Effect of age on interdependence and hierarchy of cardiovascular risk factors in hypertensive patients

The prognostic significance, interdependence, and hierarchy of cardiovascular risk factors could evolve with advancing age. Our study reports on the interdependence among blood pressure (BP), other metabolic syndrome components, and high-sensitivity C-reactive protein according to age in hypertensive subjects. A total of 5,712 nondiabetic patients (50.1% men, age range 40 to 95 years) evaluated in outpatient hypertension clinics were included and divided into 5 age groups (age 40 to 49, 50 to 59, 60 to 69, 70 to 79, and >80 years). BP, evaluated by both office and 24-hour ambulatory BP monitoring, and the metabolic and inflammation parameters were determined after a ≥2-week drug washout period. The prevalence of the metabolic syndrome (Adult Treatment Panel III definition) remained stable across the age groups. We observed a stable or increased association between waist circumference and insulin resistance (Homeostasis Model of Assessment-Insulin Resistance index) and fasting plasma glucose. However, the association between waist circumference and ambulatory BP monitoring systolic BP (r(2) decrease from 9.9% to 1.0%, p <0.001), high-density lipoprotein cholesterol (r(2) decreased from 21% to 4.9%, p = 0.002), and triglyceride levels (r(2) decreased from 17.5% to 1.9%, p <0.001) decreased with age. High-sensitivity C-reactive protein correlated with all metabolic syndrome components in all age groups (p <0.001 for all). It became the strongest determinant of ambulatory BP monitoring systolic BP (p <0.001) and high-density lipoprotein cholesterol (p <0.05) in patients >80 years old. In contrast, its association with waist circumference markedly decreased. In conclusion, hypertension and dyslipidemia, but not fasting plasma glucose, dissociate from central obesity with advancing age. They are increasingly determined by low-grade inflammation, independently of central obesity. These changing associations might underlie the weakening of obesity as a cardiovascular risk factor in older persons.