Abstract Background Hemoglobin A1c (HbA1c) is a marker of cumulative glycemic exposure over the preceding 2- to 3-month period. Whether mild elevations of this biomarker provide prognostic ...information for development of clinically evident type 2 diabetes and cardiovascular disease among individuals at usual risk for these disorders is uncertain. Methods We examined baseline HbA1c levels as a predictor of incident clinical diabetes and cardiovascular disease (nonfatal myocardial infarction, coronary revascularization procedure, ischemic stroke, or death from cardiovascular causes) in a prospective cohort study beginning in 1992 of 26,563 US female health professionals aged 45 years or more without diagnosed diabetes or vascular disease (median follow-up 10.1 years). Results During follow-up, 1238 cases of diabetes and 684 cardiovascular events occurred. In age-adjusted analyses using quintiles of HbA1c, a risk gradient was observed for both incident diabetes and cardiovascular disease. After multivariable adjustment, HbA1c remained a strong predictor of diabetes but was no longer significantly associated with incident cardiovascular disease. In analyses of threshold effects, adjusted relative risks for incident diabetes in HbA1c categories of less than 5.0%, 5.0% to 5.4%, 5.5% to 5.9%, 6.0% to 6.4%, 6.5% to 6.9%, and 7.0% or more were 1.0, 2.9, 12.1, 29.3, 28.2, and 81.2, respectively. Risk associations persisted after additional adjustment for C-reactive protein and after excluding individuals developing diabetes within 2 and 5 years of follow-up. Conclusions These prospective findings suggest that HbA1c levels are elevated well in advance of the clinical development of type 2 diabetes, supporting recent recommendations for lowering of diagnostic thresholds for glucose metabolic disorders. In contrast, the association of HbA1c with incident cardiovascular events is modest and largely attributable to coexistent traditional risk factors.
Does aldosterone have a role in the pathogenesis of essential hypertension? This report from the Framingham Heart Study suggests that it may. Persons with serum aldosterone levels at the high end of ...the normal range had nearly double the risk of the development of hypertension within four years. Thus, serum aldosterone levels may contribute to the risk of hypertension.
Interindividual variations in serum aldosterone levels may contribute to the risk of hypertension.
A substantial body of experimental and clinical evidence implicates mineralocorticoids in the pathogenesis of hypertension.
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In stroke-prone, spontaneously hypertensive rats, increased vascular and cardiac aldosterone expression and tissue levels of aldosterone antedate the development of hypertension itself.
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,
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All known monogenic forms of hypertension in humans can be traced to defects in renal sodium handling.
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Primary hyperaldosteronism, the classic example of aldosterone excess, is an important cause of secondary hypertension.
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Indeed, it has been suggested that primary hyperaldosteronism is more prevalent among hypertensive patients than has previously been recognized,
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although this point has been contested.
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Of great interest is the . . .
OBJECTIVE:--Adiponectin may improve insulin sensitivity, reduce inflammation, and ameliorate glycemic control. However, few studies have evaluated dietary predictors of plasma adiponectin levels, ...especially among subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS--To examine the associations of dietary glycemic load, glycemic index, and fibers with plasma adiponectin levels, we conducted a cross-sectional analysis in 780 diabetic men from the Health Professionals' Follow-up Study. Dietary information was obtained in 1986, 1990, and 1994 using semiquantitative food-frequency questionnaires. RESULTS:--After adjustment for age, BMI, smoking, alcohol consumption, physical activity, aspirin use, HbAsubscript 1c, history of hypertension or hypercholesterolemia, and fiber intake, dietary glycemic index and glycemic load were inversely associated with plasma adiponectin in a dose-dependent fashion (P for trend = 0.005 for glycemic index and 0.004 for glycemic load). Adiponectin levels were 13% lower in the highest quintile of dietary glycemic index than in the lowest quintile. For dietary glycemic load, adiponectin levels were 18% lower in the highest quintile than in the lowest. In contrast, high intake of cereal fiber was associated with increased plasma adiponectin levels, adjusting for lifestyle factors and dietary glycemic load (P for trend = 0.003). Adiponectin levels were 19% higher in the highest quintile than in the lowest quintile. Higher magnesium intake was also associated with increased plasma adiponectin. CONCLUSIONS:--Diets low in glycemic load and high in fiber may increase plasma adiponectin concentrations in diabetic patients.
