Guideline-Recommended Time Less Than 90 Minutes From ECG to Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction Is Associated with Major Survival Benefits, Especially in Octogenarians: A Contemporary Report in 11 226 Patients from NORIC.

Background Using contemporary data from NORIC (Norwegian Registry of Invasive Cardiology) we investigated the predictive value of patient age and time from ECG diagnosis to sheath insertion (ECG-2-sheath) in primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction (STEMI). Methods and Results Data from 11 226 patients collected from all centers offering 24/7/365 primary percutaneous coronary intervention service were explored. For patients aged <80 years the mortality rates were 5.6% and 7.6% at 30 days and 1 year, respectively. For octogenarians the corresponding rates were 15.0% and 24.2%. The Cox hazard ratio was 2.02 (1.93-2.11, P value <0.0001) per 10 years of patient age. Time from ECG-2-sheath was significantly associated with mortality with a 3.6% increase per 30 minutes of time. Using achievement of time goal <90 minutes in patients aged >80 years and mortality at 30 days, mortality was 10.5% and 17.7% for <90 or ≥90 minutes, respectively. The number needed to prevent 1 death was 39 in the whole population and 14 in the elderly. Restricted mean survival gains during median 938 days of follow-up in patients with ECG-2-sheath time <90 minutes were 24 and 76 days for patients aged <80 and ≥80 years, respectively. Conclusions Time from ECG-diagnosis to sheath insertion is strongly correlated with mortality. This applies especially to octogenarians who derive the most in terms of absolute mortality reduction. Registration URL: https://helsedata.no/en/forvaltere/norwegian-institute-of-public-health/norwegian-registry-of-invasive-cardiology/.

The Full Revasc (Ffr-gUidance for compLete non-cuLprit REVASCularization) Registry-based randomized clinical trial.

BACKGROUND: Complete revascularization in ST elevation myocardial infarction (STEMI) patients with multivessel disease has resulted in reduction in composite clinical endpoints in medium sized trials. Only one trial showed an effect on hard clinical endpoints, but the revascularization procedure was guided by angiographic evaluation of stenosis severity. Consequently, it is not clear how Fractional Flow Reserve (FFR)-guided percutaneous coronary intervention (PCI) affects hard clinical endpoints in STEMI. METHODS AND RESULTS: The Ffr-gUidance for compLete non-cuLprit REVASCularization (FULL REVASC) - is a pragmatic, multicenter, international, registry-based randomized clinical trial designed to evaluate whether a strategy of FFR-guided complete revascularization of non-culprit lesions, reduces the combined primary endpoint of total mortality, non-fatal MI and unplanned revascularization. 1,545 patients were randomized to receive FFR-guided PCI during the index hospitalization or initial conservative management of non-culprit lesions. We found that in angiographically severe non-culprit lesions of 90-99% severity, 1 in 5 of these lesions were re-classified as non-flow limiting by FFR. Considering lesions of intermediate severity (70%-89%), half were re-classified as non-flow limiting by FFR. The study is event driven for an estimated follow-up of at least 2.75 years to detect a 9.9%/year>7.425%/year difference (HR = 0.74 at 80% power (α = .05)) for the combined primary endpoint. CONCLUSION: This large randomized clinical trial is designed and powered to evaluate the effect of complete revascularization with FFR-guided PCI during index hospitalization on total mortality, non-fatal MI and unplanned revascularization following primary PCI in STEMI patients with multivessel disease. Enrollment completed in September 2019 and follow-up is ongoing.

Long-Term Survival after Invasive or Conservative Strategy in Elderly Patients with non-ST-Elevation Myocardial Infarction: A Prospective Cohort Study.

