M De Marco

Determinant factors for diagnostic delay in operable breast cancer patients

Randomized trials of mammographic screening have provided strong evidence that early diagnosis and treatment of breast cancer can reduce the specific mortality. Moreover, in a recent systematic review of published studies, delays of 3–6 months between symptom onset and treatment have been clearly found to be associated with lower survival rates for breast cancer patients. The aim of this study was to examine delays registered among breast cancer patients in southern Italy, in order to recognize their determining factors so as to provide women with a better opportunity for survival. The variables examined were age (<50, 50–64, ≥65 years), education (≤5, >5 school years); symptom status at first presentation (symptomatic or asymptomatic); date of first symptom presentation; date of first consultation with a health provider; the type of health provider consulted; tumour size and nodal status according to the pTNM system. Time intervals were categorized into: <1 month, 1–3 months and >3 months for patient and medical delay; 1–3 months, 3–6 months, >6 months for overall delay. Patient delay was associated with age and education: a higher risk was found for women of over 65 years age (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2–3.5) and with ≤5 years school attendance (OR 3.3, 95% CI 2.0–5.6). Medical delay was seen to be associated with the professional figure: significant differences were found between senologists (oncologists exclusively dedicated to breast cancer operation) and other specialists (OR 3.5, 95% CI 1.5–8.4). Young age and symptomatic presentation were found to be high risk factors. Concerning tumour size in overall delay, in cases where the tumour was >2 cm the OR was 2.4 (95% CI 1.5–3.7). Our study suggests that diagnostic delay can be reduced by providing more efficient training programmes for members of the medical profession and by producing educational training programmes targeted specifically at each age category (i.e. in older women more attention to education in prevention; in younger women correct information about mammography and specialized structures).

Primary prevention with statins and incident diabetes in hypertensive patients at high cardiovascular risk

BACKGROUND AND AIMS The ESC/ESH guidelines for arterial hypertension recommend using statins for patients with high cardiovascular (CV) risk for both secondary and primary prevention. A recent meta-analysis, combining previous studies on statins, concluded that they are associated with a 9% increased risk of incident type 2 diabetes mellitus (DM). There is no information on whether statins increase incidence of DM in primary prevention. METHOD AND RESULTS We evaluated risk of incident DM in relation to statin prescription in 4750 hypertensive, non-diabetic outpatients (age 58.57 ± 9.0 yrs, 42.3% women), from the CampaniaSalute Network, without chronic kidney disease more than grade 3, free of prevalent CV disease and with at least 12 months of follow-up. DM was defined according to ADA criteria. At the end of follow-up period (55.78 ± 42.5 months), 676 patients (14%) were on statins. These patients were older (62.54 ± 7.3 vs 57.91 ± 9.1 yrs; p < 0.0001), more often female (49% vs 41.2%; p = 0.0001), with higher initial total cholesterol (217.93 ± 44.3 vs 205.29 ± 36.6 mg/dl), non-HDL cholesterol (167.16 ± 44.5 vs 155.18 ± 36.7 mg/dl) and triglycerides (150.69 ± 85.2 vs 130.98 ± 72.0 mg/dl; all p < 0.0001) than patients no taking statins, without other differences in clinical and laboratory characteristics. At the end of follow-up, prevalence of DM was 18.1% among patients on statins and 7.2% among those without lipid-lowering therapy (p < 0.0001). However, incident DM was 10.2% in patients on statins and 8.7% in those free of statin therapy (NS). CONCLUSION In real-life outpatient environment, statin prescription for primary prevention is not associated with increased risk of incident DM.

Bochdaleck diaphragmatic hernia, complicated by an antenatal gastric perforation, presenting as a pneumothorax and a perforative peritonitis

The presentation of congenital diaphragmatic hernia (CDH) at birth may fall outside the typical features (cyanosis, tachypnea and respiratory failure), manifesting, instead, also with others pictures that make the diagnosis difficult or even impossible. We report a case of CDH presenting as a pneumothorax and a perforative peritonitis due to an antenatal gastric perforation.

