Treating arteries instead of risk factors: A paradigm change in management of atherosclerosis

Background and Purpose: Until recently, atherosclerosis was thought to be inexorably progressive. Beginning in 2001 and implemented in our vascular prevention clinics by 2003, we have been treating arteries rather than risk factors. We studied the proportion of patients with plaque progression vs regression before and after this change in paradigm. Methods: Carotid total plaque area was measured by ultrasound at baseline and during follow-up. Before 2003, patients were treated according to consensus guidelines. After 2003, patients with plaque progression were treated more intensively, with the explicit goal of halting plaque progression or achieving regression. RESULTS: Four thousand three-hundred seventy-eight patients had serial plaque measurements in a given year between 1997 and 2007; 47% were female. Mean age at time of referral was 60 (SD, 15); this increased steeply (from age 50 to 62 years over the first 5 years) as we focused on stroke prevention. The annual rate of plaque progression increased steeply as the clinic populations aged but then abruptly decreased after implementation of the new approach to therapy. Before 2003, approximately half the patients had plaque progression and ≈25% had regression; by 2005, this had reversed. Changes in plasma lipids show that the differences were attributable to plaque measurement, not simply more intensive therapy for all patients. By 2007, patients with progression had lower levels of low-density lipoprotein than those with regression. Conclusions: Treating arteries without measuring plaque would be like treating hypertension without measuring blood pressure. A clinical trial to test this approach is being designed. © 2010 American Heart Association, Inc

Decline in the severity of carotid atherosclerosis and associated risk factors from 2002 to 2014

Background and Purpose-Several recent studies suggest declining rates of carotid revascularization for patients with carotid stenosis. We investigated whether carotid atherosclerosis severity has declined in recent years. Methods-We used carotid ultrasound to evaluate stenosis and plaque area in 6039 patients presenting to vascular medicine clinics in 3 eras: 2002 to 2005, 2006 to 2009, and 2010 to 2014. Results-The total plaque area at the time of referral to the clinics declined by 24% between 2002 and 2014; the percentage of patients presenting with carotid stenosis \u3c60% declined by 29.9%, and the number presenting with \u3c80% stenosis declined by 36.4%. There were significant reductions in plasma lipids and blood pressure during the same interval. Conclusions-Atherosclerosis severity seems to be declining over time. Better treatment of risk factors in the community may be responsible

What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14 μmol/L

High levels of plasma homocyst(e)ine (H[e]) are associated with increased vascular risk. Treatment is being contemplated, but the level at which patients should be treated is not known. We compared the response of carotid plaque to vitamin therapy in patients with H(e) above and below 14 μmol/L, a level commonly regarded as high enough to warrant treatment. Two-dimensional B-mode ultrasound measurement of carotid plaque was used to assess the response to vitamin therapy with folic acid 2.5 mg, pyridoxine 25 mg, and cyanocobalamin 250 μg daily, in 101 patients with vascular disease (51 with initial plasma levels above, and 50 below 14 μmol/L). Among patients with plasma H(e) \u3e14 μmol/L, the rate of progression of plaque area was 0.21 ± 0.41 cm2/year before vitamin therapy, and -0.049 ± 0.24 cm2/year after vitamin therapy (P2 = .0001; paired t test). Among patients with levels \u3c14 μmol/L, the rate of progression of plaque was 0.13 ± 0.24 cm2/ year before vitamin therapy and -0.024 ± 0.29 cm2/year after vitamin therapy (P2 = .022, paired t test). The change in rate of progression was -0.15 ± .44 cm2/year below 14 μmol/L, and -0.265 ± 0.46 cm2/year above 14 μmol/L (P = 0.20). Vitamin therapy regresses carotid plaque in patients with H(e) levels both above and below 14 μmol/L. These observations support a causal relationship between homocyst(e)ine and atherosclerosis and, taken with epidemiologic evidence, suggest that in patients with vascular disease, the level to treat may be \u3c9 μmol/L. © 2000 American Journal of Hypertension, Ltd

Effects of eplerenone on resistance to antihypertensive medication in patients with primary or secondary hyperaldosteronism