BACKGROUND: The optimal management of elderly patients with non-ST-segment elevation myocardial infarction (NSTEMI) is still discussed. We aimed to study short- and long-term survival in NSTEMI patients ≥75 years managed with an invasive or a conservative strategy. METHODS: NSTEMI patients admitted to Oslo University Hospital Ulleval during 2005-2011 were included consecutively in a prospective registry. Vital status until December 31, 2013, was obtained from the Norwegian Cause of Death Registry. Patients ≥75 years were identified, and 30-day and 7-year survival were analyzed. Logistic- and Cox regression was used to estimate OR and hazard ratio (HR) for death in the invasive versus conservative group, adjusting for registered confounders. RESULTS: There were 2,064 NSTEMI patients ≥75 years (48.2% women); 1,200 (58.1%) were treated with an invasive strategy, and were younger, more likely to be male and previously revascularized compared to 864 (41.9%) patients treated conservatively (p < 0.0001 for all). Survival at 30-day was 94.9% in the invasive and 76.6% in the conservative group. For 30-day survivors, 7-year survival was 47.4% (95% CI 42.9-51.8) and 11.6% (95% CI 8.3-15.6), respectively. After multivariate adjustment, an invasive strategy was associated with lower long-term risk (adjusted HR [aHR] 0.49 [95% CI 0.41-0.59]). Actual revascularization was associated with lower risk of long-term mortality compared to angiography only (aHRPCI 0.73 [95% CI 0.59-0.90], aHRCABG 0.43 [95% CI 0.28-0.65]). CONCLUSION: In this real-life cohort of NSTEMI patients ≥75 years, 30-day survival was 95%, and 7-year survival was 47% with an invasive strategy. Revascularized patients had a superior long-term prognosis. With a conservative strategy, short- and long-term survival was lower, probably due to selection bias and unmeasured confounding.

Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease.

BACKGROUND: Limited data are available on the long-term effects of contemporary drug-eluting stents versus contemporary bare-metal stents on rates of death, myocardial infarction, repeat revascularization, and stent thrombosis and on quality of life. METHODS: We randomly assigned 9013 patients who had stable or unstable coronary artery disease to undergo percutaneous coronary intervention (PCI) with the implantation of either contemporary drug-eluting stents or bare-metal stents. In the group receiving drug-eluting stents, 96% of the patients received either everolimus- or zotarolimus-eluting stents. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularization, stent thrombosis, and quality of life. RESULTS: At 6 years, the rates of the primary outcome were 16.6% in the group receiving drug-eluting stents and 17.1% in the group receiving bare-metal stents (hazard ratio, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.66). There were no significant between-group differences in the components of the primary outcome. The 6-year rates of any repeat revascularization were 16.5% in the group receiving drug-eluting stents and 19.8% in the group receiving bare-metal stents (hazard ratio, 0.76; 95% CI, 0.69 to 0.85; P<0.001); the rates of definite stent thrombosis were 0.8% and 1.2%, respectively (P=0.0498). Quality-of-life measures did not differ significantly between the two groups. CONCLUSIONS: In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug-eluting stents. (Funded by the Norwegian Research Council and others; NORSTENT ClinicalTrials.gov number, NCT00811772 .).

Long-term survival in octogenarians and older patients with ST-elevation myocardial infarction in the era of primary angioplasty: A prospective cohort study.

AIM: We aimed to study in-hospital mortality and long-term survival in elderly compared to younger patients with ST-segment elevation myocardial infarction (STEMI) in the era of primary angioplasty. METHODS AND RESULTS: This was a prospective cohort study. All consecutive STEMI-patients admitted to our hospital between September 2005-December 2011 were included in a local registry. Predefined variables were registered during hospital admission. Vital status was obtained from the Norwegian Cause of Death Registry with censoring date 31 December 2011. Adjusted effects of age ⩾80 years on in-hospital- and long-term mortality were determined using propensity score analysis. Of 4525 registered STEMI patients, 600 (13%) were octogenarians or older. In-hospital mortality was 17% in patients ⩾80 years and 4% in patients <80 years. In invasively treated patients (83% of patients ⩾80 years; 98% of patients <80 years), in-hospital mortality was 13% and 3.4%, respectively. Median follow-up time was 2.5 years. Three-year cumulative survival was 52% in patients ⩾80 years vs 89% in patients <80 years. In invasively treated patients ⩾80 years, three-year survival was 58%. The adjusted odds ratio of in-hospital mortality was 2.61 (1.94-3.52) and adjusted incidence rate ratio of long-term mortality was 4.07 (3.43-4.84) in very elderly compared to younger patients. CONCLUSION: Short-term prognosis was acceptable in very elderly STEMI patients, especially in the invasively treated subgroup. However, only 52% of STEMI patients ⩾80 years were alive after three years of follow-up. Very elderly patients had 2.6 times higher risk of in-hospital mortality and 4.1 times the risk of not surviving during long-term follow-up compared to patients <80 years, after adjustment for confounding factors and selection bias.

Post-Resuscitation ECG for Selection of Patients for Immediate Coronary Angiography in Out-of-Hospital Cardiac Arrest.