Polyunsaturated fatty acid intake favorably affects chronic inflammatory-related diseases such as cardiovascular disease; however, high intake of n-6 fatty acids may attenuate the known beneficial ...effects of n-3 fatty acids.
We investigated habitual dietary n-3 fatty acid intake and its interaction with n-6 fatty acids in relation to the plasma inflammatory markers C-reactive protein, interleukin 6, and soluble tumor necrosis factor receptors 1 and 2 (sTNF-R1 and R2) among 405 healthy men and 454 healthy women. After adjustment for other predictors of inflammation, intake of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was inversely associated with plasma levels of sTNF-R1 and sTNF-R2 (P=0.03 and P<0.001, respectively) and somewhat less so for C-reactive protein (P=0.08). n-3 alpha-linolenic acid and n-6 cis-linoleic acid were not significantly related to the inflammatory markers. We found little if any association between n-3 fatty acid (EPA+DHA) intake and tumor necrosis factor receptors among participants with low intake of n-6 but a strong inverse association among those with high n-6 intake (P=0.04 and 0.002 for interaction of n-3 with n-6 on sTNF-R1 and sTNF-R2, respectively).
These results suggest that n-6 fatty acids do not inhibit the antiinflammatory effects of n-3 fatty acids and that the combination of both types of fatty acids is associated with the lowest levels of inflammation. The inhibition of inflammatory cytokines may be one possible mechanism for the observed beneficial effects of these fatty acids on chronic inflammatory-related diseases.
P-selectin, a cell-surface adhesion molecule involved in leukocyte rolling and attachment, has been hypothesized to play a role in the initiation of atherosclerosis. However, little clinical data are ...available evaluating the role of soluble P-selectin in determining vascular risk.
In a large-scale prospective study of apparently healthy women, we measured baseline plasma concentration of soluble P-selectin among 115 participants who subsequently developed cardiovascular events and among 230 age- and smoking-matched participants who remained free of disease during 3.5 years of follow-up. Overall, mean levels of soluble P-selectin were significantly higher at baseline among women who subsequently experienced cardiovascular events compared with those who did not (83.2 versus 69.3 ng/mL; P:=0.003). The risk of future cardiovascular events increased with increasing quartiles of soluble P-selectin (P:=0.02), such that women in the highest quartile at study entry had an age- and smoking-matched relative risk 2.2 times higher than those in the lowest quartile (95% confidence interval, 1.2 to 4.2; P:=0.01). This effect was independent of traditional risk factors. For each quartile increase in soluble P-selectin, the risk of future cardiovascular events increased 28% (P:=0.03) after additional adjustment for obesity, hypertension, hyperlipidemia, diabetes, and exercise frequency. The highest risks were observed among women with the very highest levels of P-selectin (>137.3 ng/mL, the 95th percentile cut point of the control distribution).
Soluble P-selectin levels are elevated among apparently healthy women at risk for future vascular events.
Because LDL-cholesterol (LDL-C) is a modifiable risk for coronary heart disease, its routine measurement is recommended in the evaluation and management of hypercholesterolemia. We critically examine ...here the new homogeneous assays for direct determination of LDL-C.
This review relies on published studies and data of the authors using research and routine methods for LDL-C determination. We review experience with methods from their earlier use in lipid research laboratories through the transition to routine clinical testing and the recent development of homogeneous assays. We focus on comparative evaluations and characterizations and the performance of the assays.
Homogeneous assays seem to be able to meet current National Cholesterol Education Program (NCEP) requirements for LDL-C testing for precision (CV <4%) and accuracy (bias <4%), when samples collected from nonfasting individuals are used. In addition, all five currently available assays have been certified by the Cholesterol Reference Methods Laboratory Network. The homogeneous methods also appear to better classify individuals into NCEP cutpoints than the Friedewald calculation. However, the limited evaluations to date raise questions about their reliability and specificity, especially in samples with atypical lipoproteins.
