Abstract-Increased arterial stiffness has been shown to predict cardiovascular mortality in patients with primary hypertension. Asymptomatic organ damage is known to precede cardiovascular events. We investigated the relationship between a recently proposed index of stiffness derived from ambulatory blood pressure (BP) and target organ damage in 188 untreated patients with primary hypertension. Ambulatory arterial stiffness index was defined as 1 minus the regression slope of diastolic over systolic BP readings obtained from 24-hour recordings. Albuminuria was measured as the albumin:creatinine ratio, left ventricular mass index was assessed by echocardiography, and carotid abnormalities were evaluated by ultrasonography. The prevalence of microalbuminuria, left ventricular hypertrophy (LVH), and carotid abnormalities was 12%, 38%, and 19%, respectively. Ambulatory arterial stiffness index was positively related to age, triglycerides, office and 24-hour systolic BP, 24-hour pulse pressure, urinary albumin excretion, and carotid intima-media thickness. Patients with microalbuminuria, carotid abnormalities, or LVH showed higher ambulatory arterial stiffness index as compared with those without it. After adjusting for confounding factors, each SD increase in ambulatory arterial stiffness index entails an Ϸ2 times higher risk of microalbuminuria, carotid abnormalities, and LVH and doubles the risk of the occurrence of Ն1 sign of organ damage. Ambulatory arterial stiffness index is associated with organ damage in patients with primary hypertension. These data strengthen the role of this index as a marker of risk and help to explain the high cardiovascular mortality reported in patients with high ambulatory arterial stiffness index. (Hypertension. 2006;48:397-403.)

Abstract-The role of serum uric acid as an independent risk factor for cardiovascular and renal morbidity is controversial.A better understanding of its relationship with preclinical organ damage may help clarify the mechanism(s) implicated in the development of early cardiovascular disease. We evaluated the association between uric acid and the presence and degree of target organ damage in 425 (265 males, 160 females) middle-aged, untreated patients with essential hypertension. Left ventricular mass index and carotid intima-media thickness were assessed by ultrasound scan. Albuminuria was measured as the albumin to creatinine ratio in 3 nonconsecutive first morning urine samples. Overall, patients with target organ damage had significantly higher levels of serum uric acid as compared with those without it (presence versus absence of left ventricular hypertrophy, Pϭ0.04; carotid abnormalities, PϽ0.05; microalbuminuria, PϽ0.004; and at least 1 versus no organ damage, PϽ0.03). In women, the occurrence and severity of each target organ damage we examined increased progressively from the lower to the upper serum uric acid tertiles (PϽ0.01). After adjustment for body mass index, age, creatinine clearance, and high-density lipoprotein cholesterol, each standard deviation increase in serum uric acid entailed a 75% higher risk of having cardiac hypertrophy and a 2-times greater risk of having carotid abnormalities. These results support the role of serum uric acid as an independent, modifiable marker of cardiovascular damage.

Objectives To describe clinical characteristics, management and outcome of individuals with coronavirus disease 2019 (COVID-19); and to evaluate risk factors for all-cause in-hospital mortality. Methods This retrospective study from a University tertiary care hospital in northern Italy, included hospitalized adult patients with a diagnosis of COVID-19 between 25 February 2020 and 25 March 2020. Results Overall, 317 individuals were enrolled. Their median age was 71 years and 67.2% were male (213/317). The most common underlying diseases were hypertension (149/317; 47.0%), cardiovascular disease (63/317; 19.9%) and diabetes (49/317; 15.5%). Common symptoms at the time of COVID-19 diagnosis included fever (285/317; 89.9%), shortness of breath (167/317; 52.7%) and dry cough (156/317; 49.2%). An ‘atypical’ presentation including at least one among mental confusion, diarrhoea or nausea and vomiting was observed in 53/317 patients (16.7%). Hypokalaemia occurred in 25.8% (78/302) and 18.5% (56/303) had acute kidney injury. During hospitalization, 111/317 patients (35.0%) received non-invasive respiratory support, 65/317 (20.5%) were admitted to the intensive care unit (ICU) and 60/317 (18.5%) required invasive mechanical ventilation. All-cause in-hospital mortality, assessed in 275 patients, was 43.6% (120/275). On multivariable analysis, age (per-year increase OR 1.07; 95% CI 1.04–1.10; p < 0.001), cardiovascular disease (OR 2.58; 95% CI 1.07–6.25; p 0.03), and C-reactive protein levels (per-point increase OR 1.009; 95% CI 1.004–1.014; p 0.001) were independent risk factors for all-cause in-hospital mortality. Conclusions COVID-19 mainly affected elderly patients with predisposing conditions and caused severe illness, frequently requiring non-invasive respiratory support or ICU admission. Despite supportive care, COVID-19 remains associated with a substantial risk of all-cause in-hospital mortality.