BACKGROUND: We aimed to investigate coronary angiographic findings in unselected out-of-hospital cardiac arrest patients referred to immediate coronary angiography (ICA) irrespective of their first postresuscitation ECG and to determine whether this ECG is useful to select patients with no need of ICA. METHODS AND RESULTS: All resuscitated patients admitted after out-of-hospital cardiac arrest without a clear noncardiac cause underwent ICA. Patients were retrospectively grouped according to the postresuscitation ECG blinded for ICA results: (1) ST elevation or presumably new left bundle branch block, (2) other ECG signs indicating myocardial ischemia, and (3) no ECG signs indicating myocardial ischemia. All coronary angiograms were reevaluated blinded for postresuscitation ECGs. Two hundred and ten patients were included with mean age 62±12 years. Six-months survival with good neurological outcome was 54%. Reduced Thrombolysis in Myocardial Infarction flow (0-2) was found in 55%, 34%, and 18% and a ≥90% coronary stenosis was present in 25%, 27%, and 19% of patients in group 1, 2, and 3, respectively. An acute coronary occlusion was found in 11% of patients in group 3. ST elevation/left bundle branch block identified patients with reduced Thrombolysis in Myocardial Infarction (0-2) flow with 70% sensitivity and 62% specificity. Among patients with initial nonshockable rhythms (24%), 32% had significantly reduced Thrombolysis in Myocardial Infarction flow. CONCLUSIONS: Initial ECG findings are not reliable in detecting patients with an indication for ICA after experiencing a cardiac arrest. Even in the absence of ECG changes indicating myocardial ischemia, an acute culprit lesion may be present and patients may benefit from emergent revascularization. CLINICAL TRIAL REGISTRATIONURL: http://www.clinicaltrials.gov. Unique identifier: NCT01239420.

Family history of hypertension and serum triglycerides predict future insulin sensitivity: a 17-year follow-up study of young men.

OBJECTIVE: Low insulin sensitivity is closely related to both cardiovascular diseases and diabetes development. Still, correlates of insulin sensitivity have mainly been examined in cross-sectional studies. As far as we are aware, the longitudinal stability of insulin sensitivity in young men is largely unknown. We aimed for the first time to examine both the stability (tracking) and longitudinal predictors of future insulin sensitivity in healthy young men with and without a family history of diabetes or hypertension. METHODS: We performed a 17-year follow-up study of a cohort of 100 healthy young men. Cardiovascular risk markers, including insulin sensitivity measured by the gold standard method--hyperinsulinaemic isoglycaemic glucose clamp--were examined both at baseline and at follow-up. RESULTS: Baseline insulin sensitivity showed no significant correlation with insulin sensitivity at follow-up, whereas all other measured cardiovascular risk markers had significant correlation (tracking coefficients 0.4-0.7). In multiple regression analyses, family history of hypertension and baseline triglycerides remained the negative predictors of future insulin sensitivity. This was driven by the strong correlations in men with family history of diabetes. CONCLUSION: Our data suggest that clamp-derived insulin sensitivity is not a stable feature in young men, and that family history of hypertension and baseline triglycerides were associated with future insulin sensitivity, especially in men with a family history of diabetes, and irrespective of blood pressure status 17 years earlier. These findings provide further insight into the development of insulin sensitivity and related diseases.

High screening blood pressure at young age predicts future masked hypertension: A 17 year follow-up study.

OBJECTIVE: Approximately 10-20% of the general population have masked hypertension. However, how best to identify affected individuals is uncertain, and what predicts future masked hypertension is largely unknown. This study aimed to identify longitudinal predictors of masked hypertension. METHODS: A long-term follow-up study of 100 healthy young men who had normal (n = 28) or high (n = 72) screening blood pressure (BP) at the compulsory military draft was carried out. They were examined in a detailed and highly standardized way for cardiovascular risk markers at baseline and at follow-up after a mean of 17.4 years. RESULTS: At follow-up, 40% had masked hypertension. Participants with high screening BP had a 4.8 times higher likelihood of having masked hypertension at follow-up compared to men with low screening BP (odds ratio 4.8, 95% confidence interval 1.7-13.5, p = 0.003). Furthermore, only 25% of the men with masked hypertension had high normal office BP at follow-up, and the remaining 75% would, according to guidelines, not be recommended ambulatory BP measurements, and thus go undiagnosed. CONCLUSION: Our data suggest that high screening BP at a young age is an important predictor of future masked hypertension in young men, and that BP measurement according to guidelines is insufficient to uncover masked hypertension.

Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension.

We aimed to investigate for the first time the blood pressure (BP)-lowering effect of renal sympathetic denervation (RDN) versus clinically adjusted drug treatment in true treatment-resistant hypertension (TRH) after excluding patients with confounding poor drug adherence. Patients with apparent TRH (n=65) were referred for RDN, and those with secondary and spurious hypertension (n=26) were excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic. In addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP and were excluded. Patients with true TRH were randomized and underwent RDN (n=9) performed with Symplicity Catheter System versus clinically adjusted drug treatment (n=10). The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg (±SD) at baseline to 132±10/77±8 mm Hg at 6 months (P<0.0005 and P=0.02, SBP and diastolic BP, respectively) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg (P=0.42 and P=0.48, SBP and diastolic BP, respectively). SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months (P=0.002 and P=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (P=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516.

[Renal sympathetic denervation in treatment-resistant hypertension]. / Renal sympatisk denervering ved terapiresistent hypertensjon.

BACKGROUND: Renal denervation (RDN) has been introduced as a potential new treatment for patients with treatment-resistant hypertension, defined as a blood pressure above 140/90 mm Hg despite treatment with at least three antihypertensive drugs. We present an overview of this type of treatment, describe the method and discuss its possible future uses. METHOD: The review is based on a discretionary selection of relevant articles from our archive, our own experience and a literature search in PubMed. RESULTS: The use of RDN for treatment-resistant hypertension is based on a single randomised study with a total of 104 patients, in which the intervention group experienced a fall in blood pressure of 32/12 mm Hg, while blood pressure in the control group remained unchanged. More than 16,000 patients, particularly in Germany, have been treated on this basis. In the USA, data from a larger randomised study (n = 530) that includes sham surgery are awaited before any decision is made on whether to approve the method for use. INTERPRETATION: Before RDN can become recommended treatment in Norway, more evidence is required that the method lowers blood pressure, and that this reduces morbidity and mortality.

Renal sympathetic denervation in patients with treatment-resistant hypertension after witnessed intake of medication before qualifying ambulatory blood pressure.

It is unknown whether the decline in blood pressure (BP) after renal denervation (RDN) is caused by denervation itself or concomitantly improved drug adherence. We aimed to investigate the BP lowering effect of RDN in true treatment-resistant hypertension by excluding patients with poor drug adherence. Patients with resistant hypertension (n=18) were referred for a thorough clinical and laboratory work-up. Treatment-resistant hypertension was defined as office systolic BP>140 mm Hg, despite maximally tolerated doses of ≥ 3 antihypertensive drugs, including a diuretic. In addition, ambulatory daytime systolic BP>135 mm Hg was required after witnessed intake of antihypertensive drugs to qualify. RDN (n=6) was performed with Symplicity Catheter System. The mean office and ambulatory BPs remained unchanged at 1, 3, and 6 months in the 6 patients, whereas there was no known change in antihypertensive medication. Two patients, however, had a fall in both office and ambulatory BPs. Our findings question whether BP falls in response to RDN in patients with true treatment-resistant hypertension. Additional research must aim to verify potential BP lowering effect and identify a priori responders to RDN before this invasive method can routinely be applied to patients with drug-resistant hypertension. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516.

Intravascular ultrasound assessed incomplete stent apposition and stent fracture in stent thrombosis after bare metal versus drug-eluting stent treatment the Nordic Intravascular Ultrasound Study (NIVUS).

BACKGROUND: This prospective multicenter registry used intravascular ultrasound (IVUS) in patients with definite stent thrombosis (ST) to compare rates of incomplete stent apposition (ISA), stent fracture and stent expansion in patients treated with drug-eluting (DES) versus bare metal (BMS) stents. ST is a rare, but potential life threatening event after coronary stent implantation. The etiology seems to be multifactorial. METHODS: 124 patients with definite ST were assessed by IVUS during the acute ST event. The study was conducted in 15 high-volume percutaneous coronary intervention -centers in the Nordic-Baltic countries. RESULTS: In early or late ST there were no differences in ISA between DES and BMS. In very late ST, ISA was a more frequent finding in DES than in BMS (52% vs.16%; p=0.005) and the maximum ISA area was larger in DES compared to BMS (1.1 ± 2.3mm(2) vs. 0.1 ± 0.5mm(2); p=0.004). Further, ISA was more prevalent in sirolimus-eluting than in paclitaxel-eluting stents (58% vs. 37%; p=0.02). Stent fractures were found both in DES (16%) and BMS (24%); p=0.28, and not related to time of stent thrombosis occurrence. For stents with nominal diameters ≥ 2.75 mm, 38% of the DES and 22% of the BMS had a minimum stent area of less than 5mm(2); p=0.14. CONCLUSIONS: Very late stent thrombosis was more prevalent and associated with more extensive ISA in DES than in BMS treated patients. Stent fracture was a common finding in ST after DES and BMS implantation.

