Testosterone and Cardiovascular Disease Kloner, Robert A., MD, PhD; Carson, Culley, MD; Dobs, Adrian, MD ...
Journal of the American College of Cardiology,
02/2016, Letnik:
67, Številka:
5
Journal Article
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Abstract Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral ...density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are associated with more atherosclerosis, coronary artery disease, and cardiovascular events. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events. Emerging studies suggest that T may have a future role in treating heart failure, angina, and myocardial ischemia. A large, prospective, long-term study of T replacement, with a primary endpoint of a composite of adverse cardiovascular events including myocardial infarction, stroke, and/or cardiovascular death, is needed. The Food and Drug Administration recently put additional restrictions on T replacement therapy labeling and called for additional studies to determine its cardiac safety.
The impact of diet on cardiovascular disease has become an increasingly relevant topic as ongoing epidemiological evidence continues to demonstrate clear associations with disease burden and ...mortality. Certain diets, such as those high in sodium and saturated fat, are associated with cardiovascular disease states, while other diets can be cardioprotective. However, there is limited knowledge on how the micro- and macronutrients within such cardioprotective diets afford their benefits. One such micronutrient is the catechin class, which are naturally occurring compounds in plant foods, such as teas, cocoa, wine, pears, and apples. Recent evidence reveals that catechins may be a key mediator in cardiovascular health via mechanisms of blood pressure reduction, flow-mediated vasodilation, and atherosclerosis attenuation. This review evaluates the current literature on the interplay between catechins and cardiovascular disease, which may have important implications for nutrition counseling and pharmaceutical drug development.
IMPORTANCE: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. OBJECTIVE: To test the hypothesis that testosterone treatment of older ...men with low testosterone slows progression of noncalcified coronary artery plaque volume. DESIGN, SETTING, AND PARTICIPANTS: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. INTERVENTION: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). RESULTS: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, −27 Agatston units; 95% CI, −80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. CONCLUSIONS AND RELEVANCE: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799617
In this trial, 1015 patients were assigned to the use of either a genotype-guided algorithm or a clinically guided algorithm for warfarin dosing during the first 5 days. At 4 weeks, there was no ...significant difference in the percentage of time in the therapeutic INR range.
The need for clinical trials before widespread adoption of genotype-guided drug dosing and selection remains widely debated.
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Warfarin therapy has served as a model for the potential for pharmacogenetics to improve patient care.
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Observational studies have identified two genes,
CYP2C9
and
VKORC1,
that are associated with variation in warfarin maintenance doses. However, the clinical utility of starting warfarin at the maintenance dose predicted by genotype-guided algorithms has been tested only in small trials, none of which were definitive.
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In contrast, observational studies have suggested potential benefits from genotype-guided dosing.
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In addition, previous clinical trials could not determine . . .
Lessons From the Testosterone Trials Snyder, Peter J; Bhasin, Shalender; Cunningham, Glenn R ...
Endocrine reviews,
2018-June, Letnik:
39, Številka:
3
Journal Article
Recenzirano
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Abstract
The Testosterone Trials (TTrials) were a coordinated set of seven placebo-controlled,
double-blind trials in 788 men with a mean age of 72 years to determine the efficacy of
increasing the ...testosterone levels of older men with low testosterone. Testosterone
treatment increased the median testosterone level from unequivocally low at baseline to
midnormal for young men after 3 months and maintained that level until month 12. In the
Sexual Function Trial, testosterone increased sexual activity, sexual desire, and erectile
function. In the Physical Function Trial, testosterone did not increase the distance
walked in 6 minutes in men whose walk speed was slow; however, in all TTrial participants,
testosterone did increase the distance walked. In the Vitality Trial, testosterone did not
increase energy but slightly improved mood and depressive symptoms. In the Cognitive
Function Trial, testosterone did not improve cognitive function. In the Anemia Trial,
testosterone increased hemoglobin in both men who had anemia of a known cause and in men
with unexplained anemia. In the Bone Trial, testosterone increased volumetric bone mineral
density and the estimated strength of the spine and hip. In the Cardiovascular Trial,
testosterone increased the coronary artery noncalcified plaque volume as assessed using
computed tomographic angiography. Although testosterone was not associated with more
cardiovascular or prostate adverse events than placebo, a trial of a much larger number of
men for a much longer period would be necessary to determine whether testosterone
increases cardiovascular or prostate risk.
The Testosterone Trials were conducted to determine if testosterone treatment would
benefit older men with low testosterone. This report describes the Trials' development and
results and the lessons learned.
Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the ...risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited.
In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point CV death, myocardial infarction (MI), and stroke, as well as other CV and non-CV events, were assessed.
The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915-1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5-2.2); for CV death, 2.63 (1.9-3.6); for sudden death, 3.06 (1.9-4.8); for heart failure (HF) death, 4.3 (1.3-14); for cancer death, 2.5 (1.3-4.7); for hospitalization for HF, 5.8 (3.2-10); for MI 1.4 (95% CI, 1.1-1.9); and for stroke, 1.8 (95% CI, 1.1-2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI.
In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903.
OBJECTIVE: The association between platelet activity, diabetes, and glucometabolic control is uncertain. We aim to investigate mean platelet volume (MPV), a marker of platelet size and platelet ...activity, with the prevalence of diabetes, metabolic syndrome, and degree of glycemic control. RESEARCH DESIGN AND METHODS: This is a retrospective analysis of 13,021 participants in the National Health and Nutrition Examination Survey from 1999 to 2004. Prevalence of diabetes was defined as nonfasting glucose >200 mg/dL, fasting glucose ≥126 mg/dL, or treatment with hypoglycemic agents. Presence of metabolic syndrome was determined by the National Cholesterol Education Program Adult Treatment Panel III definition. Odds ratios and 95% CIs were estimated by logistic regression. RESULTS: MPV was significantly higher in subjects with diabetes (8.20 vs. 8.06 femtoliter fL, P < 0.01) but not in subjects with metabolic syndrome (8.09 vs. 8.07 fL, P = 0.24). For the metabolic syndrome components, MPV was significantly higher in abdominal obesity (P = 0.03) and low HDL (P = 0.04), and not different in high blood pressure (P = 0.07), abnormal glucose metabolism (P = 0.71), or hypertriglyceridemia (P = 0.46). There was a significant correlation between MPV and glucose (P < 0.0001) and between MPV and hemoglobin A1C (P < 0.0001) in subjects with diabetes. These correlations were no longer significant in those without diabetes. The adjusted odds of diabetes rose with increasing MPV levels and were most pronounced in subjects with MPV levels exceeding the 90th percentile (≥9.31 fL). The association between MPV and diabetes was most apparent in those with the poorest glucose control. CONCLUSIONS: Mean platelet volume is strongly and independently associated with the presence and severity of diabetes.
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