Available evidence supports recommending the homogeneous assays for LDL-C to supplement the Friedewald calculation in those cases where the calculation is known to be unreliable, e.g., triglycerides >4000 mg/L. Before the homogeneous assays can be confidently recommended to replace the calculation in routine practice, more evaluation is needed.
Background —Elevated plasma concentrations of C-reactive protein (CRP) are associated with increased cardiovascular risk. We evaluated whether long-term therapy with pravastatin, an agent that ...reduces cardiovascular risk, might alter levels of this inflammatory parameter. Methods and Results —CRP levels were measured at baseline and at 5 years in 472 randomly selected participants in the Cholesterol and Recurrent Events (CARE) trial who remained free of recurrent coronary events during follow-up. Overall, CRP levels at baseline and at 5 years were highly correlated ( r =0.60, P <0.001). However, among those allocated to placebo, median CRP levels and the mean change in CRP tended to increase over time (median change, +4.2%; P =0.2 and mean change, +0.07 mg/dL; P =0.04). By contrast, median CRP levels and the mean change in CRP decreased over time among those allocated to pravastatin (median change, −17.4%; P =0.004 and mean change, −0.07 mg/dL; P =0.002). Thus, statistically significant differences were observed at 5 years between the pravastatin and placebo groups in terms of median CRP levels (difference, −21.6%; P =0.007), mean CRP levels (difference, −37.8%; P =0.002), and absolute mean change in CRP (difference, −0.137 mg/dL; P =0.003). These effects persisted in analyses stratified by age, body mass index, smoking status, blood pressure, and baseline lipid levels. Attempts to relate the magnitude of change in CRP to the magnitude of change in lipids in both the pravastatin and placebo groups did not reveal any obvious relationships. Conclusions —Among survivors of myocardial infarction on standard therapy plus placebo, CRP levels tended to increase over 5 years of follow-up. In contrast, randomization to pravastatin resulted in significant reductions in this inflammatory marker that were not related to the magnitude of lipid alterations observed. Thus, these data further support the potential for nonlipid effects of this agent.
Abstract Objective To examine prospectively the association of total and high molecular weight (HMW) adiponectin, and HMW/total adiponectin ratio with risk of incident coronary heart disease (CHD) in ...women, and to examine to what extent adjustment for potentially intermediary variables would explain this association. Methods and results Among 30,111 women from the Nurses’ Health Study, 468 women developed non-fatal myocardial infarction or fatal CHD during 14 years of follow-up. Using risk set sampling, controls were selected 2:1 matched on age, smoking, and date of blood draw. Adjusted for matching factors, parental history of myocardial infarction, hormone replacement therapy, alcohol consumption, physical activity, body mass index, hypertension, and low-density lipoprotein cholesterol levels, the relative risk in the highest versus lowest quintile was 0.50 (95%-CI 0.33–0.75; p trend = 0.001) for total adiponectin, 0.53 (95%-CI 0.35–0.80; p trend = 0.004) for HMW adiponectin, and 0.63 (95%-CI 0.43–0.93; p trend = 0.03) for HMW/total adiponectin ratio. After adjustment for diabetes, HDL-cholesterol, HbA1c, and CRP these associations were attenuated and no longer significant (RRs, 0.84; 95%-CI 0.53–1.33; p trend = 0.62; 0.95; 95%-CI 0.60–1.52; p trend = 0.98; 0.97; 95%-CI 0.64–1.47; p trend = 0.80). Conclusions High levels of total and HMW adiponectin, and HMW/total adiponectin ratio are associated with a lower risk of CHD among women. HMW adiponectin and HMW/total adiponectin ratio are not more closely related to risk than total adiponectin. These associations are largely mediated by parameters related to glucose and lipid metabolism and inflammation, especially HDL-cholesterol levels.