Non-invasive peripheral vascular function, incident cardiovascular disease, and mortality in the general population.

AIMS: Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of non-invasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality. METHODS AND RESULTS: In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N=12 599) and fingertip peripheral arterial tonometry (N=11 125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased event-free survival with higher mean brachial artery diameter and baseline pulse amplitude and better survival with higher mean flow-mediated dilatation and peripheral arterial tonometry ratio (all Plog rank <0.05). In multivariable-adjusted Cox regression analyses only baseline pulse amplitude was inversely related to mortality [hazard ratio (HR) per standard deviation increase, 0.86, 95% confidence interval (95% CI), 0.79-0.94; P=0.0009]. After exclusion of individuals with prevalent CVD the association was no longer statistically significant in multivariable-adjusted models (HR 0.91, 95% CI 0.81-1.02; P=0.11). None of the vascular variables substantially increased the C-index of a model comprising clinical risk factors. CONCLUSIONS: In our cohort, non-invasive measures of peripheral vascular structure and function did not reveal clinically relevant associations with incident CVD or mortality. Whether determination of pulse amplitude by peripheral arterial tonometry improves clinical decision-making in primary prevention needs to be demonstrated.

Cardiovascular profiling in the diabetic continuum: results from the population-based Gutenberg Health Study.

AIMS: To assess the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in the general population and to investigate the associated cardiovascular burden and clinical outcome. METHODS AND RESULTS: The study sample comprised 15,010 individuals aged 35-74 years of the population-based Gutenberg Health Study. Subjects were classified into euglycaemia, prediabetes and T2DM according to clinical and metabolic (HbA1c) information. The prevalence of prediabetes was 9.5% (n = 1415) and of T2DM 8.9% (n = 1316). Prediabetes and T2DM showed a significantly increased prevalence ratio (PR) for age, obesity, active smoking, dyslipidemia, and arterial hypertension compared to euglycaemia (for all, P < 0.0001). In a robust Poisson regression analysis, prediabetes was established as an independent predictor of clinically-prevalent cardiovascular disease (PRprediabetes 1.20, 95% CI 1.07-1.35, P = 0.002) and represented as a risk factor for asymptomatic cardiovascular organ damage independent of traditional risk factors (PR 1.04, 95% CI 1.01-1.08, P = 0.025). Prediabetes was associated with a 1.5-fold increased 10-year risk for cardiovascular disease compared to euglycaemia. In Cox regression analysis, prediabetes (HR 2.10, 95% CI 1.76-2.51, P < 0.0001) and T2DM (HR 4.28, 95% CI 3.73-4.92, P < 0.0001) indicated for an increased risk of death. After adjustment for age, sex and traditional cardiovascular risk factors, only T2DM (HR 1.89, 95% CI 1.63-2.20, P < 0.0001) remained independently associated with increased all-cause mortality. CONCLUSION: Besides T2DM, also prediabetes inherits a significant cardiovascular burden, which translates into poor clinical outcome and indicates the need for new concepts regarding the prevention of cardiometabolic disorders.

Choroidal thickness is associated with cardiovascular risk factors and cardiac health: the Gutenberg Health Study.

BACKGROUND: Choroidal thickness is associated with several cardiovascular parameters in case-control studies including patients with manifest disease. So far, it was unclear whether underlying cardiovascular risk factors or the continuum of heart failure may lead to alterations of the choroid. Therefore, our hypothesis was to test in a population-based study, whether choroidal thickness is associated with cardiovascular risk factors and heart disease. METHODS: A population-based cross-sectional study was carried out in Germany. A comprehensive medical examination including assessment of cardiovascular risk factors, echocardiography and ophthalmological examinations with spectral-domain optical coherence tomography of the choroid was performed. Subfoveal choroidal thickness as well as left ventricular ejection fraction (LVEF) and a surrogate marker for left ventricular end-diastolic pressure (E/e') were measured. Linear regression analyses were carried out to determine the relationship between subfoveal choroidal thickness and age, sex, body mass index, systolic blood pressure, dyslipidemia, HbA1c level, hematocrit, estimated glomerular filtration rate (eGFR), LVEF, E/e' and left ventricular mass index adjusted for ocular parameters. RESULTS: 1.742 subjects (48% females) with a mean age 59.3 ± 10.6 years were included in this study. Mean subfoveal thickness was 252 ± 77 µm (right eyes) and 255 ± 77 µm (left eyes). Unadjusted linear regression analysis revealed that subfoveal choroidal thickness is associated with sex, age, systolic blood pressure, hematocrit, eGFR, left ventricular end-diastolic pressure, left ventricular mass index (all p < 0.001) and dyslipidemia (p = 0.009). Adjusted linear regression only revealed age as associated parameter (p < 0.001). CONCLUSIONS: We did find evidence for an association between subfoveal choroidal thickness and cardiovascular risk factors which was mediated by aging.

