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Biomedical subjects

S M Haffner

Publications and source records attributed to S M Haffner.

304 records · Page 17Linked to original sources

Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study.

BACKGROUND: Patients with diabetes mellitus (DM) have a marked increase in coronary heart disease (CHD) events relative to those without DM. In a previous report from the Scandinavian Simvastatin Survival Study using a clinical case definition of DM (n = 202), simvastatin-treated patients had significantly fewer CHD events compared with placebo-treated control subjects. OBJECTIVE: To examine the effect of simvastatin therapy on CHD in patients with DM and impaired fasting glucose levels. METHODS: Using the 1997 American Diabetes Association diagnostic criteria, we assessed the effect of simvastatin therapy post hoc for an average of 5.4 years in Scandinavian Simvastatin Survival Study patients with normal fasting glucose (n = 3237), impaired fasting glucose (n = 678), and DM (n = 483). RESULTS: Simvastatin-treated patients with DM had significantly reduced numbers of major coronary events (relative risk [RR] = 0.58; P = .001) and revascularizations (RR = 0.52; P = .005). Total (RR = 0.79; P = .34) and coronary (RR = 0.72; P = .26) mortality were also reduced in DM, but not significantly, due to small sample size. In impaired fasting glucose (IFG) subjects, simvastatin use significantly reduced the number of major coronary events (RR = 0.62; P = .003), revascularizations (RR = 0.57; P = .009), and total (RR = 0.57; P = .02) and coronary (RR = 0.45; P = .007) mortality. CONCLUSION: Our results extend previous findings in patients with DM to a larger cohort, confirming the benefit of cholesterol lowering with simvastatin treatment on CHD events. In addition, significant decreases in total mortality, major coronary events, and revascularizations were observed in simvastatin-treated patients with impaired fasting glucose levels. These results strongly support the concept that cholesterol lowering with simvastatin therapy improves the prognosis of patients with elevated fasting glucose levels (> or =6.0 mmol/L [> or =110 mg/ dL]) or DM and known CHD.

Anticholesteremic Agents↗

Detection and treatment of hypercholesterolemia in a biethnic community, 1979-1985.

Although hypercholesterolemia has been recognized as a risk factor for coronary heart disease (CHD) for decades, only in recent years have clinical trials definitively shown the efficacy of lowering serum cholesterol to prevent the occurrence or worsening of CHD. In 1985, an NIH consensus conference published guidelines for the diagnosis and treatment of hypercholesterolemia. Prior to 1985, physicians and lay people alike were not yet convinced of the necessity to know one's cholesterol level, nor did they know what levels should be treated. In a community-based survey of cardiovascular risk factors, known as the San Antonio Heart Study, in which 1,932 Mexican-Americans (MAs) and 1,133 non-Hispanic whites (NHWs) were examined between 1979 and 1985, the authors found that only 36/501 MAs (7%) and 54/312 NHWs (17%) in the moderate- or high-risk categories were aware that their cholesterols were high. Of the total number aware, including those whose cholesterol levels were in the low-risk range, only 23/97 MAs (24%) and 29/108 NHWs (27%) were receiving dietary or drug treatment. Of those being treated, only 9/23 MAs (39%) and 12/29 NHWs (41%) were effectively controlled. Mexican-Americans were less likely to be aware of their hypercholesterolemia than non-Hispanic whites, but both ethnic groups had low levels of treatment.

Adult↗

Diabetes and coronary heart disease risk in Mexican Americans.

