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Major adverse cardiovascular events in diabetics: network meta-analysis of clinical trials comparing antihypertensive drugs
Abstracts / Journal of the American Society of Hypertension 8(4S) (2014) e67–e74
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and structural abnormalities in the Rasmussen Center for Cardiovascular Disease Prevention The 9 non-invasive tests, in addition to BP, include small artery and large artery elasticity, exercise BP response, optic fundus photography, carotid ultrasound, microalbuminuria, ECG, left ventricular ultrasound and NT-ProBNP measurement. A Disease Score (DS) of 0-18 is based on abnormalities in these 9 tests, with DS of 0-2 associated with no future morbid events, DS of 3-5 with morbid events delayed by at least 4 years and DS of 6 experiencing a high morbid event rate beginning immediately. Results: After excluding 632 individuals taking anti-hypertensive drugs 1184 were classified by BP: normal (<120/80 mmHg), n¼403; pre-hypertensive stage I (BP range, 120-129/80-84), n¼476); prehypertensive stage II, (BP range, 130-139/85-89), n¼185); hypertensive (BP 140/ 90), n¼120). Mean Disease Score in these 4 groups were 2.5 2.2, 3.5 2.5, 4.3 2.8 and 5.6 3.3, respectively, thus confirming the population relationship between BP and disease. However, DS of 6 was present in over 10% of the normal group, 22% of prehypertension stage I, 30% of prehypertension stage II and 50% of hypertension. The distribution of BP in each of the Disease Score groups was largely overlapping. Conclusion: BP is not a reliable guide to individual risk for cardiovascular morbid events. Early non-invasive disease assessment provides the opportunity for individualized management of early disease regardless of BP. Keywords: blood pressure; cardiovascular disease; hypertension; early detection
P-111 Major adverse cardiovascular events in diabetics: network metaanalysis of clinical trials comparing antihypertensive drugs Hunter C. Spencer,1 Peter M. Meyer,2 William J. Elliott.1 1Pacific Northwest University of Health Sciences, Yakima, WA, United States; 2 RUSH Medical College, Chicago, IL, United States The American Diabetes Association continues to recommend that all diabetics receive either an angiotensin-converting enzyme (ACE)-inhibitor or an angiotensin II receptor blocker (ARB), presumably because of these agents’ beneficial effects on renal outcomes in type 1 or type 2 diabetics, respectively. To explore potential differences across classes of antihypertensive agents, cardiovascular outcomes data were abstracted from 28 clinical trials in which 78,754 diabetics were randomized to different drug therapies; the combination arms of ONTARGET were excluded. The numbers of subjects experiencing the composite outcome of interest, cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (whichever occurred first) were directly reported by 20 trials, or were estimated from the numbers reported for its components (using multivariate regression analysis) for 8 others (SHEP, ALLHAT, Syst-EUR, Syst-China, INSIGHT, IRMA-2, INVEST, and CASE-J). Network meta-analyses were performed using a slight modification of the one-line R program of Lumley (Stat Med. 2002;21:2313-24), the incoherence value (u) was 0.00000014. The results were:
patients in many of these trials received other antihypertensive agents, in addition to the randomized therapy, which probably dilutes any protective effect of the active agent.
Keyword: ACE-inhibitor
P-112 No changes in plasma uric acid or blood pressure following ten weeks of fructose containing sugar consumption Joshua Lowndes, Zhiping Fullerton, James Rippe. Rippe Lifestyle Institute, Celebration, FL, United States Background: Hyperuricemia may be promoted by consumption of very high doses of fructose, which in turn may increase blood pressure. This relationship has been shown in rodent models, but has only been observed while using high doses of fructose that are inapplicable to human diets. The impact of fructose as commonly consumed by humans - in conjunction with other sugars and nutrients and in much lower amounts - has yet to be defined. Methods: 268 weight-stable (weight change <3% in previous 30 days) individuals aged 20-60 years old drank sugar-sweetened low fat milk every day for 10 weeks as part of their usual, mixed nutrient diet. The amount of milk consumed was individualized for each participant based on the estimated number of calories required to maintain body weight (Mifflin St Jeor equation) and random group assignment: Groups 1 and 2 - 9% estimated caloric intake from fructose or glucose respectively added to milk. Groups 3 and 4 - 18% of estimated caloric intake from HFCS or sucrose respectively added to the milk (50th percentile for consumption levels of fructose in the USA). Fasting blood pressure and a blood sample for the measurement of uric acid was obtained prior to and after the 10-week intervention. In addition, a subset (n¼78) had two overnight visits in our metabolic ward during which standardized meals were provided and blood samples obtained every two hours. Uric acid AUC for each 24-hour period was calculated using the trapezoidal method. Results: Resting blood pressure decreased in the entire cohort of 268 milk drinkers (systolic: 109.2 10.2 vs 106.1 10.4 mm Hg p<0.001, diastolic: 69.8 8.7 vs 68.1 9.7 mm Hg, p<0.01) and there was no change in fasting uric acid (5.0 1.4 vs 4.9 1.3 mg/dL, p>0.05). In the metabolic ward subset, 24-hour AUC for uric acid was not different after ten weeks of sugar sweetened milk consumption (93.6 25.8 vs 96.1 29.1 hr*mg/dL, p>0.05). For all measures there was no effect of sugar type (all interaction effects, p>0.05). Conclusion: We conclude that ten weeks of consumption of fructose at the 50th percentile level, whether consumed as pure fructose or with additional non-fructose sugars, as is commonly the case, does not promote hyperuricemia, or increase blood pressure. Keywords: Fructose; Sugar; Blood Pressure; Uric Acid