Identification of phenotypes at risk of transition from diastolic hypertension to isolated systolic hypertension

Little is known about the potential progression of hypertensive patients towards isolated systolic hypertension (ISH) and about the phenotypes associated with the development of this condition. Aim of this study was to detect predictors of evolution towards ISH in patients with initial systolic–diastolic hypertension. We selected 7801 hypertensive patients free of prevalent cardiovascular (CV) diseases or severe chronic kidney disease and with at least 6-month follow-up from the Campania Salute Network. During 55±44 months of follow-up, incidence of ISH was 21%. Patients with ISH at the follow-up were significantly older (P<0.0001), had longer duration of hypertension, higher prevalence of diabetes and were more likely to be women (all P<0.0001). They exhibited higher baseline left ventricular mass index (LVMi), arterial stiffness (pulse pressure/stroke index), relative wall thickness (RWT) and carotid intima-media thickness (IMT; all P<0.001). Independent predictors of incident ISH were older age (odds ratio (OR)=1.14/5 years), female gender (OR=1.30), higher baseline systolic blood pressure (OR=1.03/5 mm Hg), lower diastolic blood pressure (OR=0.89/5 mm Hg), longer duration of hypertension (OR=1.08/5 months), higher LVMi (OR=1.02/5 g m−2.7), arterial stiffness (OR=2.01), RWT (OR=1.02), IMT (OR=1.19 mm−1; all P<0.0001), independently of antihypertensive treatment, obesity, diabetes and fasting glucose (P>0.05). Our findings suggest that ISH is a sign of aggravation of the atherosclerotic disease already evident by the target organ damage. Great efforts should be paid to prevent this evolution and prompt aggressive therapy for arterial hypertension should be issued before the onset of target organ damage, to reduce global CV risk.

Cardiovascular risk in subjects with left ventricular concentric remodeling: does meta-analysis help reconcile inconsistent findings?

Cardiovascular risk in subjects with left ventricular concentric remodeling: Does meta-analysis help reconcile inconsistent findings?

ASSOCIATION OF INSULIN RESISTANCE WITH PRECLINICAL CARDIOVASCULAR DISEASE IN ADOLESCENTS AND YOUNG ADULTS: THE STRONG HEART STUDY: 1C.01

Background: Insulin resistance is associated with unfavorable cardiovascular (CV) phenotype, but it is unclear whether this association is already recognizable in adolescents and young adults independently of significant confounders. Methods: We analyzed clinical characteristics, hemodynamic parameters, echocardiographic left ventricular (LV) geometry and function in 1688, 14 to 39 year-old non-diabetic participants in the 4th Strong Heart Study exam (mean age 26 ± 7.6, 57% female), without prevalent valvular or CV disease, divided into tertiles of insulin resistance, estimated by Homeostasis Model Assessment (HOMA). Comparison among the groups was obtained by ANCOVA, adjusting for major covariates. Multiple linear regression analysis was performed to evaluate factors associated with log HOMA. Results: Age, BMI, waist girth, waist-hip ratio (WHR), and systolic and diastolic BP progressively increased with tertiles of HOMA (all p < 0.0001). Compared to participants in the 2 lower HOMA tertiles, those in the 3rd tertile were more often obese (85% vs. 57% in the 2nd and 19% in the 1st tertile), more commonly had hypertension (21% vs. 12% and 12%), dyslipidemia (80% vs. 70% and 45%) and albuminuria (20% vs. 14% and 10, all p < 0.0001). After adjustment for age, gender, WHR, systolic BP and presence of hypertension, participants with higher level of HOMA index showed, compared to lower tertiles, progressively higher left atrial dimension, LV mass index (LVMi) and stroke volume (all p for trend < 0.05). In multiple linear regression logHOMA was independently related to age (β = 0.13), female gender (β = 0.28), WHR (β = 0.30), triglycerides (β = 0.18), HDL cholesterol (β = −0.18), systolic BP (β = 0.11) and LVMi (β = 0.17, all p < 0.0001) without significant relation to albumin/creatinine ratio. Compared to the 1st HOMA tertile, LV hypertrophy was associated with the higher HOMA tertiles (OR=3.15, CI:1.15–6,51 for the 2nd tertile; OR = 4.24, CI:2.04–8.81 for the 3rd tertile), independent of age, sex, WHR, systolic BP, hypertension and dyslipidemia. Conclusions: Despite the young age of participants, in a population with high prevalence of obesity, insulin resistance is associated with early metabolic abnormalities and preclinical CV disease.

