Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review discusses the genetic factors in the development of arteriosclerosis and coronary heart disease (CHD). In several studies, multivariate analysis of prospective mortality/morbidity data and angiographic findings have indicated that a family history of CHD contributed to CHD risk independently of the established risk factors. In addition, ethnic groups that differ in the prevalence and incidence of CHD also markedly differ in blood groups and protein-enzymatic markers. These or other genetic differences may affect CHD rates. Data from fraternal and identical twins, the source of some early genetic CHD findings, are reviewed. Genetic disorders of lipoprotein metabolism and transport, such as familial hypercholesterolemia, as well as other monogenic disorders are discussed. The role of apoprotein E polymorphism i other monogenic disorders are discussed. The role of apoprotein E polymorphism in determining plasma LDL variability among individuals is considered. Recombinant DNA technology, molecular cloning, and the identification of restriction fragment length polymorphisms are new tools for investigators who assess DNA polymorphism. Recent advances in that domain include: DNA polymorphisms affecting blood levels of apo A-I and A-II, association of a DNA insertion on chromosome 19 with severe premature atherosclerosis, and information concerning linkage of the genes for various apolipoproteins. In addition, the evidence for a major genetic component in diabetes mellitus and research into the genetic aspects of hypertension are reviewed. The male/female ratio in pathologically and epidemiologically assessed atherosclerosis may provide clues to the role of genetics. Early structural changes in the coronary artery intima are compatible with the ethnic and gender predilection. A key question in understanding underlying mechanisms in atherosclerosis is why coronary arteries are occluded in individuals whose other arterial systems are largely unaffected. The review concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on uncovering genetically determined differences in arterial wall response to blood flow. Subpopulations with different genetic risks may be identified, in which case universal preventive strategies might be replaced with specific ones.
 ...
PMID:Genetic aspects of arteriosclerosis. 352 20

The LA/N rat is one of two congenic strains bred from the original obese, hyperphagic and hypertensive rats of Koletsky. With the exception of hypertension the LA/N strain, when homozygous for the corpulent gene, is phenotypically similar to the parent Koletsky strain and prone to the development of vascular and myocardial lesions. Here we report a detailed analysis of the serum lipids, lipoproteins and apolipoproteins B, E and A-I levels in young adult homozygous corpulent (cp/cp) rats of both sexes and in lean males of the same age which were demonstrable non-carriers (+/+) of the cp gene. Both male and female cp/cp rats were hypertriglyceridemic (282-512 mg/100 ml) and moderately hypercholesterolemic (74-84 mg/100 ml). Elevations in these lipids reflected the presence of large (622 A), triacylglycerol-rich and apoprotein-poor VLDL containing both apolipoproteins Bh and B1 and increased phospholipid-rich HDL. Similar, but less pronounced, elevations in serum apolipoproteins B and E in the cp/cp rats when compared to the +/+ animals were also noted. Apolipoproteins A-I levels were 2.7-3-fold higher in cp/cp rats. The levels of VLDL were significantly higher in female cp/cp rats; however, the levels of IDL (intermediate-density lipoproteins), LDL and HDL were significantly lower than in the more atherosclerosis prone male cp/cp rats. Similarly, apolipoprotein A-I was higher and apolipoprotein B lower in the male cp/cp than in the female cp/cp rats. The LDL (d = 1.030-1.063 g/ml) in cp/cp rats, like that in normal animals, was heterogeneous and contained apolipoproteins Bh, E, A-I and C. This fraction was significantly elevated in male cp/cp rats when compared to females but still represented less than 13% of the total serum cholesterol and less than 6% of the total serum lipids in 3-month-old cp/cp animals. The ratio of cholesterol to phospholipids was significantly lower for all lipoproteins in cp/cp rats when compared to +/+ males and these ratios for female cp/cp rats were in all cases lower than those of male cp/cp animals.
 ...
PMID:Serum lipids and lipoproteins in the atherosclerosis prone LA/N corpulent rat. 358 Mar 82

In order to investigate comparatively the effects of prazosin and atenolol on plasma lipid concentrations, 60 patients from two centres, presenting with arterial hypertension (diastolic 90-120 mmHg, systolic 160-200 mmHg), were allocated at random to one or the other of these drugs. The lipid profile, stable during the period of observation, included total cholesterol and triglycerides, study by ultracentrifugation, and assays of apoproteins A1 and B by laser immunonephelometry. Determinations were performed 30 days before, and on the 1st, 90 th and 180 th days of treatment. Both drugs had similar lowering effects on blood pressure. A significant decrease in total cholesterol, LDL cholesterol and apoprotein B and an increase in HDL cholesterol and apolipoprotein A1 were observed in patients under prazosin, whereas patients under atenolol exhibited opposite variations in plasma lipids. Although the clinical significance of these findings is uncertain, such metabolic effects should be taken into account when evaluating the risk/benefit ratio of antihypertensive treatments.
 ...
PMID:[Comparative study of the effects of prazosin and atenolol on plasma lipids of hypertensive patients]. 389 49