Mexican Americans have a high prevalence of diabetes relative to non-Hispanic whites, but paradoxically experience a lower prevalence of myocardial infarction and lower cardiovascular mortality (at least in men). To determine whether Mexican Americans might be more resistant to the atherogenic effects of diabetes than non-Hispanic whites, we examined the associations between diabetes and myocardial infarction and selected coronary heart disease (CHD) risk factors in these two ethnic groups. The study population consisted of 5149 Mexican Americans and non-Hispanic whites who were 25 to 64 years old and recruited from the San Antonio Heart Study, a population-based study of cardiovascular risk factors and diabetes conducted between 1979 and 1988. Diabetic men were more than twice as likely to have an electrocardiography (ECG)-documented myocardial infarction than were nondiabetic men, while diabetic women were more than three times as likely to have a myocardial infarction than were nondiabetic women. In both sexes the association between myocardial infarction and diabetes was nearly identical between the two ethnic groups. In both ethnic groups diabetes was also more strongly associated with conventional CHD risk factors (e.g., triglycerides, systolic blood pressure, and high-density-lipoprotein cholesterol) in women than in men. Furthermore, these associations were at least as strong, if not stronger, in Mexican Americans as in non-Hispanic whites. Thus, these data provide no evidence to suggest that Mexican Americans are resistant to the lipid-altering effects of diabetes. We conclude that the protective effect against CHD conferred by Mexican American ethnicity may be obscured in part by the high prevalence of diabetes in this ethnic group.

Adult↗

The prediabetic problem: development of non-insulin-dependent diabetes mellitus and related abnormalities.

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with approximately two fold increase in coronary heart disease (CHD) in men and fourfold increase in CHD in women. In most studies, the duration of diabetes and severity of glycemia are only weakly related to CHD in NIDDM, suggesting that the prediabetic period may be important for the increased CHD in NIDDM subjects. Both hyperinsulinemia and/or insulin resistance predict the development of NIDDM. A number of studies have shown that increased cardiovascular risk factors (especially high triglyceride, blood pressure, and small dense low-density lipoprotein (LDL) and low high-density liproprotein (HDL) cholesterol) precede the onset of NIDDM. Recent data from the San Antonio Heart Study suggest that the atherogenic pattern of cardiovascular risk factors is more marked in prediabetic women than in prediabetic men, thus partially explaining the higher risk of CHD in prediabetic women than in prediabetic men. The atherogenic changes in cardiovascular risk factors appear to be mainly due to increased hyperinsulinemia and insulin resistance in nondiabetic subjects. Interventions to reduce cardiovascular disease in NIDDM subjects should emphasize the primary prevention of NIDDM and very aggressive treatment of traditional cardiovascular risk factors in prediabetic subjects. Treatment of hypertension and dyslipidemia in high-risk patients for NIDDM should avoid agents that further worsen insulin resistance (nicotinic acid, beta blockers, and thiazides), as subjects with hypertension and dyslipidemia are already at increased risk of NIDDM.

Cardiovascular Diseases↗

Quantitative genetics of dehydroepiandrosterone sulfate and its relation to possible cardiovascular disease risk factors in Mexican Americans.

Dehydroepiandrosterone sulfate (DHEAS) is an adrenal steroid which has been inversely associated with development of atherosclerosis. We estimated heritability of serum DHEAS levels in 564 related Mexican Americans. We found a significant heritability for DHEAS (h2 = 0.39, p < 0.001). Measures of alcohol consumption, reproductive status, body composition, and HDL3 levels showed significant relationships with serum DHEAS levels. Sex and age were significantly associated with the mean, but not the genetic variance, of DHEAS levels. The results of this study demonstrate a significant genetic influence on steroid concentration and help to quantify the factors contributing to cardiovascular disease risk in Mexican Americans.

Adolescent↗

Microalbuminuria. Potential marker for increased cardiovascular risk factors in nondiabetic subjects?

Microalbuminuria is associated with progression to renal disease in insulin-dependent diabetes and with increased mortality in noninsulin-dependent diabetes. In contrast, few studies have addressed the effect of microalbuminuria on cardiovascular risk in nondiabetics. We, therefore, determined the level of microalbuminuria in 316 nondiabetic subjects from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular risk factors. Microalbuminuria (greater than or equal to 30 mg/l) was found in 42 of these 316 subjects (13%). Subjects with microalbuminuria had significantly higher blood pressure, triglyceride concentration, sum of insulin concentrations during a glucose tolerance test, and prevalence of hypertension and of self-reported myocardial infarction than subjects without microalbuminuria. When subjects with hypertension were excluded (n = 27), normotensive subjects with microalbuminuria (n = 31) still had significantly higher triglyceride concentrations and insulin sum than normotensive subjects without microalbuminuria (n = 258), suggesting that an increased atherogenic risk factor pattern exists even in normotensive subjects with microalbuminuria. Microalbuminuria may be a marker for cardiovascular risk, although it is not certain whether microalbuminuria causes these metabolic changes or results from some metabolic disturbance such as insulin resistance.

