Blood Pressure Levels at the Time of Percutaneous Coronary Revascularization and Risk of Coronary In-Stent Restenosis.

BACKGROUND: High blood pressure (BP) levels expose patients treated with percutaneous coronary interventions (PCI) to very high risk of 10-year cardiovascular morbidity and mortality. OBJECTIVE: To investigate the role of BP levels at the time of PCI on the risk of in-stent restenosis (ISR). METHODS: We retrospectively included 796 patients previously treated with PCI, who underwent repeated angiography for recurrent angina or reversible myocardial ischemia. Patients were stratified into either case (n = 354) and control (n = 442) groups in the presence or absence of ISR (defined as in-stent diameter stenosis ≥50%). BP levels were measured at the time of first and second procedures. Normal BP levels were defined for <140/90 mm Hg. RESULTS: Patients with normal BP showed significantly higher ISR-free survival (Log-rank: 5.937; P = 0.015). Both systolic (HR (95% CI): 0.731 (0.590-0.906)) and systolic/diastolic BP (HR (95% CI): 0.757 (0.611-0.939)) were significantly and independently associated with lower risk of ISR at Cox-regression analysis, adjusted for potential confounding factors, including stent type and concomitant medications. Patients with ISR showed lower rates of normal systolic/diastolic BP values (166 (47%) vs. 254 (57%); P = 0.003) compared to controls. They also received higher stent number (1.40±0.74 vs. 1.24±0.51; P < 0.001) with higher stent length (24.3±15.6 vs. 21.7±13.9 mm; P = 0.012), and lower rate of drug-eluting stents (DESs) (210 (48%) vs. 139 (40%); P = 0.025) compared to controls. CONCLUSIONS: Normal BP at the time of PCI is associated with nearly 24% risk reduction of ISR as evaluated in a new angiography in patients with coronary artery disease.

P-wave duration in lead aVR and the risk of atrial fibrillation in hypertension.

BACKGROUND: Hypertension entails atrial remodeling that affect P-wave (PW) duration on electrocardiogram (ECG). PW indices (e.g., variance, dispersion, and terminal force) are associated with a higher risk for atrial fibrillation (AF), but their calculation requires multiple measurements of PW duration, limiting their use in clinical practice. We evaluated whether PW duration in specific ECG leads may identify patients with increased susceptibility to AF in a population of hypertensive patients. METHODS: In a case-control study, AF and control subjects were matched for age, sex, and left atrial (LA) dimensions. PW duration was measured from digitally stored ECGs. Logistic regression was used to assess the association of PW duration and indices with AF. RESULTS: We enrolled 44 hypertensive AF patients (16 paroxysmal and 28 persistent) and 44 hypertensive controls. AF and control subjects were matched for sex (males, n = 27), age (67 ± 8 years), LA diameter (40 ± 5 mm), and were comparable for left ventricular mass (45 ± 11 g/m(2.7) vs 48 ± 12 g/m(2.7) , P = 0.19), ejection fraction (58 ± 7% in both groups), and prevalence of mild valvular heart disease (7% vs 5%; P = 0.64). PW duration in lead aVR was significantly higher in AF patients as compared with controls (115 ± 18 ms vs 101 ± 14 ms; P < 0.0001) and was the best independent predictor of AF in multivariable logistic regression (PW ≥ 100 ms: RR = 3.7; 95% CI: 1.3-10.3; P = 0.02). CONCLUSIONS: Simple measurement of PW duration in lead aVR allows effective identification of AF patients in a population of hypertensives. Confirmation of this finding in a larger population would provide a simple and effective risk marker of AF in hypertensive patients.

Atrial natriuretic Peptide single nucleotide polymorphisms in patients with nonfamilial structural atrial fibrillation.