P-113 Pre-operative blood pressure management: does it really matter? Mohammad Nour Zabad, Matthew Jonovich, John Bisognano. University of Rochester, Rochester, NY, United States
Drug Class
# of Arms
# of Outcomes/ # At Risk
Odds Ratio (95% CI)
P-value (vs. Placebo)
ACE-inhibitor ARB b-Blocker CCB Diuretic Placebo
12 11 7 15 5 15
2462/18,164 1920/12,278 1078/8.769 1783/16,647 1197/9,797 2520/17,323
0.89 0.92 0.93 0.91 0.91 1.00
0.008 0.11 0.37 0.14 0.14 —
(0.81-0.97) (0.84-1.02) (0.80-1.09) (0.81-1.03) (0.79-1.04) (referent)
CI ¼ confidence interval; CCB ¼ calcium channel blocker. Although differences across active antihypertensive agents were not significant, these data suggest that only an ACE-inhibitor prevented major adverse cardiovascular events in diabetics better than placebo. These data are confounded by the fact that placebo-treated
Hypertension is frequently encountered among patients immediately before or shortly after surgical procedures and is the most common medical reason for postponing elective surgery. To date there exist no clear guidelines for the management of perioperative hypertension. The aim of this study was to evaluate if elevated blood pressure in the perioperative period has an incremental effect on adverse cardiovascular events. A retrospective chart analysis was conducted on 152 patients who underwent cardiac or vascular surgery at a single tertiary care center with documented systolic hypertension occurring 24 hours before or within 7 days after surgery. Subjects were stratified into two groups based on maximum systolic blood pressure SBP: 140-179mmHg (n¼90); SBP>180mmHg (n¼62) and
e70
and structural abnormalities in the Rasmussen Center for Cardiovascular Disease Prevention The 9 non-invasive tests, in addition to BP, include small artery and large artery elasticity, exercise BP response, optic fundus photography, carotid ultrasound, microalbuminuria, ECG, left ventricular ultrasound and NT-ProBNP measurement. A Disease Score (DS) of 0-18 is based on abnormalities in these 9 tests, with DS of 0-2 associated with no future morbid events, DS of 3-5 with morbid events delayed by at least 4 years and DS of 6 experiencing a high morbid event rate beginning immediately. Results: After excluding 632 individuals taking anti-hypertensive drugs 1184 were classified by BP: normal (<120/80 mmHg), n¼403; pre-hypertensive stage I (BP range, 120-129/80-84), n¼476); prehypertensive stage II, (BP range, 130-139/85-89), n¼185); hypertensive (BP 140/ 90), n¼120). Mean Disease Score in these 4 groups were 2.5 2.2, 3.5 2.5, 4.3 2.8 and 5.6 3.3, respectively, thus confirming the population relationship between BP and disease. However, DS of 6 was present in over 10% of the normal group, 22% of prehypertension stage I, 30% of prehypertension stage II and 50% of hypertension. The distribution of BP in each of the Disease Score groups was largely overlapping. Conclusion: BP is not a reliable guide to individual risk for cardiovascular morbid events. Early non-invasive disease assessment provides the opportunity for individualized management of early disease regardless of BP. Keywords: blood pressure; cardiovascular disease; hypertension; early detection
P-111 Major adverse cardiovascular events in diabetics: network metaanalysis of clinical trials comparing antihypertensive drugs Hunter C. Spencer,1 Peter M. Meyer,2 William J. Elliott.1 1Pacific Northwest University of Health Sciences, Yakima, WA, United States; 2 RUSH Medical College, Chicago, IL, United States The American Diabetes Association continues to recommend that all diabetics receive either an angiotensin-converting enzyme (ACE)-inhibitor or an angiotensin II receptor blocker (ARB), presumably because of these agents’ beneficial effects on renal outcomes in type 1 or type 2 diabetics, respectively. To explore potential differences across classes of antihypertensive agents, cardiovascular outcomes data were abstracted from 28 clinical trials in which 78,754 diabetics were randomized to different drug therapies; the combination arms of ONTARGET were excluded. The numbers of subjects experiencing the composite outcome of interest, cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (whichever occurred first) were directly reported by 20 trials, or were estimated from the numbers reported for its components (using multivariate regression analysis) for 8 others (SHEP, ALLHAT, Syst-EUR, Syst-China, INSIGHT, IRMA-2, INVEST, and CASE-J). Network meta-analyses were performed using a slight modification of the one-line R program of Lumley (Stat Med. 2002;21:2313-24), the incoherence value (u) was 0.00000014. The results were:
patients in many of these trials received other antihypertensive agents, in addition to the randomized therapy, which probably dilutes any protective effect of the active agent.
