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Articles by R. J Glynn
Total Records ( 5 ) for R. J Glynn
  W. G Christen , R. J Glynn , H. D Sesso , T Kurth , J MacFadyen , V Bubes , J. E Buring , J. E Manson and J. M. Gaziano
 

Objective  To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of age-related cataract in a large cohort of men.

Methods  In a randomized, double-masked, placebo-controlled trial, 11 545 apparently healthy US male physicians 50 years or older without a diagnosis of cataract at baseline were randomly assigned to receive 400 IU of vitamin E or placebo on alternate days and 500 mg of vitamin C or placebo daily.

Main Outcome Measure  Incident cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review.

Application to Clinical Practice  Long-term use of vitamin E and C supplements has no appreciable effect on cataract.

Results  After 8 years of treatment and follow-up, 1174 incident cataracts were confirmed. There were 579 cataracts in the vitamin E–treated group and 595 in the vitamin E placebo group (hazard ratio, 0.99; 95% confidence interval, 0.88-1.11). For vitamin C, there were 593 cataracts in the treated group and 581 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14).

Conclusion  Long-term alternate-day use of 400 IU of vitamin E and daily use of 500 mg of vitamin C had no notable beneficial or harmful effect on the risk of cataract.

Trial Registration  clinicaltrials.gov Identifier: NCT00270647

  B. M Everett , R. J Glynn , J. G MacFadyen and P. M Ridker
 

Background— Prior primary prevention trials of statin therapy that used cholesterol criteria for enrollment have not reported significant decreases in stroke risk. We evaluated whether statin therapy might reduce stroke rates among individuals with low levels of cholesterol but elevated levels of high-sensitivity C-reactive protein.

Methods and Results— In Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), 17 802 apparently healthy men and women with low-density lipoprotein cholesterol levels <130 mg/dL and high-sensitivity C-reactive protein levels ≥2.0 mg/L were randomly allocated to rosuvastatin 20 mg daily or placebo and then followed up for the occurrence of a first stroke. After a median follow-up of 1.9 years (maximum, 5.0 years), rosuvastatin resulted in a 48% reduction in the hazard of fatal and nonfatal stroke as compared with placebo (incidence rate, 0.18 and 0.34 per 100 person-years of observation, respectively; hazard ratio 0.52; 95% confidence interval, 0.34 to 0.79; P=0.002), a finding that was consistent across all examined subgroups. This finding was due to a 51% reduction in the rate of ischemic stroke (hazard ratio, 0.49; 95% confidence interval, 0.30 to 0.81; P=0.004), with no difference in the rates of hemorrhagic stroke between the active and placebo arms (hazard ratio, 0.67; 95% confidence interval, 0.24 to 1.88; P=0.44).

Conclusion— Rosuvastatin reduces by more than half the incidence of ischemic stroke among men and women with low levels of low-density lipoprotein cholesterol levels who are at risk because of elevated levels of high-sensitivity C-reactive protein.

Clinical Trial Registration— clinicaltrial.gov. Unique identifier: NCT00239681.

  S Mora , R. J Glynn , J Hsia , J. G MacFadyen , J Genest and P. M Ridker
 

Background— Statin therapy in women without cardiovascular disease (CVD) is controversial, given the insufficient evidence of benefit. We analyzed sex-specific outcomes in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and synthesized the results with prior trials.

Methods and Results— JUPITER participants included 6801 women ≥60 years of age and 11 001 men ≥50 years of age with high-sensitivity C-reactive protein ≥2 mg/L and low-density lipoprotein cholesterol <130 mg/dL randomized to rosuvastatin versus placebo. Meta-analysis studies were randomized placebo-controlled statin trials with predominantly or exclusively primary prevention in women and sex-specific outcomes (20 147 women; >276 CVD events; mean age, 63 to 69 years). Absolute CVD rates (per 100 person-years) in JUPITER women for rosuvastatin and placebo (0.57 and 1.04, respectively) were lower than for men (0.88 and 1.54, respectively), with similar relative risk reduction in women (hazard ratio, 0.54; 95% confidence interval, 0.37 to 0.80; P=0.002) and men (hazard ratio, 0.58; 95% confidence interval, 0.45 to 0.73; P<0.001). In women, there was significant reduction in revascularization/unstable angina and nonsignificant reductions in other components of the primary end point. Meta-analysis of 13 154 women (240 CVD events; 216 total deaths) from exclusively primary prevention trials found a significant reduction in primary CVD events with statins by a third (relative risk, 0.63; 95% confidence interval, 0.49 to 0.82; P<0.001; P for heterogeneity=0.56) with a smaller nonsignificant effect on total mortality (relative risk, 0.78; 95% confidence interval, 0.53 to 1.15; P=0.21; P for heterogeneity=0.20). Similar results were obtained for trials that were predominantly but not exclusively primary prevention.