Cardiac magnetic resonance visualizes acute and chronic myocardial injuries in myocarditis.

Our objective was to evaluate the ability of CMR to visualize myocardial injuries over the course of myocarditis. We studied 42 patients (39 males, 3 females; age 37 ± 14 years) with myocarditis during the acute phase and after 12 ± 9 months. CMR included function analyses, T2-weighted imaging (T2 ratio), T1-weighted imaging before and after i.v. gadolinium injection (global relative enhancement; gRE), and late gadolinium enhancement (LGE). In the acute phase, the T2 ratio was elevated in 57%, gRE in 31%, and LGE was present in 64% of the patients. In 32 patients (76%) were any two (or more) out of three sequences abnormal. At follow-up, there was an increase in ejection fraction (57.4 ± 11.9% vs. 61.4 ± 7.6; P < 0.05) while both T2 ratio (2.04 ± 0.32 vs. 1.70 ± 0.28; P < 0.001) and gRE (4.07 ± 1.63 vs. 3.11 ± 1.22; P < 0.05) significantly decreased. The LGE persisted in 10 patients. Dilated cardiomyopathy was present in 3 patients and 4 patients received a defibrillator or a pacemaker. A comprehensive CMR approach is a useful tool to visualize myocardial tissue injuries over the course of myocarditis. CMR may help to differentiate acute from healed myocarditis, and add information for the differential diagnoses.

Takotsubo cardiomyopathy in acute coronary syndrome; clinical features and contribution of cardiac magnetic resonance during the acute and convalescent phase.

OBJECTIVES: Takotsubo cardiomyopathy (TTC) is a diagnostic entity that is increasingly being recognized. Data from cardiac magnetic resonance (CMR) imaging and its impact on differential diagnosis are limited. METHODS AND RESULTS: After 26 months, coronary angiography revealed normal coronary arteries and left ventriculography and/or echocardiography left ventricular dysfunction with apical ballooning in 20 patients with acute coronary syndrome (ACS). Four patients were excluded from CMR and in three patients an alternative diagnosis was revealed. Thirteen patients (all female; 60 ± 8 years) with TTC underwent a multisequential CMR, in which all showed myocardial oedema with an elevated T2 ratio in the apical region (2.4 ± 0.4; p < 0.001 vs. healthy controls), and five patients an elevated global relative enhancement (gRE; 3.7 ± 1.4; p < 0.05 vs. healthy controls). No late gadolinium enhancement (LGE) was detected on CMR. Follow-up after 132 ± 33 days showed a normalized left ventricular ejection fraction, myocardial mass, T2 ratio, and gRE in all patients. CONCLUSIONS: TTC is a small but definite group among patients with ACS and normal coronary arteries. CMR allows differentiating TTC from other causes such as myocarditis and cardiomyopathies, as well as to identify the transient increase of myocardial mass and resolution of myocardial oedema as the systolic dysfunction improves. Therefore, CMR might add valuable information for the differential diagnoses and therapeutic decision-making in patients with suspected TTC.

Chronic occlusion of the left main coronary artery: importance of collaterals.

Chronic occlusion of the left coronary artery is an infrequent finding in patients undergoing coronary angiography. These patients usually present symptoms of angina or heart failure. We describe a patient who was training regularly without cardiac symptoms until ventricular fibrillation suddenly occurred during a long-distance run. A chronic left main stem occlusion with well-developed right-to-left coronary collaterals was demonstrated by angiography. Up to this event, the collateral flow had been sufficient to allow physical exercise at a high performance level without symptoms. The patient later underwent coronary bypass surgery and recovered completely.

Arterial plasma vasopressin and aldosterone predict left ventricular mass in men who develop hypertension over 20 years.

