Journal of Cardiovascular Pharmacology and Therapeutics

A low n-3 to n-6 polyunsaturated fatty acids (PUFAs) ratio is reported to be associated with cardiovascular events. However, the effects of statins on this ratio have not been fully examined.

A total of 101 patients with coronary artery disease, who were not receiving lipid-lowering therapy were randomly assigned to receive either 4 mg/day of pitavastatin or 20 mg/day of pravastatin. Serum PUFA levels were measured at baseline and 8 months after treatment with statins.

Pitavastatin was used to treat 51 patients and the remaining 50 patients were treated using pravastatin. A significant positive correlation was observed between the percent change in low-density lipoprotein cholesterol and that in dihomogamma-linolenic acid (r = .376, P = .007), arachidonic acid (AA; r = .316, P = .02), eicosapentaenoic acid (EPA; r = .408, P = .003), or docosahexaenoic acid (DHA; r = .270, P = .056) in the pitavastatin group. However, these correlations were not observed in the pravastatin group. The DHA/AA ratio decreased significantly in the pitavastatin group only (from 0.96 to 0.83, P = .0002) and the DHA/AA ratio was significantly lower in the pitavastatin group at 8 months (0.83 vs 0.96, P = .03). The EPA/AA ratio did not show significant changes in either group.

Pitavastatin decreased the serum DHA/AA ratio, whereas pravastatin had no effect on this ratio. Neither pitavastatin nor pravastatin had an effect on the serum EPA/AA ratio in patients with coronary artery disease.

A high loading dose of atorvastatin has been confirmed to reduce postprocedural events in patients undergoing percutaneous coronary intervention (PCI). In this study, we sought to investigate the protective effects of rosuvastatin in patients with acute coronary syndromes (ACS) undergoing PCI and to determine the effect of rosuvastatin pretreatment on the postprocedural levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and monocyte chemotactic protein 1 (MCP-1).

A total of 125 patients with non-ST-segment elevation ACS were randomized to pretreatment with rosuvastatin (20 mg 2-4 hours before PCI [n = 62]) or placebo (n = 63). All the patients received subsequent long-term rosuvastatin treatment (10 mg/d). The main end point of the trial was the 30-day incidence of major adverse cardiac events (death, myocardial infarction, or unplanned revascularization). Plasma levels of hs-CRP, IL-6, and MCP-1 were detected before PCI and 6 hours, 24 hours, and 3 days after PCI.

The primary end point occurred in 8.1% of the patients in the rosuvastatin arm and 22.2% in the placebo arm (P < .01); this difference was entirely attributed to a reduced incidence of myocardial infarction (8.1% vs 22.2%; P < .01). The postprocedural elevation in creatine kinase-MB and troponin I was also significantly lower in the rosuvastatin group at 6 hours, 24 hours, and 3 days. Plasma levels of hs-CRP, IL-6, and MCP-1 increased significantly after PCI in both the rosuvastatin and control groups; however, the postprocedural elevations in hs-CRP and IL-6 levels were significantly lower in the rosuvastatin group than the control group.

A single, high dose (20 mg) of rosuvastatin prior to PCI reduces postprocedural myocardial injury in patients with ACS, with a concomitant attenuation of the postprocedural increase in hs-CRP and IL-6 levels.

Hypoalbuminemia is believed to decrease diuretic effectiveness and contribute to diuretic resistance that is observed in patients with nephrotic syndrome. Hypoalbuminemia is also seen in patients with acute decompensated heart failure (ADHF). However, the role of hypoalbuminemia on the effectiveness of continuous infusion diuretics in patients with ADHF is not known.

To evaluate hypoalbuminemia (albumin ≤3 g/dL) and diuretic effectiveness, we performed a retrospective study in 162 patients admitted to a tertiary care center for treatment of ADHF over a 3-year period. All patients received continuous infusion diuretic for at least a 2-day time period.

A total of 33 patients were determined to have hypoalbuminemia. Average net urine output over a 2-day study period was similar between patients with and without hypoalbuminemia (−1462 ± 1734 vs −1233 ± 1560 mL, P = .46, respectively). In addition, diuretic doses (furosemide equivalent/24 hours) were similar between the 2 groups (788 ± 671 vs 778 ± 713 mg, P = .91, respectively) as was baseline serum creatinine (1.6 ± 0.6 vs 1.6 ± 0.6 mg/dL, P = .5, respectively).

Overall, hypoalbuminemia did not decrease the diuretic effectiveness when measured by the net urine output in patients receiving continuous infusion diuretics for the treatment of ADHF.

Inappropriate sinus tachycardia (IST) is a clinical syndrome characterized by excessive resting heart rate (HR) or a disproportional increase in HR during exercise. β-blocker or calcium channel-blocker therapy is often noneffective or not well tolerated. The HR reduction on ivabradine is similar to β-blockers but in some patients its efficacy to resolve all IST-related symptoms is limited. The aim of the study was to assess the efficacy and safety of combining ivabradine with metoprolol succinate in patients with refractory highly symptomatic IST.