NON INVASIVE EVALUATION OF MYOCARDIAL STIFFNESS IN ARTERIAL HYPERTENSION: PP.22.348

Background: Heart failure with preserved ejection fraction (HFPEF) is frequent in hypertension in the absence of preceding myocardial infarction and is attributed to abnormal myocardial stiffness (MS), altering the physiological pressure/volume relationship. A direct non-invasive measure of MS is still a challenge. Methods: Using standard transthoracic Doppler-echocardiography and tissue-Doppler, we generated a single point LV end-diastolic (ED) pressure (P)/volume (V) ratio as an estimate of MS in 59 normotensive and 64 hypertensive subjects (18–91 yrs). ED-P was calculated as LV pressure before atrial contraction (estimated by E/E’ ratio) + peak atrio-ventricular gradient at the atrial contraction (from peak A velocity). ED-P/V was 0.15 ± 0.05 in normotensive subjects and the value of 0.20 (90th percentile) defined increased MS. We also generated P/V loops for subjects with (n = 33) or without (n = 90) increased ED-P/V, by assuming: 1) P at mitral opening = 5 mmHg; 2) End of isometric contraction corresponding to aortic diastolic P; 3) Peak-systolic P = cuff systolic P occurring at 2/3 of LV empting; 4) End-systolic P estimated as: mean cuff P*0.98 + 11, corresponding to the time of end-systolic V. Results: Subjects with high ED-P/V (n = 33, 82% hypertensive) exhibited higher ejection fraction and relative wall thickness with lower midwall shortening, stroke volume and stroke work (see figure) than those with normal ED-P/V (all p < 0.0001) and similar LV mass. Conclusions: Thus, a CV phenotype at high risk of HFPEF corresponds to a high non-invasively determined single-beat ED-P/V ratio as an estimate of increased myocardial stiffness. This method might identify hypertensive patients at high risk of HFPEF. Figure 1. No caption available.

LEFT VENTRICULAR MASS, PUMP PERFORMANCE AND CARDIOVASCULAR EVENTS: THE STRONG HEART STUDY: PP.22.374

Background: Ejection-phase indices of LV function such as ejection fraction (EF) are strong prognostic indicators. However, at given level of EF, LV pump performance (stroke volume [SV]) may differ, depending on LV size. but, it is unknown whether low SV is a prognostic marker independent of its strong biological collinearity with high LV mass (LVM). We assessed the associations of EF, SV and LVM with cardiovascular (CV) events in a large population free of CV disease. Method: After the 2nd SHS exam, we examined 8-year outcome of quintiles of EF, SV (z-derived method) and LVM in 2323 participants (58 ± 7 yrs; 62% women) without prevalent coronary heart disease, stroke or heart failure (hypertension in 39%, diabetes in 45% and obesity in 54%). Results: In univariate Cox models, risk of composite fatal or non-fatal cardiovascular (CV) events increased across lower quintiles of EF (log rank = 21.7; p = 0.0002) and higher quintiles of LVM (log rank = 40.8; p < 0.00001). In contrast SV did not show significant predictive value. LVM was negatively related to EF (r = −0.37), but was positively correlated with SV (r = 0.66), (both p < 0.0001). Thus, the level of LVM, could confound evaluation of the association of SV with subsequent CV events. Thus, we evaluated LV pump performance per gram of LVM (SV/LVM). Kaplan Meier curves revealed a progressively higher rate of CV events with lower quintiles of SV/LVM (log Rank = 36.3; p < 0.0001). Cox regression, adjusting for age and sex and including EF, SV and LVM showed that hazard of incident CV events increased with higher LVM (HR = 1.1/10 g, CI = 1.05–1. 12, p < 0.0001) and lower SV (HR = 0.90/10 mL, CI = 0.80–0.98; p < 0.01), with no independent effect of EF (HR = 0.90/10%, CI = 0.70–1.03, p = 0.11). Conclusion: Evaluation of LV pump performance is influenced by the amount of myocardial muscle pumping blood into the arterial tree. When LV mass is taken into consideration, indices of LV pump performance may be at least as good as ejection-phase indices of LV function for identification of subjects at risk of incident CV events.