Left ventricular (LV) hypertrophy is related to blood pressure level and neurohormonal factors. The authors previously demonstrated that arterial norepinephrine levels predict LV mass in middle-aged men who developed hypertension through 20 years. The aim of this 20-year prospective study was to investigate arterial vasopressin, aldosterone, and renin as long-term predictors of LV mass. Normotensives (n=17), subjects who developed hypertension (n=17), and sustained hypertensives (n=22) were compared at baseline (42 years) and at follow-up (62 years). There were no significant differences in baseline vasopressin, aldosterone, or renin levels. The group with sustained hypertension had more LV hypertrophy (P=.025) at follow-up. Among new hypertensives, multiple regression analysis demonstrated that baseline arterial vasopressin (beta-0.53; P=.041) and aldosterone (beta-0.56;P=.032) independently explained LV mass index (R(2)=0.85; P=.035). In conclusion, baseline arterial vasopressin and aldosterone, but not renin, appear to predict LV mass in middle-aged men who developed hypertension over a 20-year period.

Increased hematocrit before blood pressure in men who develop hypertension over 20 years.

We have previously demonstrated that neurohormonal activity can predict left ventricular (LV) mass in men who developed hypertension over 20 years. The aim of the study was to investigate early markers of cardiac and hemorheological changes at baseline in these men, i.e., before a rise in blood pressure. Fifty-six middle-aged men were followed for 20 years; 22 were sustained hypertensives, 17 developed hypertension, and 17 were sustained normotensives. They were compared at baseline (42 years) and follow-up (62 years). We investigated Cornell voltage product and Sokolow-Lyon voltage, hematocrit (Hct), and echocardiographic LV parameters. There was no sign of LV hypertrophy by electrocardiography (ECG) at baseline. Baseline Hct discriminated between the groups (P= .015) and correlated to diastolic blood pressure (DBP) at baseline (r = 0.37, P= .006) and follow-up (r = 0.31, P= .020). Regression analysis identified baseline Hct as an independent correlate of DBP in the cohort at baseline when they were untreated (beta = .33, P= .013, R(2) = 0.25), and of borderline significance at follow-up (beta = .26, P= .060, R(2) = 0.12) despite possible interference by antihypertensive drugs. Hct was elevated at baseline compatible with the hypothesis that pathogenic hemorheological processes could be activated at the outset and prior to cardiac changes in men who later develop hypertension.

Does long-term losartan- vs atenolol-based antihypertensive treatment influence collagen markers differently in hypertensive patients? A LIFE substudy.

BACKGROUND: The aim of this study was to investigate the effects of losartan- vs atenolol-based antihypertensive treatment on circulating collagen markers beyond the initial blood pressure (BP) reduction. METHODS: In 204 patients with hypertension and left ventricular (LV) hypertrophy we measured serum concentration of carboxy-terminal telopeptide of type I procollagen (ICTP), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), amino-terminal propeptide of type I procollagen (PINP) and LV mass by echocardiography at baseline and annually during 4 years of losartan- or atenolol-based antihypertensive treatment; 185 patients completed the study. RESULTS: Beyond the first year of treatment systolic and diastolic BP, LV mass index (LVMI) as well as collagen markers did not change significantly and were equal in the two treatment groups. Changes in PICP during first year of treatment were related to subsequent changes in LV mass index after 2 and 3 years of treatment (r=0.28 and r=0.29, both p<0.05) in patients randomized to losartan, but not atenolol. CONCLUSION: Long-term losartan- vs atenolol-based antihypertensive treatment did not influence collagen markers differently, making a BP-independent effect of losartan on collagen markers unlikely. However, initial reduction in circulating PICP may predict later regression of LV hypertrophy during losartan-based antihypertensive treatment.

Long-term effects of a losartan- compared with an atenolol-based treatment regimen on carotid artery plaque development in hypertensive patients with left ventricular hypertrophy: ICARUS, a LIFE substudy.

In the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study, there was a 25% risk reduction for stroke with angiotensin receptor blocker-based therapy (losartan) as compared with beta-blocker-based therapy (atenolol) despite comparable blood pressure reductions. This substudy examines treatment effects on the amount and density of atherosclerotic lesions in the common carotid arteries and the carotid bulb in 81 patients during 3 years of treatment. There were no statistically significant changes in the amount of carotid plaque in patients treated with losartan compared with an atenolol-based treatment program. A statistically nonsignificant increase in plaque density and index (average of plaque amount and density) was seen in the atenolol group compared with those treated with losartan. The small number of patients evaluated may have limited the power to detect a difference in outcome. The difference in carotid plaque index increase between the treatment groups during 3 years of treatment could not be statistically linked to specific treatments in the present substudy.