypertension. 1098 49

Essential hypertension is an escalating problem for industrialized populations. It is currently seen as a 'complex' genetic trait caused by multiple susceptibility genes the effects of which are modulated by gene-environment and gene-gene interactions. Nevertheless, the success to date in identifying these susceptibility genes has been very limited. A number of candidates has been proposed, but demonstrating consistently the linkage or association with hypertension has been problematic. The data for angiotensinogen is undoubtedly the most extensive and meta-analysis has confirmed a significant association overall, although the risk contributed by this gene appears to be modest (odds ratio of 1.2). Identifying further genes - probably conferring even smaller attributable risks - represents a major challenge for future developments in this area. This contrasts markedly with the success that has been achieved in the past 5 years in solving the molecular genetics of a number of rare familial hypertension syndromes. The true incidences of some of these disorders may be higher than first appreciated, but it is still unclear if the genes for these syndromes also play a part in essential hypertension. A more complete understanding of the genetic basis of essential hypertension should be possible in the coming years using new strategies that take advantage of the information provided by the human genome project. This knowledge will irrevocably change the way we approach this disease in terms of its diagnosis, risk assessment for end-points such as stroke and heart disease, and the customised treatment that might be offered in the future.
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PMID:The genetics of essential hypertension. 1116 60

Regional sympathetic activity can be studied in humans using electrophysiological methods measuring sympathetic nerve firing rates and neurochemical techniques providing quantification of noradrenaline spillover to plasma from sympathetic nerves in individual organs. Essential hypertension: Such measurements in patients with essential hypertension disclose activation of the sympathetic outflows to skeletal muscle blood vessels, the heart and kidneys, particularly in younger patients. This sympathetic activation, in addition to underpinning the blood pressure elevation, most likely also contributes to left ventricular hypertrophy, and to the commonly associated metabolic abnormalities of insulin resistance and hyperlipidaemia. Antihypertensive drugs, such as moxonidine, which act primarily by inhibiting the sympathetic nervous system, should have additional clinical benefits beyond those attributable to blood pressure reduction, in protecting against hypertensive complications. Obesity-related hypertension: Understanding the neural pathophysiology of hypertension in the obese has been difficult. In normotensive obesity, renal sympathetic tone is doubled, but cardiac noradrenaline spillover (a measure of sympathetic activity in the heart) is only 50% of normal. In obesity-related hypertension, there is a comparable elevation of renal noradrenaline spillover, but without suppression of cardiac sympathetics (cardiac sympathetic activity being more than double that of normotensive obese and 25% higher than in healthy volunteers). Increased renal sympathetic activity in obesity may be a 'necessary' cause for the development of hypertension (and predisposes to hypertension development), but apparently is not a 'sufficient' cause. The discriminating feature of the obese who develop hypertension is the absence of the adaptive suppression of cardiac sympathetic tone seen in the normotensive obese. Heart failure: In cardiac failure, the sympathetic nerves of the heart are preferentially stimulated. Noradrenaline release from the failing heart at rest in untreated patients is increased as much as 50-fold, similar to the level seen in the healthy heart during near-maximal exercise. Activation of the cardiac sympathetic outflow provides adrenergic support to the failing myocardium, but at a cost of arrhythmia development and progressive myocardial deterioration. Psychosomatic heart disease: No more than 50% of clinical coronary heart disease is explicable in terms of classical cardiac risk factors. There is gathering evidence that psychological abnormalities, particularly depressive illness, anxiety states, including panic disorder and mental stress, are involved here, 'triggering' clinical cardiovascular events, and possibly also contributing to atherosclerosis development. The mechanisms of increased cardiac risk attributable to mental stress and psychiatric illness are not entirely clear, but activation of the sympathetic nervous system seems to be of prime importance.
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PMID:Sympathetic nervous system activation in essential hypertension, cardiac failure and psychosomatic heart disease. 1134 14

The pathogenesis and clinical significance of cerebral white matter lesions (WML) remain controversial. Most studies have shown that age, hypertension, diabetes mellitus, and a history of stroke or heart disease are the most important factors related to the presence of cerebral WML. Moreover, some studies suggest that the presence of WML are closely related to cerebrovascular disease and cognitive impairment in elderly patients with vascular risk factors, particularly hypertension. In this review, different points of view about cerebral WML are discussed, with special focus on the presence of WML in essential hypertension. Some authors suggest that the presence of WML in hypertensive patients could be considered an early marker of brain damage.
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PMID:Cerebral white matter lesions in essential hypertension. 1155 79


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