Statins and collateral flow

[Dr.Vad]

Уважаемые коллеги,

недавние изыски турецких коллег показывают, что длительный прием статинов (более 3 мес.) в средних дозах (более 10 мг в пересчете на аторвастатин) ассоциируется с лучшим развитием коллатерального кровотока - еще плюс одна плейотропная функция?:

Statin therapy for less than 3 months had no effect on collateral development (P=0.19); however, patients who were on statin therapy for more than 3 months had significantly better collateral development (P=0.002). Statin therapy had no effect on coronary collateral development in patients having <10 mg atorvastatin-equivalent dose (P=0.13); however, patients having >/=10 mg atorvastatin-equivalent dose had better collateral development (P<0.001). Diabetes mellitus was the only negative predictor for coronary collateral formation (P=0.03).

из Dncer I, Ongun A, Turhan S, Ozdol C, Kumbasar D, Erol C.
Association between the dosage and duration of statin treatment with coronary collateral development.
Coron Artery Dis. 2006 Sep;17(6):561-5.

Другие релевантные публикации:

Dincer I, Ongun A, Turhan S, Ozdol C, Ertas F, Erol C.
Effect of statin treatment on coronary collateral development in patients with diabetes mellitus.
Am J Cardiol. 2006 Mar 15;97(6):772-4.

Sata M, Nishimatsu H, Osuga J, Tanaka K, Ishizaka N, Ishibashi S, Hirata Y, Nagai R.
Statins augment collateral growth in response to ischemia but they do not promote cancer and atherosclerosis.
Hypertension. 2004 Jun;43(6):1214-20.

Pourati I, Kimmelstiel C, Rand W, Karas RH.
Statin use is associated with enhanced collateralization of severely diseased coronary arteries.
Am Heart J. 2003 Nov;146(5):876-81.

Nishikawa H, Miura S, Zhang B, Shimomura H, Arai H, Tsuchiya Y, Saku K.
Pravastatin promotes coronary collateral circulation in patients with coronary artery disease.
Coron Artery Dis. 2002 Nov;13(7):377-81.

[Gilarov]

Говорят, что плеотропные функции не столь уж важны. Все дело только в снижении уровня холестерина.
J Am Coll Cardiol. 2005 Nov 15;46(10):1855-62. Epub 2005 Oct 24. Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis.
Robinson JG, Smith B, Maheshwari N, Schrott H.
OBJECTIVES: This study sought to determine whether statins reduce coronary heart disease (CHD) risk more than other interventions that also primarily lower low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Statins have anti-inflammatory, immunomodulatory, antithrombotic, vascular, and other non-LDL-C-lowering effects. It is unclear whether these pleiotropic effects contribute to cardiovascular risk reduction beyond that expected from LDL-C reduction alone. METHODS: Trials published in English language journals were retrieved by searching Medline (1966 to October 2004), bibliographies, and the author's reference files. Randomized, placebo-controlled trials of interventions to primarily lower LDL-C of three or more years' duration in which clinical disease or death were primary outcomes were used. Information on sample size, treatment type and duration, participant characteristics at baseline, reduction in lipids, and outcome was independently abstracted by two authors (J.R. and N.M.) using a standardized protocol. Data from 5 diet, 3 bile acid sequestrant, 1 surgery, and 10 statin trials, with 81,859 participants, were included in the CHD meta-regression analysis. RESULTS: The regression lines for non-statin and statin trials were similar and consistent with a one-to-one relationship between LDL-C lowering and CHD and stroke reduction over five years of treatment. CONCLUSIONS: The pleiotropic effects of statins do not seem to contribute an additional cardiovascular risk reduction benefit beyond that expected from the degree of LDL-C lowering observed in other trials that primarily lowered LDL-C.

[Dr.Vad]

Уважаемый Михаил Юрьевич,

Это заболеваемость и смертность зависит, а "коллатеральность" от липидов, похоже, не зависит:

There was no relationship between collateral score and LDL levels in the +statin group (r = 0.2, P = .23), the −statin group (r = 0.1, P = .51), or in all subjects (r = −0.02, P = .90). There were no significant differences in collateral scores in subjects with LDL ≤100 compared to those with LDL >100 (1.6 ± 0.9 vs 1.8 ± 1, P = .29). Am Heart J. 2003 Nov;146(5):876-81

КолЛАТЕРАЛьНОЕ действие, однако

[Gilarov]

Интересно, как считали коллатеральность...