Considering the documented, potentially undesirable influence of various thiazide-type or loop diuretics on serum lipoproteins, we prospectively investigated in 69 men (mean age +/- SEM, 32 +/- 1 years) the metabolic effects of the new diuretic-antihypertensive compound indapamide. Compared to placebo, indapamide (2.5 mg/day) given for 6 to 8 weeks lowered (p less than 0.02 to less than 0.001) blood pressure (supine values from 148/98 +/- 3/2 to 137/93 +/- 3/2) in 29 men with mild to moderate essential hypertension, but not in 40 healthy men. In both groups, significant (p less than 0.05 to less than 0.001) decreases in body weight (-0.8 kg) and plasma potassium (-0.6 mmol/L), and increases in plasma uric acid (+20%), renin activity (+200%), and aldosterone documented good compliance. There were no significant changes in total cholesterol (in all subjects, from 208 +/- 6 to 213 +/- 6 mg/dl), low- or very low-density lipoprotein (VLDL) cholesterol (127 +/- 6 to 129 +/- 6 and 21 +/- 1 to 21 +/- 2 respectively), high-density lipoprotein cholesterol (50 +/- 1 to 51 +/- 1 mg/dl), total triglycerides (Tg) (108 +/- 5 to 112 +/- 6 mg/dl), VLDL-Tg, apoproteins A1 and A2, plasma glucose, epinephrine, norepinephrine, sodium, calcium, magnesium, and creatinine; apoprotein B (84 +/- 2 to 88 +/- 3 mg/dl) and plasma insulin after glucose loading dose tended to be increased minimally. The absence of distinct lipoprotein alterations after short-term indapamide treatment may be of clinical and epidemiological interest.
Hypertension
PMID:Serum lipoproteins during treatment with the antihypertensive agent indapamide. 407 35

It is certain that atherosclerosis is multi-factorial. Amongst the numerous risk factors two are particularly important: hypertension and primary or secondary abnormalities of plasma lipids and lipoproteins (high levels of total cholesterol, LDL and VLDL cholesterol, triglycerides or VLDL triglycerides, apoprotein B, low levels of HDL cholesterol, apoprotein A1 and probably HDL2). On the basis of a general review of the literature, the authors evaluate the changes in lipids, lipoproteins and apoproteins induced by different beta-blockers. Overall, the most constant and most obvious (particularly in hyperlipidaemic patients) disturbances combine an increase in total triglycerides or VLDL triglycerides and a fall in HDL cholesterol. There is little change in total cholesterol or LDL cholesterol. Side effects seen with most beta-blockers, cardioselective or not, differ in degree from one drug to another. They are particularly marked with some (propranolol) while they are virtually absent with others (pindolol). The mechanism of action is discussed (essentially inhibition of extra-hepatic lipoprotein lipase activity). These findings would seem to lead to the following practical conclusions: 1) Before starting antihypertensive treatment it is important to confirm lipid and lipoprotein levels, particularly bearing in mind the epidemiological links between moderate essential hypertension and lipoprotein abnormalities, especially those with a component of hypertriglyceridaemia. 2) Lipid profile including estimation by precipitation of HDL cholesterol must be studied during antihypertensive therapy and if there is a marked and confirmed deterioration towards an "increased atherogenicity", it is reasonable to envision a change of the antihypertensive agent. With the some efficacy on blood pressure levels and general tolerance, the choice should favour drugs having the least unfavourable effects on lipoprotein metabolism.
 ...
PMID:[Changes in lipids and lipoproteins caused by the beta-blocking agents used as antihypertensives]. 613 67

The effects of propranolol and prazosin on plasma lipoproteins in patients with essential hypertension were evaluated according to a crossover protocol of two 8-week periods with a washout of 4 to 6 weeks. Eleven patients with moderate hypertension (greater than 90 but less than or equal to 144 mm Hg, diastolic) and slightly overweight (+10% to +/- +30%, according to Metropolitan Life Insurance tables) were selected. No dietary changes were prescribed. Plasma cholesterol, triglycerides (TG), and lipoprotein changes were monitored at the beginning of each sequence and at 2-, 4- and 8-week intervals. Prazosin, when given first, did not essentially modify any of the metabolic parameters, except for a slight elevation in plasma apoprotein AI levels, i.e., the main protein component of high density lipoprotein (HDL); propranolol caused a significant rise in total TG and very low density lipoprotein TG (VLDL-TG) levels (+37.3% and +23.9%, respectively). Somewhat lower total TG (+19.6%) and vLDL (17.8%) TG elevations were noted when propranolol was given first; plasma glucose was also significantly raised (+12.8%). Triglyceride and glucose levels returned to normal upon changing to prazosin. Total plasma- and lipoprotein-associated cholesterol levels were essentially unchanged with either drug; similarly, no significant changes were detected in total plasma apoprotein B (the main protein component of LDL and also VLDL), a component of apoprotein AI levels. Uric acid levels were slightly raised on propranolol. There was an 8.8% reduction in uric acid levels when the medication changed from propranolol to prazosin.
 ...
PMID:Plasma lipid and lipoprotein changes in hypertensive patients treated with propranolol and prazosin. 617 63