Preclinical Systolic Dysfunction in Patients With Stage 3 Chronic Renal Disease: Pp.9.376:

Background: Chronic kidney disease (CKD) is associated with increased cardiovascular (CV) risk. Cardiac abnormalities have been studied in severe CKD but not in the most prevalent stage 3 (s3), often under-diagnosed. We evaluated whether s3-CKD is associated with abnormalities of CV system. Methods: 39 asymptomatic patients with s3-CKD (GFR = 45 ± 10 ml/min/1.73m2), free of prevalent CV disease, from the outpatient clinic of the Department of Nephrology, were compared with 44 control subjects with GFR>60 ml/min/1.73m2 (GFR = 84 ± 14 ml/min/1.73m2) and comparable prevalence of hypertension (66% vs 69 in s3-CKD). In addition to standard echocardiographic parameters of left ventricular (LV) geometry and function, we computed non-invasive effective arterial elastance (EAe in mmHg/mL/beat, using an estimate of end-systolic pressure), systolic LV elastance (LVe, in mmHg/mL) and myocardial mechanic efficiency (MME, in mL/sec), using previously reported formulas. Results: s3-CKD and controls were comparable for age, sex, lipid profile, prevalence of diabetes and smoking habit. LV mass, LV geometry and stroke work were similar in the two groups, but both ejection fraction and midwall shortening (mS) were significantly reduced in s3-CKD (both p < 0.001), with 36% s3-CKD with clear-cut depressed mS. EAe and peripheral resistance were higher in s3-CKD than in controls (both p < 0.002), without significant difference in LVe, resulting in an apparently favorable vascular ventricular coupling. However MME was substantially reduced in CKD (p < 0.004). For comparable levels of LV mass, MME was substantially reduced in s3-CKD, compared to controls, with the difference increasing with increasing values of LV mass (p < 0.001 for slope). Similarly, at a given level of peripheral resistance, LV geometry was less concentric in s3-CKD than in controls (p < 0.05). Conclusions: We conclude that s3-CKD asymptomatic patients present with a peculiar CV phenotype, characterized by impaired mechano-energetic efficiency and reduced midwall mechanics, in the absence of compensating LV concentric remodeling, to avoid fall in ejection fraction. How much these characteristics might impact evolution toward more pronounced LV abnormalities in more advanced CKD and incident heart failure should be investigated.

INCREASED LEFT VENTRICULAR MASS IN HYPERTENSIVE MEN IS MORE STRONGLY RELATED TO CENTRAL THAN TO BRACHIAL BLOOD PRESSURE CONTROL: PP.3.99

Background: Cardiovascular risk in hypertension (HTN) has been shown to be more strongly related to central systolic blood pressure (c-SBP) than to brachial (cuff) systolic blood pressure (b-SBP). We examined the relation of left ventriculat (LV) mass and LV hypertrophy (H) with BP control defined by both b-SBP and c-SBP. Methods: Ninety-one patients without diabetes or prevalent cardiovascular disease (80% HTN, 42% men, 57 ± 15yrs), underwent standard 2D echocardiography and blood pressure measurement using a commercially available device (HEM-9000AI, Omron Healthcare Co., Kyoto, Japan). Central SBP was derived from the SBP2 peak according to a previously invasively validated equation. Results: Nine patients were excluded due to sinus arrhythmia or suboptimal BP curve recording. The remaining 82 patients (56 ± 15yrs, 27.7 ± 4.6Kg/m2; 65 HTN of which 72% treated) were dichotomized according to the presence of uncontrolled HTN (SBP ± 140mmHg) by b-SBP and by c-SBP.Higher prevalence of uncontrolled HTN was found when classification was made according to c-SBP (52.4%) as compared to b-SBP (41.5%; p < 0.001), with poor agreement between the two methods (kappa score = 0.54). Analysis of the whole population showed that uncontrolled HTN (by b-SBP or c-SBP) was associated with higher values of LV mass index and relative wall thickness (p < 0.01). However, in men (n = 37) classification by b-SBP was unable to identify differences among group with controlled vs. uncontrolled HTN in either LV mass or LVH prevalence (p = NS). In fact, classification based on c-SBP showed significantly higher values of LV mass index in patients with uncontrolled BP (43 ± 11 g/m2.7) compared to those with controlled BP (37 ± 8 g/m2.7). Figure 1. No caption available. Accordingly, prevalence of LVH was significantly higher in uncontrolled HTN when the classification was based on c-SBP (30 vs 6% p = 0.05). Conclusions: compared to b-SBP, c-SBP better identifies hypertensive men with increased LV mass and LVH, and may be of incremental value in risk stratification.