Left ventricular geometry and function in early repolarization: results from the population-based Gutenberg Health Study.

AIMS: The electrocardiographic pattern of early repolarization (ER) is related to increased cardiac mortality in the general population. The pathophysiological basis of ER is largely unknown. We investigated the association of echocardiographic structural and functional parameters of the left ventricle with the presence of ER in the community. METHODS AND RESULTS: The presence of ER (ER+) was assessed in 13,878 participants (mean age 54.6 years, 51.1% women) of the Gutenberg Health Study and related to left ventricular structure and function derived from standard echocardiography. The prevalence of ER was 5.0% (694/13,878), with higher prevalence in men than women (6.6% vs. 3.5%, p < 0.001). In men baseline characteristics differed including a lower BMI and a lower heart rate in ER+ individuals, whereas in women there were only minor differences. Multivariable-adjusted logistic regression analysis in men showed an association of ER with smaller diameters (left-ventricular end-diastolic diameter: OR 0.77 95% CI 0.69-0.86, p < 0.001; left-ventricular end-systolic diameter: OR 0.86 95% CI 0.78-0.95, p = 0.0035), and lower left-ventricular end-diastolic and end-systolic volume (OR 0.72 95% CI 0.65, 0.80, p < 0.001 and OR 0.80 95% CI 0.72, 0.89, p < 0.001). In women, the associations of ER with left ventricular diameters and volumes showed a similar direction, but were not as pronounced. CONCLUSION: In the community, the ER pattern predominantly occurs in men with a low heart rate and a slender habit. Furthermore, ER is not associated with higher left ventricular mass or size but rather with smaller left ventricular diameters and volumes with a regular systolic and diastolic function. Patterns were comparable in women, but less strong.

Cross-Sectional Associations between Homoarginine, Intermediate Phenotypes, and Atrial Fibrillation in the Community-The Gutenberg Health Study.

Homoarginine has come into the focus of interest as a biomarker for cardiovascular disease. Atrial fibrillation (AF) causes a substantial increase in morbidity and mortality. Whether circulating homoarginine is associated with occurrence or persistence of AF and may serve as a new predictive biomarker remains unknown. We measured plasma levels of homoarginine in the population-based Gutenberg health study (3761 patients included, of them 51.7% males), mean age 55.6 ± 10.9 years-old. Associations between homoarginine and intermediate electrocardiographic and echocardiographic phenotypes and manifest AF were examined. Patients with AF (124 patients, of them 73.4% males) had a mean age 64.8 ± 8.6 years-old compared to a mean age of 55.3 ± 10.9 in the population without AF (p-value < 0.001) and showed a less beneficial risk factor profile. The median homoarginine levels in individuals with and without AF were 1.9 µmol/L (interquartile range (IQR) 1.5⁻2.5) and 2.0 µmol/L (IQR 1.5⁻2.5), respectively, p = 0.56. In multivariable-adjusted regression analyses homoarginine was not statistically significantly related to electrocardiographic variables. Among echocardiographic variables beta per standard deviation increase was -0.12 (95% confidence interval (CI) -0.23⁻(-0.02); p = 0.024) for left atrial area and -0.01 (95% CI -0.02⁻(-0.003); p = 0.013) for E/A ratio. The odds ratio between homoarginine and AF was 0.91 (95% CI 0.70⁻1.16; p = 0.45). In our large, population-based cross-sectional study, we did not find statistically significant correlations between lower homoarginine levels and occurrence or persistence of AF or most standard electrocardiographic phenotypes, but some moderate inverse associations with echocardiographic left atrial size and E/A. Homoarginine may not represent a strong biomarker to identify individuals at increased risk for AF. Further investigations will be needed to elucidate the role of homoarginine and cardiac function.

Relationship and prognostic value of microvascular obstruction and infarct size in ST-elevation myocardial infarction as visualized by magnetic resonance imaging.

BACKGROUND: Both infarct size and microvascular obstruction (MO) assessed by cardiac magnetic resonance imaging (CMR) are known to be predictors for adverse clinical outcome after ST-elevation myocardial infarction (STEMI). We hypothesized that a ratio of MO and infarct size (MO/infarct size) might be an even stronger predictor for outcome after STEMI, which has not been investigated yet. METHODS: STEMI patients reperfused by primary angioplasty (n = 438) within 12 h after symptom onset underwent contrast-enhanced CMR at a median of 3 days (interquartile range [IQR] 2;4) after the index event. MO and infarct size were measured 15 min after intravenous gadolinium injection. Follow-up was conducted after 19 months (IQR 10;27). The primary end point was defined as a composite of death, non-fatal myocardial reinfarction and congestive heart failure (major adverse cardiac events [MACE]). RESULTS: The extent of MO was only weakly correlated with infarct size (r = 0.21, p < 0.001). In a first multivariate analysis including extent of MO, infarct size, ejection fraction, end-systolic and end-diastolic volume, the extent of MO was independently associated with MACE (hazard ratio [HR] 1.03, 95%CI 1.02­1.05, p < 0.001). In a second multivariate analysis including MO/infarct size on top of the extent of MO, infarct size, ejection fraction, end-systolic and end-diastolic volume, MO/infarct size was identified as the strongest independent predictor for MACE (HR 2.22 [95%CI 1.60­3.08, p < 0.001]). CONCLUSIONS: In contrast to infarct size, MO is associated with adverse clinical outcome after STEMI even after adjustment for other CMR parameters. However, MO/infarct size is a more powerful predictor for long-term outcome after STEMI than either parameter alone.

