Effects of pravastatin on cardiovascular reactivity to norepinephrine and angiotensin II in patients with hypercholesterolemia and systemic hypertension

Straznicky, Nora E.; Howes, L. G.; Lam, William; Louis, William J.

doi:10.1016/s0002-9149(99)80621-3

Cited by 76 publications

(52 citation statements)

References 22 publications

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“…In 2 other open-label studies in 49 and 23 hypertensive patients with hypercholesterolemia, fluvastatin significantly decreased systolic and diastolic blood pressures after 12 weeks compared with pretreatment values. 16,18 In a randomized, double-blind, placebo-controlled crossover trial in 7 patients with mild hypertension, 17 3 weeks of treatment with pravastatin blunted the diastolic blood pressure increase induced by angiotensin II and norepinephrine. No significant effect was found on systolic pressure.…”

Section: Discussionmentioning

confidence: 99%

“…12 In theory, by improving endothelial dysfunction, cholesterol reduction with statins may decrease blood pressure in persons with hypertension and hypercholesterolemia. In several animal and human studies, statins decreased resting or stress-induced blood pressure, [13][14][15][16][17][18] but such an effect was not confirmed by other studies. 19 -24 Whether statins can decrease elevated blood pressure in hypertensive patients and whether this mechanism has clinical relevance for event reduction remain unanswered questions.…”

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confidence: 95%

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Effect of the HMG-CoA Reductase Inhibitors on Blood Pressure in Patients With Essential Hypertension and Primary Hypercholesterolemia

et al. 1999

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Abstract-Certain hydroxymethylglutaryl coenzyme A reductase inhibitors, ie, statins, may cause vasodilation by restoring the endothelial dysfunction that frequently accompanies hypertension and hypercholesterolemia. Several studies have found that a blood pressure reduction is associated with the use of statins, but conclusive evidence from controlled trials is lacking. After an 8-week placebo and diet run-in period, 30 persons with moderate hypercholesterolemia and untreated hypertension (total cholesterol 6.29Ϯ0.52 mmol/L, systolic and diastolic blood pressure 149Ϯ6 and 97Ϯ2 mm Hg) were randomized in a double-blind manner to placebo or pravastatin (20 to 40 mg/d) in a crossover design. In 25 participants who completed the 32-week trial, pravastatin decreased total and LDL cholesterol (both Ϫ1.09 mmol/L, Pϭ0.001), systolic and diastolic blood pressure (Ϫ8 and Ϫ5 mm Hg, both Pϭ0.001), and pulse pressure (Ϫ3 mm Hg, Pϭ0.011) and blunted the blood pressure increase caused by the cold pressor test (Ϫ4 mm Hg, Pϭ0.005) compared with placebo. It also reduced the level of circulating endothelin-1 (Pϭ0.001). The blood pressure results were virtually unchanged in stratified analyses according to gender and age and in intention-to-treat analyses that included the 5 patients who dropped out of the study. When the participants were taking either placebo or pravastatin, blood pressure was not significantly correlated with total or LDL cholesterol or with circulating endothelin-1. Pravastatin decreases systolic, diastolic, and pulse pressures in persons with moderate hypercholesterolemia and hypertension. This antihypertensive effect may contribute to the documented health benefits of certain statins. (Hypertension. 1999;34:1281-1286.)Key Words: statins Ⅲ blood pressure Ⅲ cholesterol Ⅲ endothelin Ⅲ hypertension, essential Ⅲ hypercholesterolemia C ertain statins, or hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are clinically proven to prevent coronary and cerebrovascular events in persons with increased plasma cholesterol levels. 1 In a large primary prevention trial, 2 it has been observed that compared with placebo, pravastatin can decrease the risk of cardiovascular events early after randomization. These findings suggest that in addition to the long-term prevention of atherosclerosis, other more immediate mechanisms might account for the clinical benefits of statins. 3 Several short-term studies have shown that statins can improve endothelial function and the endothelium-dependent arterial vasodilation that are typically altered in persons with increased plasma cholesterol levels. 4 -7 Hypercholesterolemia, endothelial dysfunction, and hypertension are frequently coexisting conditions, even in the absence of documented atherosclerotic lesions. 8 -11 Moreover, recent animal data indicate that the effect of pravastatin on the endothelium might be due in part to nonlipid effects. 12 In theory, by improving endothelial dysfunction, cholesterol reduction with statins may decrease blood pressure in persons wi...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

Effect of the HMG-CoA Reductase Inhibitors on Blood Pressure in Patients With Essential Hypertension and Primary Hypercholesterolemia

et al. 1999

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“…Eighteen randomized, controlled trials met the inclusion criteria and were included in the meta-analysis 9,10,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] (Figure 1). Because 2 of them, 25,26 however, were characterized by having 2 different pairs of control and treatment groups, we considered them as being split in 2 independent studies; thus, the final number of studies analyzed was actually 20.…”