Twenty patients (36 ± 10 years; 16 women) with IST were enrolled. All patients received metoprolol succinate 95 mg single dose during the first month of the study. After 4 weeks of treatment with metoprolol, ivabradine was administered as adjuvant therapy up to 7.5 mg twice daily. Holter monitoring and treadmill stress test were performed at baseline, after 4, and 8 weeks of the study, respectively.

We observed significant and similar reduction in resting HR both for metoprolol and for combined therapy compared to the baseline. The mean HR during daily activity was significantly lower on ivabradine and metoprolol compared to monotherapy with β-blocker. The combined treatment yielded a significant increase in exercise capacity as assessed by treadmill stress test. After 4 weeks of combined therapy a significant reduction in IST-related symptoms, measured by means of the European Heart Rhythm Association score, was observed.

Combining ivabradine with metoprolol is an effective and well-tolerated treatment option for IST in patients with refractory to monotherapy.

Limited data exist comparing the efficacy and safety of bumetanide- or metolazone-based diuretic regimens to furosemide in acute heart failure (HF). Our purpose was to evaluate the comparative effect on urine output (UO) and renal function between these regimens.

A retrospective study of hospitalized HF patients treated with continuous infusion furosemide (CIF), combination furosemide plus metolazone (F + M), or continuous infusion bumetanide (CIB). Primary end points were between regimen comparisons for change in mean hourly UO versus baseline and incidence of worsening renal function.

Data on 242 patients with acute HF (age 58 ± 12 years, 63% male, left ventricular ejection fraction 38% ± 17%) were analyzed (160 CIF, 42 F + M, 40 CIB). The mean duration of diuretic regimens was 41 ± 32 hours. Compared to baseline, all regimens increased mean hourly UO (P < .0001 for all), with greater increases with F + M (109 ± 171 mL) and CIB (90 ± 90 mL) compared to CIF (48 ± 103 mL; P = .009). Incidence of worsening renal function was not different between regimens; however, blood urea nitrogen (BUN) tended to increase more with F + M (4.4 ± 9.8 mg/dL) and CIB (4.3 ± 9.7 mg/dL) than CIF (1.8 ± 10.8 mg/dL), P = .09. The incidence of hyponatremia was higher with F + M and CIB. Differences in UO, BUN, and hyponatremia were retained in the subgroup analysis limited to patients with baseline serum creatinine <1.5 mg/dL, where renal function between the groups was not different.

Compared to CIF, F + M or CIB was associated with greater increases in UO. No difference in the incidence of worsening renal function was found; however, electrolyte abnormalities may be more prevalent when furosemide is combined with metolazone or when bumetanide is used. These therapeutic differences warrant prospective study.

According to the literature, estradiol has a direct vasodilator action by means of endothelium-derived relaxing factor synthesis. The present study aims to evaluate the acute hemodynamic effects of intranasal 17-β-estradiol on cerebral and lower limb arterial circulation in postmenopausal women.

Sixteen healthy women in natural menopause (mean age: 54 ± 3 years) were investigated for at least 6 months, each receiving 300 µg of intranasal 17-β-estradiol. We evaluated the heart rate, systolic/diastolic blood pressure, peak systolic velocity, end-diastolic velocity, and velocity–time integral (VTI) at the level of internal carotid and posterior tibial arteries, before and after 30, 60, and 180 minutes of drug administration.

After intranasal 17-β-estradiol administration, the internal carotid artery VTI showed statistically significant (P < .05) variations at all the time intervals after administration of the drug (30, 60, and 180 minutes) when compared with “time zero” (T0, ie, the speed recorded at baseline before drug administration). No significant variation was found at the posterior tibial artery. The systolic/diastolic blood pressure and heart rate did not significantly differ before and after drug administration.

The administration of a single intranasal dose of 17-β-estradiol in healthy postmenopausal women increased cerebral perfusions, whereas the effect on peripheral circulation was much more limited.

Calcitriol (CAL), an active form of vitamin D, plays a vital role in controlling cardiac hypertrophy and heart failure. The aim of the present study is to explore the effects of CAL and to elucidate its underlying mechanisms on myocardial injury induced by isoproterenol (ISO).

Myocardial impairment was induced by the subcutaneous injection of ISO in adult male Sprague-Dawley rats, and the therapeutic effect of CAL was assessed. Biometric and echocardiographic parameters, interstitial fibrosis, oxidant–antioxidant status, and protein expression relevant to the mitochondrial apoptosis pathway were then measured.

Calcitriol treatment improved the cardiac injury resulting from excessive ISO stimulation, as supported by the suppression of the development of myocardial hypertrophy, interstitial fibrosis, and H₂O₂ level in heart tissue. The decreased superoxide dismutase and catalase activities induced by ISO were also improved by CAL. Finally, the administration of CAL downregulated the protein expression of Bax and caspase-9.

This study provides evidence that CAL ameliorated cardiac hypertrophy, interstitial fibrosis, and oxidative stress in ISO-induced cardiac injury and might play a vital cardioprotective role in such injuries.