A rational approach to hypertension treatment in the older patient.
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Adrenergic beta-Antagonists↗
Biomedical subjects
J M Flack
Publications and source records attributed to J M Flack.
Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia.
Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver--key sites for cell and water homeostasis and lipoprotein regulation, respectively--may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Implications of obesity for cardiovascular disease in blacks: the CARDIA and ARIC studies.
To examine the relation of obesity to cardiovascular disease in blacks, we analyzed data from two population studies, including young and middle-aged adults. Obesity, defined by using the sum of subscapular and triceps skinfold measurements, was positively associated with atherogenic plasma lipids, systolic blood pressure, serum glucose and insulin, and prevalence of diabetes mellitus. The strength of these associations, for the most part, was similar in blacks and whites. However, with each unit increase in sum of skinfold thicknesses, plasma triglyceride concentrations in blacks appeared to increase only one-third to one-half as much as in whites. Prevalence of cardiovascular disease in 45- to 65-y-old blacks was associated with obesity; the odds ratio (95% confidence interval), adjusted for age and cigarette smoking, was 1.3 (0.9, 1.8) in both black men and black women. Additional analyses showed that abdominal adiposity conferred increased risk. These findings suggest that both blacks and whites should avoid excess adiposity.
Adolescent↗
Racial and ethnic modifiers of the salt-blood pressure response.
The relation between sodium and blood pressure is a centuries-old question. A substantial body of epidemiological and experimental data has accumulated that strongly implicates NaCl as having a causal role in the genesis of arterial hypertension. Prospective studies that have been performed in diverse populations that have manipulated NaCl exposure by diet or infusion have repeatedly documented an NaCl pressor effect. Further, similar studies in biracial populations have also demonstrated a greater prevalence of "salt sensitivity" in blacks compared with whites. The reasons for this observation are not entirely clear; however, intrinsic or hypertension-induced renal abnormalities that limit natriuretic capacity, reduced Na+,K(+)-ATPase pump activity, other membrane ion transport disturbances, differential exposure to psychological stressors, greater insulin resistance, and dietary factors (reduced Ca+ and K+ intake) have all been suggested as possibly playing a role. Salt sensitivity appears to be a widespread phenomenon. However, it is critically important to determine what factors account for racial differences in salt sensitivity. Moreover, the prevalence of salt sensitivity in the general population is unknown. Current definitions of salt sensitivity are varied and unidirectional. In comparison with bidirectional criteria (blood pressure increase with salt loading and blood pressure decrease with salt restriction), they are probably inadequate to identify salt-sensitive individuals who manifest less extreme blood pressure change after dietary sodium or plasma volume manipulations. More sensitive criteria for diagnosing salt sensitivity will facilitate a better understanding of racial and ethnic differences in the prevalence of salt sensitivity.
Black People↗
Epidemiology of hypertension and hypertensive target-organ damage in the United States.
Hypertension and hypertension-related cardiovascular renal sequelae remain major clinical and public health problems in the United States, particularly among African Americans. Compared with whites, African Americans have higher incidence and prevalence rates for hypertension; these differentials are more pronounced in young adult women. Among the very old, race differentials in hypertension prevalence rates are less pronounced. The reasons for the epidemic hypertension rates in the United States are largely environmental: obesity, physical inactivity, high salt and alcohol intake, and psychosocial stress have all been identified as causes. Obesity and physical inactivity probably account for a significant proportion of the premature excess hypertension in African Americans relative to white women. Putative genetic differences between African Americans and whites are unlikely to account for the differential in hypertension rates. During the last 20 years tremendous strides have been made in the identification, treatment, and control of hypertension in the African-American community. Yet, there is further progress to be made. Preventing hypertension precursor conditions (ie, obesity, excess salt intake, psychosocial stressors), normalizing blood pressure levels (less than 140/90 mm Hg), reducing the prevalence of severe hypertension (greater than 160/90 mm Hg), and linking psychosocial correlates of blood pressure to cardiovascular-renal physiology (ie, salt sensitivity) remain as major challenges for those involved in hypertension management and research in African-American communities.
Adolescent↗
Cardiovascular risk factor prevalence in African-American adult screenees for a church-based cholesterol education program: the Northeast Oklahoma City Cholesterol Education Program.