Section: Inclusion and Exclusion Criteriamentioning

confidence: 99%

“…One study 9 used probucol, a lipid-lowering drug as control, whereas in another one 26 fluvastatin plus orlistat (an inhibitor of intestinal lipid digestion) were compared with orlistat alone. Pravastatin was the statin used in 8 studies, 9,10,17,[21][22][23]25 simvastatin was used in 5, 15,19,20,24,28 fluvastatin in 2, 26 cerivastatin in 2 studies, 27,30 atorvastatin in 2 studies, 16,29 and lovastatin in 1 study. 18 The duration of treatment varied from 4 weeks 15 to 1 year.…”

Section: Characteristics Of Trials and Patients Included In The Meta-mentioning

confidence: 99%

“…24,26 Some studies included only hypertensive patients, 10,16,17,23,28,29 others recruited either normotensive or treated hypertensive patients in reasonably good control, 22,30 and a few studies included only normotensive individuals. 22,23,28,30 Four studies included only type 1 or only type 2 diabetic patients, 19,24,27,30 whereas 9 studies excluded patients affected by diabetes 9,10,15,17,18,20,21,23,29 (Table S3).…”

Section: Characteristics Of Trials and Patients Included In The Meta-mentioning

confidence: 99%

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Do Statins Reduce Blood Pressure?

et al. 2007

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Abstract-A meta-analysis was performed of the effect of 3hydroxy3methylglutaryl-coenzyme A reductase inhibitors (statins) on blood pressure in humans including the randomized, controlled trials of statin therapy (20 trials and 828 patients) in which concomitant antihypertensive treatment (if any) remained unchanged throughout the study. A total of 291 and 272 patients were given a statin or placebo, respectively, in parallel group trials, whereas 265 took part in crossover trials receiving a statin and placebo (or probucol, in 1 trial). Systolic blood pressure was significantly lower in patients on statin than in those on placebo or control hypolipidemic drug (mean difference: Ϫ1.9 mm Hg; 95% CI: Ϫ3.8 to Ϫ0.1). The effect was greater when the analysis was restricted to studies with a baseline systolic blood pressure Ͼ130 mm Hg (⌬ systolic blood pressure: Ϫ4.0; 95% CI: Ϫ5.8 to Ϫ2.2 mm Hg). There was a trend for lower diastolic blood pressure in patients receiving statin therapy compared with control: Ϫ0.9 mm Hg (95% CI: Ϫ2.0 to 0.2) overall and Ϫ1.2 mm Hg (95% CI: Ϫ2.6 to 0.1) in studies with a baseline diastolic blood pressure Ͼ80 mm Hg. In general, the higher the baseline blood pressure, the greater the effect of statins on blood pressure (Pϭ0.066 for systolic blood pressure and Pϭ0.023 for diastolic blood pressure). The blood pressure response to statins was unrelated to age, changes in serum cholesterol, or length of the trial. In conclusion, statin therapy has a relatively small but statistically significant and clinically meaningful effect on blood pressure. Key Words: blood pressure Ⅲ hypertension, arterial Ⅲ hypercholesterolemia Ⅲ drug therapy Ⅲ statins Ⅲ meta-analysis H igh blood pressure (BP) is common in hypercholesterolemic and in diabetic patients and powerfully contributes to the increase in cardiovascular risk. 1 The prescription of both antihypertensive and cholesterol-lowering drugs is generally required for these patients. Inhibitors of 3hydroxy3methylglutaryl-coenzyme A reductase (statins) are the most effective and widely used cholesterol-lowering drugs in industrialized countries. 2 They significantly reduce the risk of cardiovascular events and death in both primary and secondary prevention of cardiovascular disease. 3,4 Although the long-term benefit by statin treatment is largely attributed to their cholesterol-lowering action, increasing attention focuses on additional actions of these substances, which are independent from 3hydroxy3methylglutaryl-coenzyme A reductase inhibition 5 and might help explain why part of the benefit in terms of cardiovascular protection is already seen shortly after the initiation of therapy. 6,7 Very few relatively small studies have investigated the antihypertensive effect of statins in patients with hypertension associated with hypercholesterolemia. 8 -10 The results of 2 recently published large statin studies, albeit not designed to answer this question, have attracted the interest on this subject. 11,12 Many other studies, also not specifically aimed at ...

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Statins and Blood Pressure

2008

Arch Intern Med

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Effects of pravastatin on cardiovascular reactivity to norepinephrine and angiotensin II in patients with hypercholesterolemia and systemic hypertension

Cited by 76 publications

References 22 publications

Effect of the HMG-CoA Reductase Inhibitors on Blood Pressure in Patients With Essential Hypertension and Primary Hypercholesterolemia

Effect of the HMG-CoA Reductase Inhibitors on Blood Pressure in Patients With Essential Hypertension and Primary Hypercholesterolemia

Do Statins Reduce Blood Pressure?

Statins and Blood Pressure

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