Randomized comparison of pre-hospital-initiated facilitated percutaneous coronary intervention versus primary percutaneous coronary intervention in acute myocardial infarction very early after symptom onset: the LIPSIA-STEMI trial (Leipzig immediate prehospital facilitated angioplasty in ST-segment myocardial infarction).

OBJECTIVES: This multicenter trial sought to assess the merits of facilitated percutaneous coronary intervention (PCI) versus primary PCI in an ST-segment elevation myocardial infarction (STEMI) network with long transfer distances in patients presenting early after symptom onset. BACKGROUND: Facilitated PCI with fibrinolysis might be beneficial in specific high-risk STEMI situations to prevent myocardial necrosis expansion. METHODS: Patients with STEMI (<3 h after symptom onset) were randomized to either pre-hospital-initiated facilitated PCI using tenecteplase (Group A; n = 81) or primary PCI (Group B; n = 81) plus optimal antithrombotic comedication. The primary endpoint was infarct size assessed by delayed-enhancement magnetic resonance imaging. Secondary endpoints were microvascular obstruction and myocardial salvage, early ST-segment resolution, and a composite of death, repeated myocardial infarctions, and congestive heart failure within 30 days. RESULTS: The median time from symptom onset to randomization was 64 min (interquartile range [IQR]: 42 to 103 min) in Group A versus 55 min in Group B (IQR: 27 to 91 min; p = 0.26). Despite better pre-interventional TIMI (Thrombolysis In Myocardial Infarction) flow in Group A (71% vs. 35% TIMI flow grade 2 or 3; p < 0.001), the infarct size tended to be worse in Group A versus Group B (17.9% of left ventricle [IQR: 8.4% to 35.0%] vs. 13.7% [IQR: 7.5% to 24.0%]; p = 0.10). There was also a strong trend toward more early and late microvascular obstruction, (p = 0.06 and 0.09) and no difference in ST-segment resolution (p = 0.26). The combined clinical endpoint showed a trend toward higher event rates in Group A (19.8% vs. 13.6%; p = 0.13, relative risk: 0.52, 95% confidence interval: 0.23 to 1.18). CONCLUSIONS: In STEMI patients presenting early after symptom onset with relatively long transfer times, a fibrinolytic-based facilitated PCI approach with optimal antiplatelet comedication does not offer a benefit over primary PCI with respect to infarct size and tissue perfusion. ([LIPSIA-STEMI] The Leipzig Immediate Prehospital Facilitated Angioplasty in ST-Segment Myocardial Infarction; NCT00359918).

Impact of early vs. late microvascular obstruction assessed by magnetic resonance imaging on long-term outcome after ST-elevation myocardial infarction: a comparison with traditional prognostic markers.

AIMS: Early and late microvascular obstruction (MO) assessed by magnetic resonance imaging (MRI) are prognostic markers for combined clinical endpoints after ST-elevation myocardial infarction (STEMI). However, there are only limited data for hard endpoints and no consensus exists which of the two best predicts clinical outcome. Furthermore, it is unclear whether the assessment of MO by MRI adds incremental prognostic information independent of traditional outcome markers. METHODS AND RESULTS: STEMI patients reperfused by primary angioplasty (n = 438) < 12 h after symptom onset underwent MRI at a median of 3 days after the index event. Microvascular obstruction was measured 1 and 15 min after gadolinium injection (early and late MO). Clinical follow-up was conducted after a median of 19 months. The primary endpoint was defined as a composite of death, non-fatal myocardial re-infarction, and congestive heart failure. In contrast to the presence and extent of early MO, the presence and extent of late MO were independently associated with the composite primary endpoint in the multivariable Cox regression analysis adjusting for post-percutaneous coronary intervention TIMI-flow, ST-resolution, TIMI-risk score, ejection fraction, and infarct size. The presence of late MO was identified as the strongest independent predictor for the occurrence of the composite endpoint (hazard ratio 4.23, 95%CI 1.73-10.34, P = 0.002). Furthermore, the presence and extent of late MO provided an incremental prognostic value above the traditional prognostic markers. CONCLUSION: In contrast to early MO, the presence and extent of late MO are strong independent prognosticators after STEMI. www.ClinicalTrials.gov: NCT00299377.