Organ damage (OD) is an indicator of increased cardiovascular risk. Blood pressure variability (BPV) is related to greater incidence of events, regardless of the severity of hypertension. We investigated the relationship between ambulatory blood pressure monitoring (ABPM)-derived indices of BPV and the presence of multiple OD in primary hypertension (PH). One hundred and sixty-nine untreated patients with PH were evaluated. Systolic (SBP) and diastolic blood pressure (DBP) variability were assessed as the crude and weighted (w.) standard deviation (s.d.), and average real variability (ARV) of the mean value of 24-h, awake and asleep ABPM recordings. Left ventricular mass index, intima-media thickness, estimated-glomerular filtration rate and urinary albumin excretion were assessed as indices of cardiac, vascular and renal damage, respectively. Risk profile progressively increased starting from patients without OD to patients with only one sign of OD, and then to those with multiple OD. In addition to greater severity of the organ involvement, the only variables that were found to significantly differ between subjects with multiple and single OD were office SBP (160 ± 14 vs 154 ± 11 mm  Hg, P=0.0423) and DBP (101 ± 7 vs 97 ± 8  mm Hg, P=0.0291), ambulatory arterial stiffness index (AASI) (0.60 ± 0.10 vs 0.50 ± 0.17, P=0.0158) and indices of BPV (24-h SBP s.d., 23 ± 5 vs 20 ± 6  mm  Hg, P=0.0300; awake SBP s.d., 22 ± 6 vs 19 ± 6  mm  Hg, P=0.0366; 24-h SBP w.s.d., 20 ± 5 vs 17 ± 5  mm  Hg, P=0.0385; and 24-h SBP ARV, 18 ± 4 vs 15 ± 5  mm  Hg, P=0.0420). All the above mentioned BPV parameters turned out to be determinants of multiple OD, regardless of several confounding variables, including BP levels. Therefore, in hypertensive patients increased SBP variability is associated with multiple signs of OD, regardless of BP values.

Abstract. Leoncini G, Ratto E, Viazzi F, Vaccaro V, Parodi D, Parodi A, Falqui V, Tomolillo C, Deferrari G, Pontremoli R (University of Genoa, Genoa, Italy). Metabolic syndrome is associated with early signs of organ damage in nondiabetic, hypertensive patients. J Intern Med 2005; 257: 454-460.Objectives. Hypertensive patients with metabolic syndrome (MS) are at greater risk for cardiovascular disease. To get a better understanding of the pathophysiology underlying this association, we evaluated the relationship between MS and subclinical organ damage in essential hypertensive patients. Design and setting. A total of 354 untreated, nondiabetic patients with primary hypertension were included in the study. A modified ATP III definition for MS was used, with body mass index replacing waist circumference. Albuminuria was measured as albumin to creatinine ratio, left ventricular mass index (LVMI) was assessed by echocardiography and carotid abnormalities by ultrasonography.Results. The prevalence of MS was 25%. Patients with MS were more likely to be smokers (P ¼ 0.004) and had higher serum uric acid levels (P ¼ 0.004). Moreover, they showed higher urinary albumin excretion (P ¼ 0.0004) and LVMI (P ¼ 0.0006), increased intima-media thickness (P ¼ 0.045), as well as higher prevalence of microalbuminuria (P ¼ 0.03) and left ventricular hypertrophy (LVH; P ¼ 0.003). After adjusting for age, gender and duration of hypertension, we found that the presence of MS entails a twofold greater risk for microalbuminuria (P ¼ 0.04), LVH (P ¼ 0.003) and carotid abnormalities (P < 0.05). When patients were stratified according to the number of components of MS, albuminuria (P ¼ 0.002) and LVMI (P ¼ 0.005) increased progressively across categories. Conclusions. Metabolic syndrome is associated with subclinical organ damage in nondiabetic, essential hypertensive patients. These data may, in part, explain the high cardiovascular morbidity and mortality that is observed in hypertensive patients with MS.