Background and Objectives: Resistant hypertension is an important problem; nearly half of diagnosed hypertensives are not controlled to target blood pressure levels, and approximately 90% of strokes occur among patients with resistant hypertension. Primary aldosteronism accounts for approximately 20% of resistant hypertension, but the role of secondary hyperaldosteronism in resistant hypertension is seldom considered. We assessed the effects of eplerenone in patients with hypertension and either primary or secondary hyperaldosteronism. Methods: Patients with a history of resistant hypertension and a supine plasma aldosterone level ≥ 360 pmol/L were randomized to eplerenone versus placebo in a fully blinded study for one year. A medication intensity score was developed to assess the resistance of hypertension to medication (blood pressure × medication intensity). We assessed the effects of eplerenone on blood pressure and on resistance to concomitant medication. Results: Final results were available in 37 patients (19 on eplerenone and 18 on placebo). Resistance to medication, as assessed by the intensity of concomitant medication required to maintain blood pressure control, was markedly reduced by eplerenone: medication intensity scores declined by −0.50 ± 1.04 (SD) on placebo versus −2.11 ± 1.45 with eplerenone (P = 0.0001), the Systolic Resistance Score declined by −80.00 ± 122.93 on placebo versus −334.05 ± 21.73 on eplerenone (P = 0.0001), and the Diastolic Resistance Score increased by 1.28 ± 31.65 on placebo and declined by −40.74 ± 57.08 on eplerenone (P = 0.009). Conclusions: Eplerenone significantly reduced resistance to concomitant antihypertensive medication in both primary and secondary hyperaldosteronism

Carotid plaque area: A tool for targeting and evaluating vascular preventive therapy

Background and Purpose - Carotid plaque area measured by ultrasound (cross-sectional area of longitudinal views of all plaques seen) was studied as a way of identifying patients at increased risk of stroke, myocardial infarction, and vascular death. Methods - Patients from an atherosclerosis prevention clinic were followed up annually for up to 5 years (mean, 2.5±1.3 years) with baseline and follow-up measurements recorded. Plaque area progression (or regression) was defined as an increase (or decrease) of ≥0.05 cm2 from baseline. Results - Carotid plaque areas from 1686 patients were categorized into 4 quartile ranges: 0.00 to 0.11 cm2 (n=422), 0.12 to 0.45 cm2 (n=424), 0.46 to 1.18 cm2 (n=421), and 1.19 to 6.73 cm2 (n=419). The combined 5-year risk of stroke, myocardial infarction, and vascular death increased by quartile of plaque area: 5.6%, 10.7%, 13.9%, and 19.5%, respectively (P\u3c0.001) after adjustment for all baseline patient characteristics. A total of 1085 patients had ≥1 annual carotid plaque area measurements: 685 (63.1%) had carotid plaque progression, 306 (28.2%) had plaque regression, and 176 (16.2%) had no change in carotid plaque area over the period of follow-up. The 5-year adjusted risk of combined outcome was 9.4%, 7.6%, and 15.7% for patients with carotid plaque area regression, no change, and progression, respectively (P=0.003). Conclusions - Carotid plaque area and progression of plaque identified high-risk patients. Plaque measurement may be useful for targeting preventive therapy and evaluating new treatments and response to therapy and may improve cost-effectiveness of secondary preventive treatment

SPARKLE (Subtypes of ischaemic stroke classification system), Incorporating measurement of carotid plaque burden: A new validated tool for the classification of ischemic stroke subtypes

Background: Previous classification systems of acute ischemic stroke (Causative Classification System, CCS, of acute ischemic stroke, Trial of Org 10172 in Acute Stroke Treatment, TOAST) established the diagnosis of large artery disease (LAD) based on the presence or absence of carotid stenosis. However, carotid plaque burden is a stronger predictor of cardiovascular risk than stenosis. Our objective was to update definitions of ischemic stroke subtypes to improve the detection of LAD and to assess the validity and reliability of a new classification system: SPARKLE (Subtypes of Ischaemic Stroke Classification System). Methods: In a retrospective review of clinical research data, we compared three stroke subtype classifications: CCS, TOAST and SPARKLE. We analyzed a random sample of 275 patients presenting with minor stroke or transient ischemic attack (TIA) in an Urgent TIA Clinic in London, Ont., Canada, between 2002 and 2012. Results: There was substantial overall agreement between SPARKLE and CCS (κ = 0.75), with significant differences in the rate of detection of LAD, cardioembolic and undetermined causes of stroke or TIA. The inter-rater reliability of SPARKLE was substantial (κ = 0.76) and the intra-rater reliability was excellent (κ = 0.91). Conclusion: SPARKLE is a valid and reliable classification system, providing advantages compared to CCS and TOAST. The incorporation of plaque burden into the classification of LAD increases the proportion of cases attributable to LAD and reduces the proportion classified as being of \u27undetermined\u27 etiology. © 2014 S. Karger AG, Basel