Conclusion— JUPITER demonstrated that in primary prevention rosuvastatin reduced CVD events in women with a relative risk reduction similar to that in men, a finding supported by meta-analysis of primary prevention statin trials.

Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

  P. M Ridker , F. A.H Fonseca , J Genest , A. M Gotto , J. J.P Kastelein , W Koenig , P Libby , A. J Lorenzatti , B. G Nordestgaard , J Shepherd , J. T Willerson , R. J Glynn and for the JUPITER Study Group
 

Background— As recently demonstrated, random allocation to rosuvastatin results in large relative risk reductions for first cardiovascular events among apparently healthy men and women with low levels of low-density lipoprotein cholesterol but elevated levels of high-sensitivity C-reactive protein. However, whether the absolute risk reduction among such individuals justifies wide application of statin therapy in primary prevention is a controversial issue with broad policy and public health implications.

Methods and Results— Absolute risk reductions and consequent number needed to treat (NNT) values were calculated across a range of end points, timeframes, and subgroups using data from Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), a randomized evaluation of rosuvastatin 20 mg versus placebo conducted among 17 802 apparently healthy men and women with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L. Sensitivity analyses were also performed to address the potential impact that alternative statin regimens might have on a similar primary prevention population. For the end point of myocardial infarction, stroke, revascularization, or death, the 5-year NNT within JUPITER was 20 (95% CI, 14 to 34). All subgroups had 5-year NNT values for this end point below 50; as examples, 5-year NNT values were 17 for men and 31 for women, 21 for whites and 19 for nonwhites, 18 for those with body mass index ≤25 kg/m2 and 21 for those with body mass index greater than 25 kg/m2, 9 and 26 for those with and without a family history of coronary disease, 19 and 22 for those with and without metabolic syndrome, and 14 and 37 for those with estimated Framingham risks greater or less than 10%. For the net vascular benefit end point that additionally included venous thromboembolism, the 5-year NNT was 18 (95% CI, 13 to 29). For the restricted "hard" end point of myocardial infarction, stroke, or death, the 5-year NNT was 29 (95% CI, 19 to 56). In sensitivity analyses addressing the theoretical utility of alternative agents, 5-year NNT values of 38 and 57 were estimated for statin regimens that deliver 75% and 50% of the relative benefit observed in JUPITER, respectively. All of these calculations compare favorably to 5-year NNT values previously reported in primary prevention for the use of statins among hyperlipidemic men (5-year NNT, 40 to 70), for antihypertensive therapy (5-year NNT, 80 to 160), or for aspirin (5-year NNT, >300).

Conclusions— Absolute risk reductions and consequent NNT values associated with statin therapy among those with elevated high-sensitivity C-reactive protein and low low-density lipoprotein cholesterol are comparable if not superior to published NNT values for several widely accepted interventions for primary cardiovascular prevention, including the use of statin therapy among those with overt hyperlipidemia.

Clinical Trial Registration— clinicaltrials.gov. Identifier NCT00239681.

  D Conen , R. J Glynn , P. M Ridker , J. E Buring and M. A. Albert
  Aims

The aim of this study was to examine the association between socioeconomic status, blood pressure (BP) progression, and incident hypertension.

Methods and results

We included 27 207 female health professionals free of hypertension and cardiovascular disease at baseline. Participants were classified into five education and six income categories. The main outcome variables were BP progression at 48 months of follow-up and incident hypertension during the entire study period. At 48 months, 48.1% of women had BP progression. The multivariable adjusted relative risks [95% confidence intervals (CIs)] for BP progression were 1.0 (referent), 0.96 (0.92–1.00), 0.92 (0.88–0.96), 0.90 (0.85–0.94), and 0.84 (0.78–0.91) (P for trend <0.0001) across increasing education categories and 1.0 (referent), 1.01 (0.94–1.08), 0.99 (0.93–1.06), 0.97 (0.91–1.04), 0.96 (0.90–1.03), and 0.89 (0.83–0.96) across increasing income categories (P for trend = 0.0001). During a median follow-up of 9.8 years, 8248 cases of incident hypertension occurred. Multivariable adjusted hazard ratios (95% CI) were 1.0 (referent), 0.92 (0.86–0.99), 0.85 (0.79–0.92), 0.87 (0.80–0.94), and 0.74 (0.65–0.84) (P for trend <0.0001) across increasing education categories and 1.0 (referent), 1.07 (0.95–1.21), 1.07 (0.95–1.20), 1.06 (0.94–1.18), 1.04 (0.93–1.16), and 0.93 (0.82–1.06) (P for trend 0.08) across increasing income categories. In joint analyses, education but not income remained associated with BP progression and incident hypertension.

Conclusion

Socioeconomic status, as determined by education but not by income, is a strong independent predictor of BP progression and incident hypertension in women.

 
 
 
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