Hypertensive patients with microalbuminuria show a higher prevalence of unfavourable left ventricular geometric patterns, depressed left ventricular function and early signs of extra-cardiac vascular damage. These findings strengthen the role of microalbuminuria as an indicator of subclinical cardiovascular disease and may account for the worse outcome that is usually associated with increased urinary albumin excretion in essential hypertension.

Objectives: Previous studies suggested that vitamin D modulates circulating IGF1. We investigated this effect in adults and its clinical relevance in the management of GH deficiency (GHD). Design and methods: IGF1 levels were prospectively measured before and after 12 weeks of treatment with oral vitamin D 3 (5000 or 7000 IU/week) vs no intervention in 39 subjects 61.9G7.9 years old. The frequency of IGF1 values R50th age-and sex-specific percentile in relation to vitamin D status, as determined by the concentration of 25-hydroxyvitamin D (25(OH)D), was retrospectively assessed in 69 GHD patients (57.4G16.6 years) on stable hormone replacement and with 25(OH)D and IGF1 concurrently measured. Results: Treatment with 5000 and 7000 IU vitamin D 3 /week significantly raised 25(OH)D by 12.7G8.4 and 13.1G6.5 ng/ml respectively (both P!0.001 vs baseline). In the 7000 IU group, IGF1 levels also significantly increased by 31.3G36.7 ng/ml (PZ0.01). Neither 25(OH)D nor IGF1 significantly varied in controls. IGF1 was R50th percentile more frequently in GHD patients with 25(OH)D levels R15 than !15 ng/ml (65.9 vs 40.0%, P!0.05). Logistic regression with adjustment for recombinant human GH (rhGH) dose, vitamin D supplements, gender, use of thyroid hormones, corticosteroids or estrogen/testosterone, and season revealed a significant positive association between R15 ng/ml 25(OH)D and IGF1 R50th percentile (OR 4.4, 95% CI 1.0-18.8, P!0.05). A significant negative correlation between 25(OH)D concentrations and rhGH dose was found after correcting for age and IGF1 (b K0.042, P!0.01), but not after further adjusting for sex, thyroid, adrenal or gonadal replacement, and season (b K0.037, PZ0.06). Conclusions: Vitamin D increases circulating IGF1 in adults. As a result, a better vitamin D status may ease the achievement of normal IGF1 values in GHD.

A significant inter-arm difference in systolic blood pressure (IADSBP) has been recently associated with worse cardiovascular outcomes. We hypothesized that part of this association is mediated by arterial stiffness, and examined the relationship between significant IADSBP and carotid-femoral pulse wave velocity (CF-PWV) in a sample from the Baltimore Longitudinal Study of Aging. Of 1045 participants, 50 (4.8%) had an IADSBP≥10 mmHg at baseline, and 629 had completed data from two or more visits (for a total of 1704 visits across 8 years). CF-PWV was significantly higher in those with an IADSBP≥10 mmHg (7.3±1.9 vs. 8.2±2, p=0.002). Compared to others, those with IADSBP≥10 mmHg had also higher body mass index, waist circumference and triglycerides, higher prevalence of diabetes and lower HDL-cholesterol (p<.001 for all). A significant association with IADSBP≥10 mmHg was observed for CF-PWV in both cross-sectional (OR=1.19; 95%CI: 1.06–1.87; p=0.01) and longitudinal (OR=1.15; 95%CI: 1.03–1.29; p=0.01) multivariate analyses. Female gender, Caucasian race, high body mass index (plus diabetes and low HDL-cholesterol only cross-sectionally) were other independent correlates of IADSBP≥10 mmHg. In conclusion, significant IADSBP is associated with increased arterial stiffness in community-dwelling older adults.