We examined 82 patients 10 years after saphenous-vein aortocoronary bypass surgery to determine their angiographic status and to relate those findings to the risk factors for coronary-artery disease. Of 132 grafts shown to be patent 1 year after surgery, only 50 were unaffected at 10 years. The remainder were narrowed (43) or occluded (39). Disease progression in coronary arteries without grafts was also frequent, both in vessels that were normal (15 of 32) and in those with minor stenosis (25 of 53). New lesions did not develop in 15 patients, whereas they did in 67--in the grafts, the native vessels, or both. There was no significant difference between the two groups in the incidence of hypertension, diabetes, or smoking, whereas plasma levels of very-low-density lipoproteins (VLDLs) and low-density lipoproteins (LDLs) were higher, and high-density lipoprotein (HDL) levels were lower in those with new disease than in those without. Univariate analysis showed that plasma cholesterol and triglyceride levels were significantly higher at the time of surgery and at the 10-year examination in those with new lesions. Multivariate analysis indicated that among the lipoprotein indexes, levels of HDL cholesterol and plasma LDL apoprotein B best distinguished the two groups. The findings indicate that atherosclerosis in these patients was a progressive disease, frequently affecting both the grafts and the native vessels, and that the course of such disease may be related to the plasma lipoprotein levels.
 ...
PMID:The relation of risk factors to the development of atherosclerosis in saphenous-vein bypass grafts and the progression of disease in the native circulation. A study 10 years after aortocoronary bypass surgery. 633 35

Patients with renal functional impairment are prone to develop hypertension and hyperlipidemia, and both abnormalities tend to occur already at an early stage of kidney disease. In 18 patients with mild renal disease (glomerular filtration rate 65 +/- 5 ml/min) and hypertension (mean blood pressure 126 +/- 4 mm Hg), the effect of six weeks of treatment with the loop-diuretic muzolimine on serum lipoproteins was assessed. Compared to placebo values, the diuretic significantly increased serum low-density lipoprotein cholesterol (LDL-C) and apoprotein B (+ 18 and 11%, respectively, P less than 0.005) in 13 men or postmenopausal women, but not in 5 premenopausal women. Serum high-density lipoprotein cholesterol (HDL-C), and total triglycerides or lipoprotein triglyceride fractions were not consistently changed in both subgroups. Thus, the ratio LDL-C/HDL-C was increased from 3.2 +/- 0.3 to 3.9 +/- 0.3 (P less than 0.05) in the men or postmenopausal women, while no such tendency occurred in the premenopausal women (4.1 +/- 0.6 to 3.7 +/- 0.6). Changes in serum LDL-C were not associated with hemoconcentration or alterations in carbohydrate metabolism and were not related to variations in serum potassium or blood pressure. Increased serum levels of the atherogenic LDL-C fraction during diuretic treatment in men or postmenopausal women with renal disease may represent a potentially undesirable effect, particularly since such patients may tend to have hyperlipidemia in the untreated state.
 ...
PMID:Serum lipoproteins in patients with mild renal disease treated with the diuretic muzolimine. 715 18

A multi-institutional study 'Pathobiological Determinants of Atherosclerosis in Youth' (PDAY) was initiated to document the natural history of atherosclerosis, its relationship to risk factors, and pathobiology of lesion development in young subjects. Pathology laboratories in nine centers collected arteries and tissues from over 2000 persons from 15 through 34 years of age whose deaths were attributed to homicides, accidents, or suicides. Arteries were evaluated for lesions, and risk factors were analyzed in a central laboratory. Post-mortem risk factors included serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes), thickness of panniculus adiposus (obesity), small renal artery changes (hypertension) and apoprotein isoforms. This study documents the development of atherosclerosis at an early age. It also shows that the recognized risk factors for coronary heart disease are associated with lesion development in the arteries of these young subjects. The PDAY study has a counterpart in Japan where the development of atherosclerosis has been studied in young subjects. This Japanese study, in a population in which coronary heart disease has not yet become a major epidemic, has findings quite similar to the findings from the PDAY study. Studies of atherosclerosis in both Japan and the USA provide strong justification for reducing risk factors in young persons.
 ...
PMID:Environmental and genetic risk factors in early human atherogenesis: lessons from the PDAY study. Pathobiological Determinants of Atherosclerosis in Youth. 758 30

A multi-institutional study, Pathobiological Determinants of Atherosclerosis in Youth (PDAY), was initiated to document the natural history of atherosclerosis, its relationship to risk factors, and the pathobiology of lesion development in young subjects. Pathology laboratories in nine centers collected arteries and tissues from > 2000 persons, ages 15-34 years, whose deaths were attributed to homicides, accidents, or suicides. Arteries were evaluated for lesions, and risk factors were analyzed in a central laboratory. Postmortem risk factors include serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes), thickness of panniculus adiposus (obesity), changes in small renal arteries (hypertension), and apoprotein isoforms. This PDAY study documents the development of atherosclerosis at an early age and shows that the recognized risk factors for coronary heart disease are associated with lesion development in the arteries of these young subjects. The findings provide a strong justification for reducing risk factors in young persons.
 ...
PMID:Natural history and risk factors for early human atherogenesis. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. 781 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>