The status of selected cardiovascular risk factors was ascertained in a consecutive sample of 661 (222 men and 439 women) African-American adults who were screened for the Northeast Oklahoma City Cholesterol Education Program, a church-based cholesterol intervention program. Hypertension was present in 48.4% and 44.7% of men and women, respectively. Average systolic blood pressure levels were similar in men and women (132.0 vs 131.5 mm Hg, P = 0.40) although average diastolic blood pressure levels were higher in men (84.0 vs 81.1 mm Hg; P < .0001). A substantial proportion of the screenees were unaware of their hypertension, and blood pressure normalization (SBP < 140 and DBP < 90 mm Hg) was uncommon in drug-treated hypertensives. Average cholesterol levels were slightly higher in women compared to men (206.0 vs 199.6 mg/dL, P = 0.11). The majority of persons with elevated cholesterol levels (> or = 240 mg/dL) were unaware of their condition and were infrequently treated with cholesterol-lowering drugs. Overweight was highly prevalent, was more common with advancing age, and was related to the presence of hypertension in both men and women. In addition, a strong linear relation between overweight and blood pressure was present in both sexes. Overweight was more common in young men (< 35 years old) compared to age-matched women; however, women were increasingly more overweight than men after 35-44 years of age. In fact, by age 65, 90% of the women were overweight. These data indicate an excessive prevalence and high mean levels of modifiable cardiovascular risk factors in these church-attending African-American adults. Because churches are a central institution in most African-American communities, and their congregations appear to have an excessive cardiovascular disease risk factor burden, churches may be appropriate sites for the implementation of community-based risk factor control programs.
Adult↗
A micro-enzymatic method to measure cholesterol and triglyceride in lipoprotein subfractions separated by density gradient ultracentrifugation from 200 microliters of plasma or serum.
A micro-enzymatic method was developed to measure total cholesterol (CHOL) and triglyceride (TG) in lipoproteins and their subfractions separated by density gradient ultracentrifugation. This method had a detection limit and sensitivity below 2 mg/dl and accuracy (bias to reference sera) and imprecision (coefficient of variation) of less than 3% between 2 and 30 mg/dl for both CHOL and TG. In addition, the method was in good agreement with standardized Abell-Kendall CHOL (r = 0.98) and enzymatic TG (r = 0.99) methods. Lipoproteins from 200 microliters of plasma or serum were separated by either equilibrium (EQ)- or rate zonal (RZ)-density gradient ultracentrifugation and the resulting fractions were analyzed for CHOL and TG by the micro-enzymatic method. Lipoprotein measurements by these micro-enzymatic/density gradient methods were highly correlated with standardized Lipid Research Clinic (LRC) procedures and preparative ultracentrifugation. The EQ-density gradient procedure also allowed determination of CHOL and TG in LDL and HDL subfractions within any desired density interval. These methods will facilitate the measurements and study of lipoproteins and their subfractions especially in infants, children, the elderly, and small animals. In addition, the micro-enzymatic method may be adapted to other modes of lipoprotein separation such as liquid chromatography, electrophoresis, and precipitation. CHOL or TG determinations could be made on approximately 500 density gradient fractions per hour.
Adult↗
A comparison of antihypertensive drug effects on the progression of extracranial carotid atherosclerosis. The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS).
Hypertension is a major risk factor for coronary heart disease (CHD) and is the primary risk factor for stroke. Drug trials lowering blood pressure by pharmacological means have demonstrated impressive reduction in both fatal and nonfatal stroke (33 to 50%) that are virtually identical to the predicted stroke reduction, considering the observed diastolic blood pressure change (5 to 6mm Hg). On the other hand, reduction of CHD risk has been less impressive in these same trials. Although statistically significant, the reduction in CHD risk is roughly one-half (14%) of that predicted (25%) when results from these drug trials are analysed in aggregate. Most trials have used moderate to high dosages of thiazide diuretics or beta-blockers as therapies. Several factors may account for the disappointing results in CHD risk reduction. These drugs may induce metabolic disturbances in lipids, increased glucose tolerance, insulin resistance, or cause inadequate regression of left ventricular hypertrophy, thus attenuating the predicted reduction in CHD risk associated with pharmacological blood pressure lowering. Isradipine is a new dihydropyridine calcium antagonist that is highly effective in lowering blood pressure. Isradipine also has antiatherogenic properties in animal models of atherosclerosis. The effect of isradipine on atherosclerosis in humans is unknown. The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) is a 3-year double-blind, randomised trial in over 800 men and women with hypertension, aged 40 years or older. The primary aim of MIDAS is to compare the efficacy of isradipine 2.5 to 5.0mg twice daily vs hydrochlorothiazide 12.5 to 25mg twice daily in retarding the progression of extracranial carotid atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Management of hypertension. Potential trade-offs on coronary risk.