Keyword: ACE-inhibitor
P-112 No changes in plasma uric acid or blood pressure following ten weeks of fructose containing sugar consumption Joshua Lowndes, Zhiping Fullerton, James Rippe. Rippe Lifestyle Institute, Celebration, FL, United States Background: Hyperuricemia may be promoted by consumption of very high doses of fructose, which in turn may increase blood pressure. This relationship has been shown in rodent models, but has only been observed while using high doses of fructose that are inapplicable to human diets. The impact of fructose as commonly consumed by humans - in conjunction with other sugars and nutrients and in much lower amounts - has yet to be defined. Methods: 268 weight-stable (weight change <3% in previous 30 days) individuals aged 20-60 years old drank sugar-sweetened low fat milk every day for 10 weeks as part of their usual, mixed nutrient diet. The amount of milk consumed was individualized for each participant based on the estimated number of calories required to maintain body weight (Mifflin St Jeor equation) and random group assignment: Groups 1 and 2 - 9% estimated caloric intake from fructose or glucose respectively added to milk. Groups 3 and 4 - 18% of estimated caloric intake from HFCS or sucrose respectively added to the milk (50th percentile for consumption levels of fructose in the USA). Fasting blood pressure and a blood sample for the measurement of uric acid was obtained prior to and after the 10-week intervention. In addition, a subset (n¼78) had two overnight visits in our metabolic ward during which standardized meals were provided and blood samples obtained every two hours. Uric acid AUC for each 24-hour period was calculated using the trapezoidal method. Results: Resting blood pressure decreased in the entire cohort of 268 milk drinkers (systolic: 109.2 10.2 vs 106.1 10.4 mm Hg p<0.001, diastolic: 69.8 8.7 vs 68.1 9.7 mm Hg, p<0.01) and there was no change in fasting uric acid (5.0 1.4 vs 4.9 1.3 mg/dL, p>0.05). In the metabolic ward subset, 24-hour AUC for uric acid was not different after ten weeks of sugar sweetened milk consumption (93.6 25.8 vs 96.1 29.1 hr*mg/dL, p>0.05). For all measures there was no effect of sugar type (all interaction effects, p>0.05). Conclusion: We conclude that ten weeks of consumption of fructose at the 50th percentile level, whether consumed as pure fructose or with additional non-fructose sugars, as is commonly the case, does not promote hyperuricemia, or increase blood pressure. Keywords: Fructose; Sugar; Blood Pressure; Uric Acid
P-113 Pre-operative blood pressure management: does it really matter? Mohammad Nour Zabad, Matthew Jonovich, John Bisognano. University of Rochester, Rochester, NY, United States
Drug Class
# of Arms
# of Outcomes/ # At Risk
Odds Ratio (95% CI)
P-value (vs. Placebo)
ACE-inhibitor ARB b-Blocker CCB Diuretic Placebo
12 11 7 15 5 15
2462/18,164 1920/12,278 1078/8.769 1783/16,647 1197/9,797 2520/17,323
0.89 0.92 0.93 0.91 0.91 1.00
0.008 0.11 0.37 0.14 0.14 —
(0.81-0.97) (0.84-1.02) (0.80-1.09) (0.81-1.03) (0.79-1.04) (referent)
CI ¼ confidence interval; CCB ¼ calcium channel blocker. Although differences across active antihypertensive agents were not significant, these data suggest that only an ACE-inhibitor prevented major adverse cardiovascular events in diabetics better than placebo. These data are confounded by the fact that placebo-treated
Hypertension is frequently encountered among patients immediately before or shortly after surgical procedures and is the most common medical reason for postponing elective surgery. To date there exist no clear guidelines for the management of perioperative hypertension. The aim of this study was to evaluate if elevated blood pressure in the perioperative period has an incremental effect on adverse cardiovascular events. A retrospective chart analysis was conducted on 152 patients who underwent cardiac or vascular surgery at a single tertiary care center with documented systolic hypertension occurring 24 hours before or within 7 days after surgery. Subjects were stratified into two groups based on maximum systolic blood pressure SBP: 140-179mmHg (n¼90); SBP>180mmHg (n¼62) and