[Dr.Vad]

В турецкой и американской публикациях:

Selective coronary angiography was performed using the Judkins technique. Coronary angiograms were reviewed by two experienced interventional cardiologists blinded to clinical information of the patients.

Coronary collaterals were graded according to the Cohen–Rentrop [10] method: as grade 0, no filling of any collateral vessels; grade 1, filling of side branches of the artery to be perfused by collateral vessels without visualization of epicardial segment; grade 2, partial filling of the epicardial artery by collateral vessels; and grade 3, as complete filling of epicardial artery by collateral vessel. Collateral grading was classified as poor collateral development when the collateral grade was grade 0–1 and good collateral development when the grade was 2–3. Collateral grading was performed to the vessel with coronary artery stenosis of >=95% and if the patient had more than one vessel with high-grade stenosis and collateral development; collateral grading had been carried out according to vessel that had better collateral.

For the analysis of the effect of multivessel disease on coronary collateral development, the number of the diseased vessels was identified according to the number of the coronary arteries having >=70% stenosis.

10. Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 1985; 5:587–592.

Швейцарцы, которые не нашли связи между статинизацией и коллатерализацией, пользовали следующее:

Collateral vessel assessment was performed by three different methods in all patients, whereby the principal end point of the study was the functional measurement obtained by pressure or Doppler guide wires (that is, collateral flow index (CFI) expressing collateral flow as a fraction of normal coronary flow).

[Ссылки доступны только зарегистрированным пользователям ]

C. Seiler, M. Fleisch, A.R. Garachemani et al., Coronary collateral quantitation in patients with coronary artery disease using intravascular flow velocity or pressure measurements. J Am Coll Cardiol 32 (1998), pp. 1272–1279

Технические обьяснялки:

IC Doppler flow velocity measurements
Intracoronary Doppler flow velocity measurements were performed using a 0.014 in. ( mm in diameter) PTCA Doppler guidewire with a 12-MHz piezoelectric crystal at its tip (FloWire; EndoSonics, Rancho Cordova, California). The validation of this Doppler guidewire has been described previously (11).

Coronary flow velocity reserve (CFVR) distal to the stenosis was determined by dividing hyperemic peak flow velocity averaged over two cardiac cycles (APV, cm/s) by APV at rest. Hyperemia was induced using an IC bolus of 18 μg adenosine for the left and 12 μg adenosine for the right coronary artery (20).

The velocity-derived index of collateral flow to the balloon-occluded vascular region relative to normal resting flow during vessel patency (CFIv, no unit) was determined as the ratio of flow velocity time integral distal to the occluded stenosis (Vioccl, cm) divided by that obtained at an identical location after PTCA (i.e., not occluded, Viø-occl, cm): Vioccl/Viø-occl (online measurements; Figure 1 and Figure 2) (17). Vi represents the integral of flow velocities over time during a cardiac cycle (averaged over two cycles). In patients revealing temporally shifted bidirectional velocity signals, antegrade and retrograde Vi were added to obtain Vioccl.

IC pressure measurements
A 0.014 in. fiberoptic pressure monitoring guidewire (Pressureguide; Radi Medical, Uppsala, Sweden) was set at 0, calibrated, advanced through the guiding catheter and positioned distal to the stenosis to be dilated 21 and 22. The IC pressure-derived CFIp (no unit) was determined by simultaneous measurement of mean aortic pressure (Pao, mm Hg, obtained from the angioplasty guiding catheter) and the distal coronary artery pressure during balloon occlusion (Poccl, mm Hg; Figure 1 and Figure 2). Central venous pressure was estimated to be equal to 5 mm Hg. Pressure-derived collateral flow index was calculated as (Poccl-CVP) divided by (Pao-CVP) (18) (Fig. 1). Pressure-derived collateral flow index expresses collateral flow relative to normal flow through the patent vessel, an index that conceptually corresponds to CFIv.

Intracoronary distal flow velocity and pressure measurements during balloon occlusion and vessel patency after PTCA were performed simultaneously.