BACKGROUND: Atrial natriuretic peptide (ANP) has antihypertrophic and antifibrotic properties that are relevant to AF substrates. The -G664C and rs5065 ANP single nucleotide polymorphisms (SNP) have been described in association with clinical phenotypes, including hypertension and left ventricular hypertrophy. A recent study assessed the association of early AF and rs5065 SNPs in low-risk subjects. In a Caucasian population with moderate-to-high cardiovascular risk profile and structural AF, we conducted a case-control study to assess whether the ANP -G664C and rs5065 SNP associate with nonfamilial structural AF. METHODS: 168 patients with nonfamilial structural AF and 168 age- and sex-matched controls were recruited. The rs5065 and -G664C ANP SNPs were genotyped. RESULTS: The study population had a moderate-to-high cardiovascular risk profile with 86% having hypertension, 23% diabetes, 26% previous myocardial infarction, and 23% left ventricular systolic dysfunction. Patients with AF had greater left atrial diameter (44 ± 7 vs. 39 ± 5 mm; P < 0.001) and higher plasma NTproANP levels (6240 ± 5317 vs. 3649 ± 2946 pmol/mL; P < 0.01). Odds ratios (ORs) for rs5065 and -G664C gene variants were 1.1 (95% confidence interval [CI], 0.7-1.8; P = 0.71) and 1.2 (95% CI, 0.3-3.2; P = 0.79), respectively, indicating no association with AF. There were no differences in baseline clinical characteristics among carriers and noncarriers of the -664C and rs5065 minor allele variants. CONCLUSIONS: We report lack of association between the rs5065 and -G664C ANP gene SNPs and AF in a Caucasian population of patients with structural AF. Further studies will clarify whether these or other ANP gene variants affect the risk of different subphenotypes of AF driven by distinct pathophysiological mechanisms.

Depression treatment selectively modifies arterial stiffness in older participants.

BACKGROUND: Depression is emerging as an independent cardiovascular disease risk factor. We investigated whether treating depression in older participants impacted on arterial stiffness, a known cardiovascular disease risk factor and a clinical marker of arterial aging. METHODS: Seventy-five participants with pulse wave velocity (PWV), the gold standard measure for arterial stiffness, at baseline and at 12-month follow-up were included. Depressed patients were randomized to escitalopram (10mg/d) or to duloxetine (60mg/d). In patients without depression, no antidepressant therapy was started. The psychologist and the doctor measuring PWV were both unaware of antidepressant treatment. RESULTS: At study entry, no difference in PWV were observable in the three groups of participants. A significant time × drug interaction term (p < .05) was observed for the impact of antidepressant therapy on PWV by analysis of covariance analysis. After 12 months of therapy, duloxetine treatment resulted in a significant (+21%) and escitalopram treatment in a not significant (6%) PWV increase. These changes in PWV were accompanied by a similar increase in blood pressure and LDL cholesterol in the two treated groups. However, duloxetine resulted in a significant 10% greater heart rate after 12 months that was not observable in participants treated with escitalopram nor in not-depressed older participants. Multiple regression models revealed that a drug-specific effect on PWV persisted after controlling for cardiovascular risk factor levels. CONCLUSION: Duloxetine but not escitalopram significantly increased PWV in older depressed participants after 12 months of treatment. The effect was not fully explained by concomitant changes in traditional cardiovascular risk factors known to significantly impact arterial stiffness.

Occurrence of hypotension in older participants. Which 24-hour ABPM parameter better correlate with?

OBJECTIVES: The aim of the present study was to investigate the prevalence of hypotension in older participants and to identify which 24-hour ambulatory blood pressure monitoring parameter better correlated with the occurrence of hypotension. METHODS: We studied 588 elderly participants (mean age 78.7 ± 7.1 years; 70% women) who underwent a 24-hour ambulatory blood pressure (BP) monitoring, without moderate-to-severe cognitive impairment, myocardial infarction, or stroke within the previous 6 months; renal (serum creatinine > 2.5 mg/dL), respiratory, or liver insufficiency; and atrial fibrillation. RESULTS: In older participants, the occurrence of systolic hypotension is very common (≈55% presenting at least one episode of systolic blood pressure (SBP) < 100 mmHg and about 20% presenting ≥10% of the SBP registrations < 100 mmHg). More than 30% of participants with 24-hour SBP, daytime, and nighttime above the reference threshold had hypotension. Hypotension did not correlated with BP variability indices (standard deviation of BPs). None of the parameters commonly present in 24-hour ambulatory BP monitoring clinical reports is able to accurately identify those older participants with episode of hypotension. CONCLUSION: Episodes of SBP hypotension are extremely common in older participants and do not appear to relate to BP variability indices. Indeed, no parameter of 24-hour ambulatory BP monitoring was capable to accurately identify the occurrence of hypotension. We expect that ongoing studies will contribute to identification of specific factors predicting hypotensive episodes in the older participants.