Adult↗

Epidemiological correlates of high density lipoprotein subfractions, apolipoproteins A-I, A-II, and D, and lecithin cholesterol acyltransferase. Effects of smoking, alcohol, and adiposity.

Recent data suggest that the protection against ischemic heart disease afforded by high density lipoprotein (HDL) cholesterol (C) may be concentrated in the HDL2 subfraction. To examine the behavioral correlates of the HDL subfractions, we recalled 33 men and 17 women of a random sample from the Pacific Northwest Bell Telephone Company Health Survey. Adiposity and very low density lipoprotein (VLDL) triglyceride were negatively correlated with HDL2C. Smoking was not correlated with HDL2C, but was negatively correlated with HDL3C (men, rs = -0.635, p = 0.001; women, rs = -0.534, p = 0.014); this relationship was independent of alcohol consumption, adiposity, and VLDL triglyceride. Alcohol consumption was also more strongly related to HDL3C (men, rs = 0.248, p = 0.082; women, rs = 0.586, p = 0.007). Lecithin cholesterol acyltransferase (LCAT) mass was negatively related with HDL2C, but was positively correlated with HDL3C and apolipoprotein A-II. Smoking was negatively correlated with LCAT mass. Since it is believed that HDL3C is not associated with the risk of ischemic heart disease and since both smoking and alcohol consumption may mainly affect HDL3C, the current study suggests that the increase in risk of ischemic heart disease with smoking and the possible decrease with alcohol consumption may be mediated through mechanisms other than their effects on HDLC.

Adult↗

Postheparin plasma triglyceride lipases. Relationships with very low density lipoprotein triglyceride and high density lipoprotein2 cholesterol.

Hepatic triglyceride (HTGL) and lipoprotein lipase (LPL) probably have major roles in the removal of triglyceride from triglyceride-rich lipoprotein and in the formation of high density lipoprotein (HDL). However, no population-based study of their activity and relationship to lipoprotein lipid levels has been reported. To determine these relationships, we recalled 33 men and 17 women of a randomly selected sample of the Lipid Research Clinics Pacific Northwest Bell Telephone Company Health Survey. The subjects were 53 +/- 7 years old (mean +/- SD) with total triglyceride levels of 120 +/- 57 mg/dl and total cholesterol levels of 224 +/- 35 mg/dl. Postheparin plasma LPL activity (127 +/- 61 nmol/min/ml) was not significantly correlated with either age, sex, or adiposity. In contrast, HTGL activity was significantly higher in men (235 +/- 84 nmol/min/ml) than women (170 +/- 91 nmol/min/ml, p less than 0.02), and was correlated with age in men and with adiposity in women. In both men and women, HTGL activity was related positively with VLDL triglyceride and inversely with HDL2 cholesterol. When the association between HTGL activity and VLDL triglyceride was examined with values from men and women pooled, the relationship was not weakened after adjustment for the linear effect of sex, adiposity, LPL, or HDL2 cholesterol.

Adult↗

Body fat distribution and hyperinsulinemia as risk factors for diabetes and cardiovascular disease.