The major risk factors for coronary heart disease remain high blood pressure, cigarette smoking, and abnormal serum lipid levels, including total cholesterol but more specifically elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol levels. Observations made from large-scale trials almost a decade ago suggested that commonly used antihypertensive agents, such as thiazide diuretics and beta-blockers, may adversely influence serum lipid levels. Over time, we realized that these lipid alterations persist long term and are of sufficient magnitude to potentially account for important differences in coronary heart disease risk reduction among various antihypertensive drug regimens. Considering recent National Cholesterol Education Program and Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommendations concerning lipid and blood pressure treatment, it is prudent and timely to rethink our approach to antihypertensive therapy in patients with abnormal serum lipid levels. Therefore, when lipids are a concern, appropriate dietary treatments should be advised and antihypertensive therapy that has a beneficial or neutral impact on serum lipid levels should be considered.
Antihypertensive Agents↗
Long-term effects on plasma lipids of diet and drugs to treat hypertension. Treatment of Mild Hypertension Study (TOMHS) Research Group.
OBJECTIVE: - To compare long-term plasma lipid changes among 6 antihypertensive treatment interventions for stage I (mild) hypertension. DESIGN: - Multicenter, randomized, double-blind, parallel-group clinical trial. SETTING: - Four academic clinical research units in the United States. PARTICIPANTS: - A total of 902 men and women, aged 45 to 69 years, with stage I diastolic hypertension (diastolic blood pressure <100 mm Hg), recruited from 11914 persons screened in their communities. INTERVENTIONS: - Participants were randomized to 1 of 6 treatment groups: (1) placebo, (2) beta-blocker (acebutolol), (3) calcium antagonist (amlodipine), (4) diuretic (chlorthalidone), (5) alpha1-antagonist (doxazosin), and (6) angiotensin-converting enzyme inhibitor (enalapril). All groups received intensive lifestyle counseling to achieve weight loss, dietary sodium and alcohol reduction, and increased physical activity. MAIN OUTCOME MEASURES: - Changes in plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides from baseline to annual visits through 4 years. RESULTS: - Mean changes in all plasma lipids were favorable in all groups. The degree of weight loss with fat-modified diet and exercise was significantly related to favorable lipid changes. Significant differences (P<.01) among groups for average changes during follow-up in each lipid were observed. Decreases in plasma total cholesterol and LDL cholesterol were greater with doxazosin and acebutolol (for plasma total cholesterol, 0.36 and 0.30 mmol/L [13.8 and 11.7 mg/dL], respectively), less with chlorthalidone and placebo (0.12 and 0.13 mmol/L [4.5 and 5.1 mg/dL], respectively). Decreases in triglycerides were greater with doxazosin and enalapril, least with acebutolol. Increases in HDL cholesterol were greater with enalapril and doxazosin, least with acebutolol. Significant relative increases in plasma total cholesterol with chlorthalidone compared with placebo at 12 months were no longer present at 24 months and beyond, when mean plasma total cholesterol for the chlorthalidone group fell below baseline. Analyses of participants continuing to receive chlorthalidone throughout the 4 years of follow-up indicated this was not due solely to an increasing percentage of participants changing or discontinuing use of medication during follow-up. CONCLUSIONS: - Weight loss with a fat-modified diet plus increased exercise produces favorable long-term effects on blood pressure and all plasma lipid fractions of adults with stage I hypertension; blood pressure reduction is enhanced to a similar degree by addition of a drug from any one of 5 classes of antihypertensive medication. These drugs differ quantitatively in influencing the degree of long-term favorable effects on blood lipids obtained with nutritional-hygienic treatment.
Acebutolol↗
Coronary heart disease in African Americans.