Plasma osteopontin reveals left ventricular reverse remodelling following cardiac resynchronization therapy in heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) promotes left ventricular (LV) reverse remodelling and affects myocardial collagen turnover in heart failure (HF) patients. Osteopontin (OPN) is a matrix glycoprotein required for the activation of fibroblasts upon TGF-ß1 stimulation. In humans, plasma OPN and OPN-expressing lymphocytes correlate with the severity of HF. We sought to evaluate whether plasma OPN and TGF-ß1 reflect LV reverse remodelling following CRT. METHODS: Eighteen patients (12 men, mean age 65 ± 11 years) undergoing CRT were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma OPN and TGF-ß1. The evaluation was repeated 8.5 ± 4 months after device implantation. Eight healthy age- and sex-matched subjects served as controls. RESULTS: In HF patients, baseline plasma OPN and TGF-ß1 were higher as compared to control subjects (OPN: 99 ± 48 vs 59 ± 22 ng/ml; p<0.05; TGF-ß1: 15.9 ± 8.0 vs 9.3 ± 5.6 ng/ml; p<0.05). At follow-up, 12 patients responded to CRT and showed LV reverse remodelling, whereas 6 did not. Plasma OPN decreased in CRT responders (108 ± 47 vs 84 ± 37 ng/ml; p=0.03) and increased in non-responders (79 ± 58 vs 115 ± 63 ng/ml; p<0.01). TGF-ß1 showed a trend towards reduction in responders (17.5 ± 8.7 vs 10.2 ± 8.9 ng/ml; p=0.08) and was unchanged in non-responders. A significant correlation (r=-0.56; p=0.01) was found between relative changes of LVESV and plasma OPN. CONCLUSIONS: CRT-induced LV reverse remodelling is reflected by changes in plasma OPN. Circulating OPN may represent a marker of LV dilation/impairment and an indicator of the response to HF therapies promoting LV reverse remodelling.

Decreased nocturnal systolic blood pressure fall in older subjects with depression.

Depressed subjects have a two-fold increased risk of CV events than non-depressed ones. Altered blood pressure (BP) circadian profile may be one mechanism underlying this association. We studied 135 elderly subjects (mean age 78+/-6 yrs, range 69- 93; 30 M, 87 F). On the basis of the 15-items Geriatric Depression Scale (GDS), score>5 identified subjects with depressive symptoms. Based upon 24-h Ambulatory BP Monitoring (Spacelabs 90207), the following BP circadian profile measures were examined: SD of 24-h, day, and night SBP, DBP, MBP; 24-h, day, and night SBP and DBP load; night SBP and DBP decline; dipping status for SBP and DBP. Compared with non-depressed subjects (n=61), depressed subjects (n=74) were similar in age and more likely to be women. No significant differences in traditional CV risk factors or in medication use were observed between the two groups. After controlling for age, sex, and traditional CV risk factors, subjects with depressive symptoms presented a significantly lower night-time SBP fall than non-depressed ones (average, -4.4 mmHg for SBP) with a significantly higher occurrence of non-dipper status. The GDS score was an independent significant inverse determinant of 24-h SD of SBP. Depressive symptoms in older subjects are accompanied by lower nocturnal BP fall and are significant independent determinants of SBP variability.

Extracellular matrix remodelling in myocardial hypertrophy and failure : focus on osteopontin.

Cardiac remodelling refers to molecular and cellular changes of the myocardium, as well as adapting alterations in size, shape and function of the heart in response to changing loading conditions. It represents the final common pathway of different heart diseases, and is recognized as a crucial aspect of cardiac and myocardial dysfunction and a well established determinant of the clinical course of heart failure.Osteopontin is an extracellular matrix glycoprotein secreted by osteoblasts, osteoclasts, macrophages, T cells, vascular smooth muscle cells, fibroblasts and cardiomyocytes. Osteopontin is not expressed in healthy cardiac tissue, although its expression can be triggered by pressure or volume overload, hypoxia and angiotensin II. Indeed, osteopontin has been reported in macrophages and interstitial tissues early after myocardial infarction and in cardiac macrophage-like cells of inflammatory lesions in experimental models of cardiomyopathy. Pressure overload is associated with osteopontin overexpression as well. Indeed, myocardial osteopontin messenger RNA is upregulated in rats following renovascular hypertension or aortic banding. In humans, a significant correlation exists between increased osteopontin immunoreactivity in cardiac myocytes and impaired left ventricular function or cardiomyocyte hypertrophy in patients with dilated cardiomyopathy.The present article focuses on the role of osteopontin in myocardial hypertrophy and remodelling. In general, evidence supports the concept that osteopontin plays a crucial role in extracellular matrix remodelling following myocardial adaptation to hypertrophic, inflammatory and neurohormonal stimuli in the overloaded heart.