SEVERAL EPIDEMIOLOGIC studies have shown that some major risk factors for atherosclerosis such as total cholesterol level and smoking status tend to lose their predictive power for morbidity and mortality in old age.^1-4 In recent years, evidence has been accumulating that high heart rate is an important risk factor for cardiovascular and noncardiovascular death in middle-aged^5-9 as well as in elderly^10,11 normotensive subjects. Much less is known about whether heart rate is a risk factor for mortality also in hypertensive individuals because only a few studies have examined this relationship in the hypertensive segment of 2 populations,^12,13 and to the best of our knowledge, no study has been conducted in elderly subjects with hypertension. Another point that needs to be clarified is whether there are sex differences in the impact of a potentially modifiable risk factor such as heart rate on mortality in hypertensive individuals. In the Framingham Study, a significant association between heart rate and mortality was found in men and women with hypertension.¹² In contrast, the more recent study by Benetos et al¹³ found a relationship between heart rate and mortality among men but not women with hypertension.

Objectives The longitudinal relationship between coffee use and hypertension is still controversial. Cytochrome P450 1A2 (CYP1A2) is the main responsible enzyme for the metabolism of caffeine. The aim of the present study was to investigate the effect of coffee intake on the risk of developing hypertension needing antihypertensive treatment in individuals stratified by CYP1A2 genotype. Design We assessed prospectively 553 young White individuals screened for stage 1 hypertension. Coffee intake was ascertained from regularly administered questionnaires. Incident physician-diagnosed hypertension was the outcome measure. Genotyping of CYP1A2 SNP was performed by real time PCR. Results During a median follow-up of 8.2 years, 323 individuals developed hypertension. For carriers of the slow *1F allele (59%), hazard ratios of hypertension from multivariable Cox analysis were 1.00 in abstainers (reference), 1.72 (95%CI, 1.21–2.44) in moderate coffee drinkers (P = 0.03), and 3.00 (1.53–5.90) in heavy drinkers (P = 0.001). In contrast, hazard ratios for coffee drinkers with the rapid *1A/*1A genotype were 0.80 (0.52–1.23, P = 0.29) for moderate drinkers and 0.36 (0.14–0.89, P = 0.026) for heavy drinkers. In a two-way ANCOVA, a gene × coffee interactive effect was found on follow-up changes in systolic (P = 0.000) and diastolic (P = 0.007) blood pressure. Urinary epinephrine was higher in coffee drinkers than abstainers but only among individuals with slow *1F allele (P = 0.001). Conclusion These data show that the risk of hypertension associated with coffee intake varies according to CYP1A2 genotype. Carriers of slow *1F allele are at increased risk and should thus abstain from coffee, whereas individuals with *1A/*1A genotype can safely drink coffee.

The association of ambulatory blood pressure (BP) variability with mortality and cardiovascular events is controversial. To investigate whether BP variability predicts cardiovascular events and mortality in hypertension, we analyzed 7112 untreated hypertensive participants (3996 men) aged 52±15 years enrolled in 6 prospective studies. Median follow-up was 5.5 years. SD of night-time BP was positively associated with age, body mass index, smoking, diabetes mellitus, and average night-time BP (all P <0.001). In a multivariable Cox model, night-time BP variability was an independent predictor of all-cause mortality (systolic, P <0.001/diastolic, P <0.0001), cardiovascular mortality ( P =0.008/<0.0001), and cardiovascular events ( P <0.001/<0.0001). In contrast, daytime BP variability was not an independent predictor of outcomes in any model. In fully adjusted models, a night-time systolic BP SD of ≥12.2 mm Hg was associated with a 41% greater risk of cardiovascular events, a 55% greater risk of cardiovascular death, and a 59% increased risk of all-cause mortality compared with an SD of <12.2 mm Hg. The corresponding values for a diastolic BP SD of ≥7.9 mm Hg were 48%, 132%, and 77%. The addition of night-time BP variability to fully adjusted models had a significant impact on risk reclassification and integrated discrimination for all outcomes (relative integrated discrimination improvement for systolic BP variability: 9% cardiovascular events, 14.5% all-cause death, 8.5% cardiovascular death, and for diastolic BP variability: 10% cardiovascular events, 19.1% all-cause death, 23% cardiovascular death, all P <0.01). Thus, addition of BP variability to models of long-term outcomes improved the ability to stratify appropriately patients with hypertension among risk categories defined by standard clinical and laboratory variables.