African Americans have the highest overall mortality rate from coronary heart disease (CHD) of any ethnic group in the United States, particularly out-of-hospital deaths, and especially at younger ages. Although all of the reasons for the excess CHD mortality among African Americans have not been elucidated, it is clear that there is a high prevalence of certain coronary risk factors, delay in the recognition and treatment of high-risk individuals, and limited access to cardiovascular care. The clinical spectrum of acute and chronic CHD in African Americans is similar to that in whites. However, African Americans have a higher risk of sudden cardiac death and present more often with unstable angina and non-Q-wave myocardial infarction than whites. African Americans have less obstructive coronary artery disease on angiography, but may have a similar or greater total burden of coronary atherosclerosis. Ethnic differences in the clinical manifestations of CHD may be explained largely by the inherent heterogeneity of the coronary syndromes, and the disproportionately high prevalence and severity of hypertension and type 2 diabetes in African Americans. Identification of high-risk individuals for vigorous risk factor modification-especially control of hypertension, regression of left ventricular hypertrophy, control of diabetes, treatment of dyslipidemia, and smoking cessation--is key for successful risk reduction.
Age Factors↗
A church-based cholesterol education program.
The leading cause of death among black people in the United States is coronary heart disease, accounting for about 25 percent of the deaths. The Task Force on Black and Minority Health formed by the Secretary of Health and Human Services in 1985 subsequently recommended increased efforts to reduce risk factors for coronary heart disease in the black population. A stated focus of the National Heart, Lung, and Blood Institute's National Cholesterol Education Program has been that of reaching minority groups. This report describes a pilot cholesterol education program conducted in black churches by trained members of those churches. Cholesterol screening, using a Reflotron, and other coronary heart disease risk factor screening was conducted in six churches with predominantly black members and at a neighborhood library. A total of 348 persons with cholesterol levels of 200 milligrams per deciliter (mg per dl) or higher were identified. At the time of screening, all were provided brief counseling on lowering their cholesterol and were given a copy of the screening results. Half of those identified, all members of one church, were invited to attend a 6-week nutrition education class of 1 hour each week about techniques to lower blood cholesterol. Information about cholesterol was also mailed to them. They were designated as the education group. Persons in the church were trained to teach the classes. A report of the screening results was sent to the personal physicians of the remaining 174 people in other churches who had cholesterol levels of 200 mg per dl or higher. This group served as a usual care comparison group.Six months after the initial screening, members of both groups were invited for followup screening.Among the 75 percent of the education group who returned for followup screening there was a 23.4 mg per dl (10 percent) decrease in the mean cholesterol level. Thirty-six percent of the usual care group returned for followup screening; their mean cholesterol level had decreased 38.7 mg per dl (16 percent).In this study, the support of churches provided access to large numbers of people. The mean serum cholesterol reductions occurring with both screening and referral and screening and education were statistically significant and large enough to be of clinical importance.The authors recommend that the approach taken in this study be investigated further by the National Cholesterol Education Program as a model for reaching the black population with coronary heart disease risk reduction programs.
Adult↗
High blood pressure in older persons: a high risk special population.
Blood pressure (BP), particularly systolic blood pressure (SBP), rises with advancing age. Isolated systolic hypertension is the most common type of hypertension (HTN) phenotype after age 70. Moreover, at similar BP levels the absolute risk for CVD is several fold higher in elderly than in young patients. End-organ damage is common, and significant renal impairment can be present even when serum creatinine levels are normal. All forms of HTN in the elderly should be treated. A recent meta-analysis of eight clinical trials involving elderly patients documented a 15/6 mm Hg treatment difference between intervention and control groups, and a lower rate of stroke, CHD and death from all causes in the intervention group. Gradual BP control into the "normal" range should be the goal in elderly patients. There is no convincing evidence that lowering BP is harmful (J-curve hypothesis). Coexisting medical conditions influence therapeutic choices. The suggested medical evaluation of elderly hypertensive patients with suspected secondary forms of HTN is covered as well as pervasive clinical myths about HTN in the elderly.
Age Factors↗
Living with hypertension. Introduction to dealing with elevated blood pressure.
Gaining control of hypertension requires a large effort on the part of not only the patient and physician, but other health care providers as well. Successful hypertension management is defined as lowering blood pressure to less than 140 millimeters of mercury systolic and less than 90 millimeters of mercury diastolic. If blood pressure is lowered gradually, one can expect to feel better. In most situations, there is no benefit in rapidly lowering blood pressure. The down side of rapid blood pressure lowering is that individuals tend to feel bad, at least temporarily, and are likely to discontinue medication. Patience is the key. It takes at least four to six weeks to achieve normal blood pressure when a new medication is started. Almost all of the blood-pressure medications work better when the individual makes lifestyle changes (loses weight, reduces salt and alcohol intake, and increases aerobic activity).
Humans↗