Differences in body fat distribution between diabetics and nondiabetics have been recognized for several decades; diabetics have a more centralized or upper body fat pattern than nondiabetics. Recently, attention has focused on fat patterning and also on hyperinsulinemia as possible risk factors for cardiovascular disease, as well. The case for insulin as a cardiovascular risk factor is bolstered by theoretical considerations related to its possibly atherogenic effects on serum and arterial wall lipids. Empirical evidence for fat patterning and hyperinsulinemia as cardiovascular risk factors rests on six prospective epidemiologic studies, three on fat patterning and three on insulin. Although provocative, none of these studies can be regarded as definitive. In none was a dose-response effect demonstrated, and there are various inconsistencies within and across the studies. Moreover, in none of the studies were hyperinsulinemia and fat patterning evaluated simultaneously. This is of particular importance in view of the well-documented interrelationships between these two variables. For example, insulin resistance and hyperinsulinemia have been found to be greater in women with upper body obesity compared to women with lower body obesity of equivalent degree. Considerable progress has been made recently in understanding the mechanisms of the differential metabolic effects of these two types of obesity. The extent to which fat patterning and hyperinsulinemia are genetic or acquired has received relatively little attention. Further research on this question is warranted since elucidation of any environmental influences on these variables might suggest new clinical and public health control measures.

Adipose Tissue↗

Association of decreased sex hormone binding globulin and cardiovascular risk factors.

Sex hormones play a major role in determining the risk of cardiovascular disease. While earlier studies have shown that reduced sex hormone binding globulin (SHBG) is associated with increased glucose and insulin concentrations in premenopausal women, few data exist on the relationship of SHBG to other cardiovascular risk factors in women. We hypothesized that decreased SHBG would be associated with an atherogenic pattern of cardiovascular risk factors. We measured total testosterone, total estradiol and SHBG, lipids and lipoproteins, glucose and insulin, and systolic and diastolic blood pressure in 96 premenopausal women. Although total testosterone and total estradiol were not related to cardiovascular risk factors, SHBG was negatively associated with triglyceride concentration (r = -0.37) and positively associated with high density lipoprotein cholesterol (HDLC) (r = 0.42). After adjustment for overall adiposity (body mass index) and upper body adiposity (as measured by the ratio of waist-to-hip circumferences), SHBG was still positively related to HDLC, but not to triglyceride. Adjustment for insulin abolished the relationship between SHBG and triglyceride levels, but did not alter the relationship between SHBG and HDLC. Sex hormones were not related to either systolic or diastolic blood pressure.

Adult↗

Parental history of diabetes is associated with increased cardiovascular risk factors.

Serum insulin concentrations are higher in persons with a positive parental history of diabetes than in persons without such a history. Since hyperinsulinemia is associated with both an increased prevalence of hypertension and an atherogenic pattern of serum lipids and lipoproteins, we hypothesized that among nondiabetic persons, a parental history of diabetes would be associated with an atherogenic pattern of cardiovascular risk factors. In the San Antonio Heart Study, a population-based study of cardiovascular disease and diabetes, we examined 549 nondiabetic persons with a parental history of diabetes and 1167 nondiabetic persons without such a history. Compared to persons without a parental history of diabetes, those with such a history had a more atherogenic pattern of cardiovascular risk factors, including higher body mass index, higher systolic and diastolic blood pressures, higher serum insulin and triglyceride concentrations, and lower levels of high density lipoprotein cholesterol. After adjustment for serum insulin concentration, body mass index, and waist-to-hip ratio, the differences in lipids, lipoproteins, and blood pressure between the two parental history groups were no longer statistically significant. Since persons with a parental history of diabetes are more likely to be prediabetics, the present results suggest that prediabetics have an increased risk of coronary heart disease even before they become diabetic. This phenomenon may help explain why the duration of clinical diabetes is only weakly associated with the risk of coronary heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗

Lp(a) is not related to retinopathy in diabetic subjects.

PURPOSE: To examine the association between Lp(a) concentrations and the severity of retinopathy in 22 younger-onset and 48 older-onset diabetic subjects from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a population-based study of diabetic retinopathy. METHODS: We used a subset of the WESDR population with standardized protocols and stereoscopic color fundus photography to determine the severity of diabetic retinopathy in relation to Lp(a) concentrations. Lp(a) concentrations were measured by a monoclonal anti-Lp(a) antibody. RESULTS: Lp(a) levels were not significantly different between younger-onset or older-onset subjects with and without retinopathy. CONCLUSION: Our results do not support a link between higher levels of Lp(a) and severe retinopathy in either younger-onset or older-onset diabetic subjects but this needs confirmation in larger prospective studies.

Adult↗

Evaluation of three potential screening tests for diabetes mellitus in a biethnic population.

We tested the ability of three potential screening tests for diabetes (fasting plasma glucose value greater than or equal to 140 mg/dl, 1-h postglucose (PG) load value greater than or equal to 200 mg/dl, and 2-h PG value greater than or equal to 200 mg/dl) to detect non-insulin-dependent diabetes in 130 diabetic Mexican Americans (MAs) and 50 diabetic Anglo Americans (AA) using the National Diabetes Data Group criteria as the standard. The sensitivity of the fasting plasma glucose (FPG) cutpoint in detecting diabetes was low in both AAs (36.0%) and MAs (59.3%) and was related to the age-adjusted prevalence rates of diabetes in the two ethnic groups (AAs, 4.9%; MAs, 10.9%). The 2-h PG load cutpoint had good sensitivity (greater than 93%) and specificity (greater than 99%) in both ethnic groups. The ethnic difference in the sensitivity of the FPG cutpoint appeared to be related to the greater hyperglycemia of diabetic MAs compared with diabetic AAs. Nearly 30% of diabetic MAs had FPG values greater than or equal to 200 mg/dl as contrasted with only 10% of diabetic AAs. The difference in severity of hyperglycemia between the ethnic groups appears to be unrelated to ethnic differences in adiposity, pharmacologic treatment, or delay in diagnosis, although longer disease duration in MAs may explain part of the difference.

Adult↗

Role of obesity and fat distribution in non-insulin-dependent diabetes mellitus in Mexican Americans and non-Hispanic whites.

Recent data have suggested that central obesity is related positively to the prevalence of non-insulin-dependent diabetes mellitus (NIDDM). We examined whether central obesity (measured by the ratio of subscapular to triceps skinfold) was predictive of NIDDM prevalence independently of overall obesity (measured by body mass index, BMI) in 1231 Mexican Americans and 939 non-Hispanic whites who participated in the San Antonio Heart Study, a population-based survey of diabetes and cardiovascular risk factors. Mexican Americans are characterized by higher rates of NIDDM, greater overall obesity, and more central body fat distribution than age-matched non-Hispanic whites. Using multiple logistic regression with age, ethnicity, BMI, and central obesity as covariates, overall obesity was positively associated with NIDDM prevalence in both sexes (P less than 0.001) but central obesity was related to NIDDM prevalence only in women. Our data suggest that the effect of centrality decreases at higher levels of centrality. While both BMI and centrality narrow the ethnic difference in NIDDM prevalence, Mexican Americans still have an increased risk of NIDDM (odds ratio = 2.33 in men and 1.80 in women), suggesting that other factors, possibly genetic, may also be important determinants of the ethnic differences in NIDDM prevalence.

Adult↗

[Prevalence of diabetes and glucose intolerance in a urban population at a low economic level].

In this report we present the results of an epidemiologic survey performed in a low income urban neighborhood. The study was designed to investigate the prevalence of type II diabetes mellitus (DM) and impaired glucose tolerance (IGT) in this socioeconomic stratum. The study was done using the standard procedure for the oral glucose tolerance test (OGT) and the recommended diagnostic criteria for defining DM and IGT according to the World Health Organization. A neighborhood corresponding to a census tract was selected and defined by a map. The 39 blocks encompassed in the neighborhood were identified and randomized using the statistical package Systat. According to the randomization, a complete household enumeration was performed. All the residents and the family relationships were identified. The individuals that were between 35-64 years of age and were not pregnant, were considered eligible and were interviewed at home and invited to have a physical examination with an OGT. The number of inhabitants in the study was 4411 of whom 931 were eligible: 452 (48.5%) men, 479 (51.5%) women. The response rate for the home interview was 91.7%; for the physical examination with the OGT it was 69.8%. The crude rate prevalence of DM for men was 10.6%, and for women it was 14.8%. The crude rate prevalence of IGT for men was 12.8% and 12.3% for women. These results show that susceptibility to DM and IGT is high in our population and are among the highest in the world.

Adult↗